Hormonal Contraceptives

Overview

Components

Hormonal contraceptives (HCs) contain synthetic analogs of the reproductive hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones. HCs may contain either:

Progestin + estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy
Progestin alone

Choice of contraception

The choice of contraceptive method is very individual and often is dictated by a variety of factors, including:

Ease of access and use (e.g., dosing regimen, required procedures)
Affordability
Efficacy rate
Reversibility or permanence
Prevention of STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs)
Adverse effects
Medical contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

Comparison of the effectiveness of hormonal and nonhormonal contraceptive methods
Image by Lecturio.

Chemistry

Both estrogens and progestins are steroid hormones Steroid hormones Steroid hormones produced by the gonads. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include estradiol; progesterone; and testosterone. Hormones: Overview and Types, making them fat-soluble.

Ethinyl estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins (EE):

Very similar in structure to natural estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins
Addition of an ethynyl group makes it significantly more stable (i.e., steric hindrance resists metabolic degradation) than estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins.
↑ Bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics as compared with estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins when taken orally
EE is the most common estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy used in HCs, but newer formulations include:
- Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins valerate (with dienogest)
- 17-beta estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins (with nomegestrol acetate)
- Estetrol (with drospirenone)

Chemical structure of estradiol
Image: “chemical structure of Estradiol” by Klaus Hoffmeier. License: Public Domain

Ethinyl estradiol — Chemical structure of estradiol
Image: “chemical structure of Estradiol” by Klaus Hoffmeier. License: Public Domain

Progestins:

Similar in structure to natural progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones
Addition of a triple bond in most cases makes the molecules more stable.
Androgenic effects:
- Most are derived from testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens → have stronger androgenic effects than natural progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones
- Major exception: drospirenone
  - Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics analog
  - Has antiandrogenic activity
Multiple different progestins are used in HCs → different properties of the progestins are responsible for different side-effect profiles of various HCs

Pharmacodynamics

Normal physiology of the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle

Understanding hormonal regulation of ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle and the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle is key to understanding the mechanisms of HCs. This regulation is primarily by the hypothalamic-pituitary-ovarian (HPO) axis.

HPO axis HPO axis Gonadal Hormones:
- Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus secretes gonadotropin-releasing hormone Gonadotropin-releasing hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Gnrh is produced by neurons in the septum preoptic area of the hypothalamus and released into the pituitary portal blood, leading to stimulation of gonadotrophs in the anterior pituitary gland. Puberty (GnRH).
- Pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types secretes:
  - Follicle-stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle)
  - Luteinizing hormone ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle)
- Ovary secretes:
  - Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy
  - Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones
Follicular/ proliferative phase Proliferative phase Menstrual Cycle (1st phase of menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle):
- GnRH pulse stimulates the release of FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle.
- FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle stimulates follicular development within the ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy.
- Developing follicles produce estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy, specifically estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins.
- Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy:
  - Stimulates endometrial proliferation
  - Inhibits FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle secretion Secretion Coagulation Studies (feedback inhibition)
  - Stimulates bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types growth
Ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle:
- Triggered by a midcycle surge of LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
Luteal/ secretory phase Secretory phase Menstrual Cycle:
- The ovulated follicle is now called the corpus luteum Corpus Luteum The yellow body derived from the ruptured ovarian follicle after ovulation. The process of corpus luteum formation, luteinization, is regulated by luteinizing hormone. Ovaries: Anatomy.
- The corpus luteum Corpus Luteum The yellow body derived from the ruptured ovarian follicle after ovulation. The process of corpus luteum formation, luteinization, is regulated by luteinizing hormone. Ovaries: Anatomy produces both estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones.
- Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones:
  - Stabilizes endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development
  - Causes endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development to mature into secretory endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development, capable of sustaining a pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  - Study tip: progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones = “progestational hormone” → produced only after ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle, when gestation is possible
- Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones are secreted for approximately 14 days after ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle (time for a fertilized embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week to implant).
- If pregnant: corpus luteum Corpus Luteum The yellow body derived from the ruptured ovarian follicle after ovulation. The process of corpus luteum formation, luteinization, is regulated by luteinizing hormone. Ovaries: Anatomy continues producing progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones until the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity can take over.
- If not pregnant: corpus luteum Corpus Luteum The yellow body derived from the ruptured ovarian follicle after ovulation. The process of corpus luteum formation, luteinization, is regulated by luteinizing hormone. Ovaries: Anatomy involutes → estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins and progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones levels fall
Menstrual phase:
- Loss of stabilizing hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types (particularly progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones) triggers breakdown of the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development → menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
- Key point: Progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones withdrawal triggers bleeding.

Correlation-between-the-ovarian-cycle-and-the-endometrial-cycle — Diagram showing the correlation between the ovarian cycle and the endometrial cycle
Image by Lecturio.

Mechanism of action of hormonal contraceptives

Both estrogens and progestins cause an antiovulatory effect. When used together, this effect is synergistic.

Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy component:
- Inhibits FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle release → prevents the selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions and maturation of the dominant follicle Dominant follicle Menstrual Cycle = no ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
- Would stimulate endometrial proliferation if given alone/without progestins (this is why EE is not given alone)
Progestin component:
- Inhibits LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle surge that is necessary for ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
- Effects on the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development:
  - Natural progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones is required to make the endometrium Endometrium The mucous membrane lining of the uterine cavity that is hormonally responsive during the menstrual cycle and pregnancy. The endometrium undergoes cyclic changes that characterize menstruation. After successful fertilization, it serves to sustain the developing embryo. Embryoblast and Trophoblast Development healthy for pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care; however, the androgenic nature of synthetic progestins thins the endometrial lining, making it unsuitable for implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week.
  - All HCs are “progestin-dominant” as compared to estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy → overall endometrial effect of HCs is endometrial atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
- ↑ Cervical mucus viscosity → inhibits sperm transport into the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Uterus, Cervix, and Fallopian Tubes: Anatomy
- ↓ Cilia motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility in the fallopian tube Fallopian Tube A pair of highly specialized canals extending from the uterus to its corresponding ovary. They provide the means for ovum transport from the ovaries and they are the site of the ovum’s final maturation and fertilization. The fallopian tube consists of an interstitium, an isthmus, an ampulla, an infundibulum, and fimbriae. Its wall consists of three layers: serous, muscular, and an internal mucosal layer lined with both ciliated and secretory cells. Uterus, Cervix, and Fallopian Tubes: Anatomy

Classification

Hormonal contraceptives can be grouped by the length of their action and route of administration. These contraceptives are then classified in different ways, including by their components and dosages.

Short-acting contraceptives

This category includes pills, patches Patches Vitiligo, rings, and injections. Several common combinations and brand names in each category are given as examples, though there are many different brand names for each.

Combined oral contraceptive Oral contraceptive Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors pills (COCP; EE + progestin):
- Daily administration
- Classification by progestin:
  - 1st generation (estranes): EE/ norethindrone Norethindrone A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. Noncontraceptive Estrogen and Progestins acetate
  - 2nd generation (gonanes): EE/norgestrel, EE/levonorgestrel
  - 3rd generation: EE/desogestrel, EE/norgestimate
  - 4th generation/unclassified: EE/drospirenone (e.g., Yaz^®)
- Classification by number of “phases”:
  - Monophasic: Each pill in the pack contains the same amount of hormone.
  - Triphasic: The amount of hormone varies from pill to pill in the pack.
  - Many different EE/progestin combinations can come in both monophasic and triphasic packs.
Progestin-only pills (POPs):
- Daily administration
- Timing critical: ≤3 hours late ( norethindrone Norethindrone A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. Noncontraceptive Estrogen and Progestins), backup contraception if late
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  - Norethindrone Norethindrone A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. Noncontraceptive Estrogen and Progestins 0.35 mg: Cervical mucus mechanism, 30-40% still ovulate
  - Drospirenone 4 mg (Slynd): Suppresses ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle, more effective
  - Norgestrel 0.075 mg (Opill): OTC, suppresses ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle
Transdermal patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes:
- Weekly application for 3 weeks (i.e., 1 patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes applied per week), followed by 1 patch-free week
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  - EE/norelgestromin (Xulane): 35 mcg EE + 150 mcg norelgestromin daily
  - EE/levonorgestrel (Twirla): 30 mcg EE + 120 mcg LNG daily
- Contraindication: BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥30 kg/m² (both patches Patches Vitiligo)
- VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk: May be higher than oral contraceptives due to 60% higher EE exposure
Vaginal ring:
- Monthly application (3 weeks in, 1 week out)
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  - ENG/EE ring (NuvaRing): Monthly use, 120 mcg ENG + 15 mcg EE daily
  - SA/EE ring (Annovera): Yearly use, 150 mcg SA + 13 mcg EE daily
- Advantage: Lower estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy exposure than equivalent-dose oral contraceptives
- Side effects: More vaginal symptoms (vaginitis, discharge)
Progestin contraceptive injections:
- “Quarterly” administration (i.e., 1 injection every 3 months)
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types: depot medroxyprogesterone acetate (DMPA, e.g., Depo-Provera^®)

Birth control patch — Illustration showing the site of placement of the transdermal patch and the extent of penetration of drugs into the layers of the skin
Image by Lecturio.

Vaginal ring — Illustration showing the site of placement of the transdermal patch and the extent of penetration of drugs into the layers of the skin
Image by Lecturio.

Long-acting reversible contraceptives (LARCs)

Subdermal contraceptive implants (etonogestrel implant):
- Nexplanon^®: lasts 3 years
Intrauterine device (IUDs): levonorgestrel IUDs
- Mirena^®, Liletta^® (52 mg of levonorgestrel): last 5–7 years
- Kyleena^® (19.5 mg of levonorgestrel): lasts 5 years
- Skyla^® (13.5 mg of levonorgestrel): lasts 3 years

Intrauterine devices — Site of placement of the subdermal implant
Image by Lecturio.

Emergency contraception

Refers to contraception administered after unprotected intercourse (UPI; called “the morning after pill”). These options act to prevent fertilization Fertilization To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. Fertilization and First Week and/or implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week and are not used as postimplantation abortifacients.

Insertion of an IUD:
- More effective than oral methods
- Provide ongoing contraception
- Not impacted by BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity or risk of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care (e.g., UPI midcycle, multiple episodes of UPI)
- Options:
  - Copper IUD Copper IUD Intrauterine contraceptive devices that depend on the release of metallic copper. Nonhormonal Contraception (Paragard^®)
  - Levonorgestrel 52-mg IUD
Oral methods:
- Less effective in individuals with BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity > 30
- Less effective in individuals at higher risk of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
- Options:
  - Ulipristal Ulipristal Antiprogestins and Selective Progesterone Modulators acetate (can be used up to 5 days after UPI)
  - Oral levonorgestrel (can be used up to 3 days after UPI)

Pharmacokinetics

Methods of administration

Hormone-free interval:
- Pills/ patches Patches Vitiligo/rings containing hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types are typically used for 21–24 days in a row ( ovulation Ovulation The discharge of an ovum from a rupturing follicle in the ovary. Menstrual Cycle and endometrial growth are suppressed during this time).
- This is followed by a hormone-free interval (HFI):
  - Typically 4–7 days in length
  - Pill packs include placebo Placebo Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. Epidemiological Studies pills during the HFI; the patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes/ring is withheld during this time.
  - Withdrawal of the progestin triggers a withdrawal bleed (similar to menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle), which is why skipping pills can lead to irregular bleeding.
Cyclic administration:
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types taken for 21–24 days followed by 4–7-day HFI
- Results in monthly withdrawal bleeding
Prolonged cyclic administration:
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types taken for up to 84 days (12 weeks) followed by a 4–7-day HFI
- Results in withdrawal bleeding only during the HFIs (typically 4 times per year)
- Some brands are designed this way, though any monophasic pill, the patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, and the ring can be used this way.
- Hormone use can be extended beyond 12 weeks if tolerated by the patient.
Continuous administration:
- Hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types are taken continuously, with no HFI.
- Monophasic pills, the patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, and vaginal ring can all be administered this way.
- Completely suppresses menstruation Menstruation The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle and symptoms associated with hormone fluctuations (e.g., menstrual migraines)
- Higher risk of breakthrough bleeding owing to prolonged endometrial atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
Emergency contraception:
- Taken as a single course as soon as possible after UPI
- Specific regimens depend on days from UPI and medications/methods chosen.

Ethinyl Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
- Rapid absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption via any route (e.g., oral, topical, and vaginal)
- Oral bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics: approximately 50% ( estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins is only approximately 5%)
Distribution:
- Highly protein-bound: approximately 98% (primarily albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests; unlike estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins, EE does not bind BIND Hyperbilirubinemia of the Newborn well to sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria hormone–binding globulin ( SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones))
- Steroid hormones Steroid hormones Steroid hormones produced by the gonads. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include estradiol; progesterone; and testosterone. Hormones: Overview and Types → distributed throughout the body
Metabolism:
- High 1st-pass metabolism (though significantly less than for estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins)
- Conjugated via glucuronidation and sulfation to inactive metabolites
- Also hydroxylated via CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers)
- Enterohepatic recirculation occurs
Excretion:
- Oral half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics: approximately 10–16 hours
- Fecal: 60%
- Urine: 40%

Progestins

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
- High oral bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics
- IUD components have low (but some) systemic absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption.
- LARCs secrete decreasing amounts of progestins daily the longer they are in place.
Distribution:
- Highly protein-bound
- Some bind BIND Hyperbilirubinemia of the Newborn more to albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests; others bind BIND Hyperbilirubinemia of the Newborn more to SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones.
Metabolism:
- Most undergo 1st-pass hepatic metabolism to inactive metabolites.
- Some are metabolized by the CYP450 system.
- Enterohepatic recirculation can occur.
Excretion:
- In both urine and feces
- Oral half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics: approximately 20–40 hours

Indications

Contraception
Abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding (e.g., heavy, prolonged, or frequent bleeding)
- Good options:
  - COCPs/ patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes/ring
  - Levonorgestrel IUDs
- Generally avoided owing to higher risks of abnormal bleeding:
  - POPs
  - DMPA
  - Etonorgestrel implant
Dysmenorrhea and/or endometriosis Endometriosis Endometriosis is a common disease in which patients have endometrial tissue implanted outside of the uterus. Endometrial implants can occur anywhere in the pelvis, including the ovaries, the broad and uterosacral ligaments, the pelvic peritoneum, and the urinary and gastrointestinal tracts. Endometriosis
Polycystic ovarian syndrome Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome
Premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis ovarian insufficiency (i.e., premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause)
Other specific indications:
- Menstrual symptoms (especially menstrual migraines and premenstrual syndrome Premenstrual Syndrome A combination of distressing physical, psychologic, or behavioral changes that occur during the luteal phase of the menstrual cycle. Symptoms of pms are diverse (such as pain, water-retention, anxiety, cravings, and depression) and they diminish markedly 2 or 3 days after the initiation of menses. Premenstrual Dysphoric Disorder (PMS)): continuous COCPs/ patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes/ring
- Hirsutism Hirsutism A condition observed in women and children when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated androgens from the ovaries, the adrenal glands, or exogenous sources. The concept does not include hypertrichosis, which is an androgen-independent excessive hair growth. Polycystic Ovarian Syndrome: COCPs containing the antiandrogenic progestin drospirenone
- Endometrial hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation: levonorgestrel 52-mg IUDs

Adverse Effects and Contraindications

Adverse effects

Most of the adverse effects can be seen with either EE or progestins and are possible with any of the HC methods.

Risk of venous thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus ( VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States):
- Oral contraceptives: 3-5x increased relative risk Relative risk Relative risk (RR) is the risk of a disease or condition occurring in a group or population with a particular exposure relative to a control (unexposed) group. Measures of Risk, 0.06 per 100 pill-years absolute risk Absolute risk The AR is the risk of developing a disease or condition after an exposure. Measures of Risk
- Patches Patches Vitiligo: May have modestly higher VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk than oral contraceptives
- Rings: Similar VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk to oral contraceptives
- POPs: No increased VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk
Abnormal bleeding (e.g., unscheduled bleeding, prolonged bleeding)
- Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy tends to stabilize bleeding patterns, so this is more often associated with progestin-only methods
- Worst with etonogestrel implant
Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
Acne
Headaches/migraines
Mood changes
Decreased libido
Altered lipid metabolism Lipid Metabolism Lipid metabolism is the processing of lipids for energy use, energy storage, and structural component production. Lipid metabolism uses fats from dietary sources or from fat stores in the body. A complex series of processes involving digestion, absorption, and transport are required for the proper metabolism of lipids. Lipid Metabolism and insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin effects
Breast symptoms:
- Fibrocystic Fibrocystic Fibrocystic Change breast changes
- Mastalgia (breast pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways), especially cyclic
- Decreased breast milk production during breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding (EE only)
Ovarian cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change (progestin-only methods, since EE generally suppresses cyst formation)
Unique adverse effects:
- Vaginal ring: ↑ vaginal discharge
- DMPA injections: bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types loss (reversible)
- Implant: high association with irregular bleeding as compared with other methods
- IUDs:
  - Pelvic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  - Endometritis Endometritis Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. Postpartum Endometritis
  - Uterine perforation Perforation A pathological hole in an organ, blood vessel or other soft part of the body, occurring in the absence of external force. Esophagitis
  - If pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care occurs, significantly ↑ risk of that pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care being ectopic (though the absolute rate of ectopic pregnancy Ectopic pregnancy Ectopic pregnancy refers to the implantation of a fertilized egg (embryo) outside the uterine cavity. The main cause is disruption of the normal anatomy of the fallopian tube. Ectopic Pregnancy is lower in IUD users than in individuals on no contraception)

Drug interactions of combined oral contraceptive Oral contraceptive Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors pills and progestin-only pills

The metabolism of COCP and POPs is increased by any drugs that increase liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy microsomal enzyme activity, resulting in reduced contraceptive efficacy. These drugs include:

Anticonvulsants:
- Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
- Carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs
- Barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics
- Topiramate Topiramate A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of epilepsy and migraine disorders, and may also promote weight loss. Second-Generation Anticonvulsant Drugs
- Felbamate Felbamate A pegylated phenylcarbamate derivative that acts as an antagonist of nmda receptors. It is used as an anticonvulsant, primarily for the treatment of seizures in severe refractory epilepsy. Second-Generation Anticonvulsant Drugs
- Oxcarbazepine Oxcarbazepine A carbamazepine derivative that acts as a voltage-gated sodium channel blocker. It is used for the treatment of partial seizures with or without secondary generalization. It is also an inducer of cytochrome p-450 cyp3a4. First-Generation Anticonvulsant Drugs
- Lamotrigine Lamotrigine A phenyltriazine compound, sodium and calcium channel blocker that is used for the treatment of seizures and bipolar disorder. Second-Generation Anticonvulsant Drugs (HC retains efficacy but concentrations of lamotrigine Lamotrigine A phenyltriazine compound, sodium and calcium channel blocker that is used for the treatment of seizures and bipolar disorder. Second-Generation Anticonvulsant Drugs are ↓ )
Antimicrobials:
- Reduce efficacy: Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis, rifabutin Rifabutin A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. Diseases of the Uvea, enzyme-inducing anticonvulsants
- No interaction: Most antibiotics ( amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins, azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides, doxycycline)
- Patches Patches Vitiligo: May have fewer interactions due to avoiding first-pass metabolism
Antiretroviral drugs
- Nonnucleoside reverse transcriptase inhibitors Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (rna-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. Anti-HIV Drugs (e.g., efavirenz Efavirenz Anti-HIV Drugs)
- Protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs (e.g., ritonavir Ritonavir An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits cytochrome p-450 cyp3a. Anti-HIV Drugs)

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

The “Summary Chart of U.S. Medical Eligibility Criteria for Contraceptive Use” by the Centers for Disease Control and Prevention (CDC) notes the specific risks of each contraceptive method and > 100 different conditions. This document is a critical resource when determining the safety of a particular method for a specific individual. The most important contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation are noted below.

EE-containing HCs (COCPs/ patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes/ring):

Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
Current, history of, or risk factors for, VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States, including:
- < 21 days postpartum
- Certain coagulopathies Coagulopathies Hemothorax
- Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus)
Cardiovascular disease:
- Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
- Ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
- Peripartum cardiomyopathy Peripartum cardiomyopathy Dilated Cardiomyopathy
- Valvular heart disorders with complications
Migraines with aura Aura Reversible neurological phenomena that often precede or coincide with headache onset. Migraine Headache
Undiagnosed abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding ( AUB AUB Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym palm-coein, with palm representing the structural causes and coein indicating the non-structural causes. Abnormal Uterine Bleeding)
Current or past breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer
Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease, including:
- Decompensated liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
- Hepatocellular adenoma Hepatocellular adenoma A benign epithelial tumor of the liver. Benign Liver Tumors
- Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cancer
Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus > 20 years or with vascular disease ( neuropathy Neuropathy Leprosy, nephropathy, retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome)
Hypertriglyceridemia Hypertriglyceridemia A condition of elevated levels of triglycerides in the blood. Lipid Disorders
Solid-organ transplantation with complications
Category 3 (risks usually outweigh benefits):
- Age ≥35 + smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases <15 cigarettes/day
- Controlled hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (140-159/90-99 mmHg)
Category 4 (unacceptable risk):
- Age ≥35 + smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases ≥15 cigarettes/day
- Systolic BP ≥160 or diastolic ≥100 mmHg
- Current VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States, migraine with aura Migraine with Aura A subtype of migraine disorder, characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision; hallucinations; vertigo; numbness; and difficulty in concentrating and speaking. Aura is usually followed by features of the common migraine, such as photophobia; phonophobia; and nausea. Migraine Headache
- Current breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer, decompensated cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
Method-specific contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
- Both patches Patches Vitiligo: BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥30 kg/m² contraindicated
- POPs (fewer contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation): Current/history breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer, undiagnosed AUB AUB Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym palm-coein, with palm representing the structural causes and coein indicating the non-structural causes. Abnormal Uterine Bleeding, severe liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease

Progestin-only HCs:

Generally preferred methods in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at risk for VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States. Beyond that, contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation are similar to EE-containing HCs and include:

Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
Current or past breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer
Undiagnosed AUB AUB Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym palm-coein, with palm representing the structural causes and coein indicating the non-structural causes. Abnormal Uterine Bleeding
Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
Additional contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation specific to IUDs:
- Uterine anomalies
- Pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease ( PID PID Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and gardnerella vaginalis. Pelvic Inflammatory Disease) or endometritis Endometritis Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. Postpartum Endometritis
- Acute cervicitis Cervicitis Inflammation of the uterine cervix. Gonorrhea or vaginitis (e.g., Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia or bacterial vaginosis Bacterial vaginosis Polymicrobial, nonspecific vaginitis associated with positive cultures of gardnerella vaginalis and other anaerobic organisms and a decrease in lactobacilli. It remains unclear whether the initial pathogenic event is caused by the growth of anaerobes or a primary decrease in lactobacilli. Vulvovaginitis infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease at the time of planned IUD insertion)

Special Populations

Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity ( BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥30 kg/m²):
- Oral contraceptives: Generally safe, Category 2
- Patches Patches Vitiligo: Contraindicated (both types)
- Rings: Limited data, Category 2
- POPs: Not contraindicated, efficacy concerns
Postpartum/ Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding:
- Combined methods: Delay until 21+ days postpartum
- POPs: Can start immediately, safe during breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Cardiovascular risk factors:
- Combined methods: Avoid if multiple risk factors
- POPs: Safe option for estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation
Adolescents:
- All methods: Appropriate after menarche Menarche The first menstrual cycle marked by the initiation of menstruation. Menstrual Cycle
- Consider: Compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology with daily methods (POPs, oral contraceptives)

Comparison of Different Contraceptive Methods

**Table: Comparison of different contraceptive methods**
Method	Failure Rates – Perfect/Typical Use	Key Features	Major Advantages	Major Disadvantages
Combined oral contraceptives	0.3%/7%	Daily dosing	High degree of control, well-tolerated	Daily compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology required, VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk
Transdermal patches Patches Vitiligo	0.3%/7%	Weekly dosing	Less frequent dosing	BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity ≥30 contraindicated, may have higher VTE VTE Obstruction of a vein or veins (embolism) by a blood clot (thrombus) in the bloodstream. Hypercoagulable States risk
Vaginal rings	0.3%/7-9%	Monthly dosing	Lower estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy exposure, superior cycle control	More vaginal symptoms, insertion required
Progestin-only pills	0.7-4%/>7%	Daily dosing, strict timing	Safe in estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation	Higher failure rate, irregular bleeding
Levonorgestrel IUDs	<1%/<1%	3-7 years	Highly effective, reduces bleeding	Requires procedure, upfront cost
Copper IUD Copper IUD Intrauterine contraceptive devices that depend on the release of metallic copper. Nonhormonal Contraception	<1%/<1%	10-12 years	Hormone-free, longest duration	Heavier periods, requires procedure

References

Allen, R. H. (2024, Apr 22). Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use. UpToDate. Retrieved June 30, 2025, from https://www.uptodate.com/contents/combined-estrogen-progestin-oral-contraceptives-patient-selection-counseling-and-use
Roe, A., et al. (2023, Oct 23). Combined estrogen-progestin oral contraceptives: Side effects and health concerns. UpToDate. Retrieved June 30, 2025, from https://www.uptodate.com/contents/combined-estrogen-progestin-contraception-side-effects-and-health-concerns
Kaunitz, A. M. (2025, Mar 17). Contraception: Progestin-only pills (POPs). UpToDate. Retrieved June 30, 2025, from https://www.uptodate.com/contents/progestin-only-pills-pops-for-contraception
Kaunitz, A. M. (2024, May 21). Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits. UpToDate. Retrieved June 30, 2025, from https://www.uptodate.com/contents/depot-medroxyprogesterone-acetate-dmpa-efficacy-side-effects-metabolic-impact-and-benefits
Kaunitz, A. M. (2025, Jun 12). Depot medroxyprogesterone acetate (DMPA): formulations, patient selection, and drug administration. UpToDate. Retrieved June 30, 2025, from https://www.uptodate.com/contents/depot-medroxyprogesterone-acetate-dmpa-formulations-patient-selection-and-drug-administration
Darney, P. D. (2024, Sep 12). Contraception: Etonogestrel implant. UpToDate. Retrieved June 30, 2025, from https://www.uptodate.com/contents/etonogestrel-contraceptive-implant
Casey, F. E. (2023, Aug). Oral contraceptives. MSD Manual Professional Version. Retrieved June 30, 2025, from https://www.msdmanuals.com/professional/gynecology-and-obstetrics/family-planning/oral-contraceptives
Casey, F. E. (2023, Aug). Progestin contraceptive injections. MSD Manual Professional Version. Retrieved June 30, 2025, from https://www.msdmanuals.com/professional/gynecology-and-obstetrics/family-planning/progestin-contraceptive-injections
Casey, F. E. (2023, Aug). Subdermal contraceptive implants. MSD Manual Professional Version. Retrieved June 30, 2025, from https://www.msdmanuals.com/professional/gynecology-and-obstetrics/family-planning/subdermal-contraceptive-implants
Casey, F. E. (2023, Oct). Intrauterine devices (IUDs; IUD). MSD Manual Professional Version. Retrieved June 30, 2025, from https://www.msdmanuals.com/professional/gynecology-and-obstetrics/family-planning/intrauterine-device-iuds-iud
Cason, P., Cwiak, C., Edelman, A., Kowal, D., Hatcher, R. A., Nelson, A. L., Trussell, J., Policar, M. S., Aiken, A. R. A., & Marrazzo, J. (2023). Contraceptive technology (22nd ed.). Jones & Bartlett Learning.
Curtis, K. M., Tepper, N. K., Jatlaoui, T. C., Berry-Bibee, E., Horton, L. G., Zapata, L. B., Simmons, K. B., Pagano, H. P., Jamieson, D. J., & Whiteman, M. K. (2024). U.S. Selected Practice Recommendations for Contraceptive Use, 2024. MMWR Recommendations and Reports, 73(3), 1-77. https://doi.org/10.15585/mmwr.rr7303a1
Genazzani, A. R., Monteleone, P., Giannini, A., Simoncini, T., Stomati, M., & Luisi, M. (2023). Hormonal and natural contraceptives: A review on efficacy and risks of different methods for an informed choice. Gynecological Endocrinology, 39(1), 2247093. https://doi.org/10.1080/09513590.2023.2247093
Jahanfar, S., Lim, R., Costanian, C., Zelek, S. T., Barrowman, N., & El-Chaâr, D. (2024). Assessing the impact of contraceptive use on reproductive cancer risk among women of reproductive age—A systematic review. Frontiers in Global Women’s Health, 5, 1487820. https://doi.org/10.3389/fgwh.2024.1487820
Nguyen, A. T., Curtis, K. M., Tepper, N. K., Berry-Bibee, E., Zapata, L. B., Simmons, K. B., Moskosky, S., & Whiteman, M. K. (2024). U.S. Medical Eligibility Criteria for Contraceptive Use, 2024. MMWR Recommendations and Reports, 73(4), 1-66. https://doi.org/10.15585/mmwr.rr7304a1
Skeith, L., Carrier, M., Douketis, J., Desjardins, L., Lazo-Langner, A., Rodger, M., Kovacs, M. J., Wells, P. S., Anderson, D. R., Chagnon, I., Le Gal, G., Solymoss, S., Crowther, M., White, R., Ramsay, T., & Rodger, M. A. (2021). Oral contraceptives and hormone replacement therapy: How strong a risk factor for venous thromboembolism? Thrombosis Research, 202, 134-138. https://doi.org/10.1016/j.thromres.2021.03.012

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Overview

Components

Choice of contraception

Chemistry

Pharmacodynamics

Mechanism of action of hormonal contraceptives

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Classification

Short-acting contraceptives

Long-acting reversible contraceptives (LARCs)

Emergency contraception

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Pharmacokinetics

Methods of administration

Ethinyl Estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins

Progestins

Indications

Adverse Effects and Contraindications

Adverse effects

Drug interactions of combined oral contraceptive Oral contraceptive Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both. Benign Liver Tumors pills and progestin-only pills

Comparison of Different Contraceptive Methods

References

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