Androgens and Antiandrogens

Androgens are naturally occurring steroid 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 responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens are primarily given to treat hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism, gender dysphoria in transgender men, and low testosterone in older men (controversial). Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5α-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer Prostate cancer Prostate cancer is one of the most common cancers affecting men. In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, and the lifetime risk of death is 2.5%. Prostate cancer is a slow-growing cancer that takes years, or even decades, to develop into advanced disease. Prostate Cancer, benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. Benign Prostatic Hyperplasia (BPH), alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia, and hirsutism.

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Androgens

Definition

Androgens are 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, which lead to the development and maintenance of male sex characteristics. 

Endogenous androgens

Androgens are produced naturally in the gonads (testes and 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) and the adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands. The naturally produced androgenic 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 include:

  • Testosterone:
    • The major male androgen 
    • Produced by the testes:
      • 95% produced by Leydig cells
      • 5% produced by adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands
  • Dihydrotestosterone (DHT):
    • A more potent agonist relative to testosterone
    • Synthesized from testosterone by 5ɑ-reductase
  • Weaker androgens (produced in the adrenal glands Adrenal Glands The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. Adrenal Glands):
    • Androstenedione
    • Dehydroepiandrosterone (DHEA)
Overview of steroidogenesis pathways

Overview of steroidogenesis pathways

Image by Lecturio.

Medications in the drug class

  • Testosterones: 
    • Testosterone
    • Testosterone cypionate
    • Testosterone enanthate
    • Testosterone undecanoate
    • Methyltestosterone 
  • Anabolic steroids:
    • Stanozolol
    • Oxandrolone

Pharmacodynamics and mechanism of action

  • Produced from cholesterol
  • Act intracellularly on target cells
  • Bind to androgen receptors 
  • Lead to growth, differentiation, and synthesis of enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes and proteins resulting in androgenic effects
  • Converted to 5α-DHT by the enzyme 5α-reductase in DHT-sensitive tissues:
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin/hair follicles
    • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands 
    • Epididymis 
    • Seminal vesicle 

Physiologic effects

The physiologic effects of endogenously produced androgens and medications are identical and include:

  • General tissue growth
  • Penile and scrotal growth (men)
  • Clitoral enlargement (women)
  • Development of sexual hair: 
    • Pubic hair
    • Axillary hair
    • Facial hair (i.e., a beard)
  • Sebaceous glands become more active.
  • Deepening of the voice due to growth of the larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx and thickening of the vocal cords 
  • ↑ Lean body mass
  • Skeletal growth and an increase in 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. Structure of Bones mineral density
  • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands growth 
  • Stimulation and maintenance of sexual function in men
  • 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 synthesis of:
    • Triglyceride lipase
    • Clotting factors
    • Haptoglobin
  • Stimulation of renal erythropoietin (EPO) secretion → ↑ hematocrit

Pharmacokinetics

  • Administration: 
    • Oral (less effective)
    • IM
    • SC
    • Transdermal:
      • Patches
      • Gels
  • Absorption: 
    • Rapid 
    • Transdermal gels can rub off onto a partner causing effects (e.g., female partner may develop hirsutism).
  • Distribution: Circulating testosterone is primarily bound to sex hormone-binding globulin (SHBG) and albumin.
  • Metabolism: 
    • Undergoes extensive hepatic metabolism
    • Converted to inactive metabolites 
    • Oral formulations undergo extensive 1st-pass metabolism, which explains the lower effectiveness.
    • IM and transdermal formulations bypass 1st-pass metabolism → can be given in lower doses
    • Can be converted to estrogens by aromatase in peripheral adipose and hepatic tissue and have feminizing effects (e.g., gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia)
  • Excretion: urine  

Indications

  • Hypogonadism (insufficient natural production) due to:
    • Testicular disease (primary)
    • Dysfunction in the hypothalamic-pituitary-testicular (HPT) axis (secondary)
  • Gender dysphoria/transgender men
  • Constitutional delay of growth and puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty
  • Controversial/other reasons individuals use androgens:
    • Hormone replacement therapy (HRT) in older men with low testosterone (controversial medical indication)
    • Anabolic steroids and androgen abuse in sports for performance enhancement (not a medical indication, but frequently used/abused)

Adverse effects

  • Hepatic effects:
    • Cholestatic jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
    • Transaminitis
    • Hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases
  • Lipid, hematologic, and cardiovascular effects:
    • 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
    • Sodium retention and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema 
    • Dyslipidemia:
      • Hyperlipidemia
      • ↓ HDL cholesterol
      • ↑ Serum triglycerides
    • ↑ Hematocrit
    • ↑ Production of clotting factors 
    • ↑ Risk of: 
      • Atherosclerotic and cardiovascular disease
      • Venous thromboembolism (VTE) (relatively rare)
  • Dermatologic effects:
    • Acne
    • Irritation from topical applications (e.g., erythema, pruritus, contact dermatitis)
  • Nausea
  • Behavioral effects:
    • ↑ Aggression 
    • Psychotic symptoms
  • Women may experience:
    • Hirsutism 
    • Amenorrhea 
    • Clitoral enlargement 
    • Deepening of the voice
  • Men may experience:
    • Sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep apnea 
    • Gynecomastia
    • Testicular effects (due to suppression of natural testosterone production via feedback inhibition in the HPT axis):
      • Azoospermia → infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
      • ↓ Testicular size
    • Priapism (prolonged erection)
    • ↑ Risk of prostate cancer Prostate cancer Prostate cancer is one of the most common cancers affecting men. In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, and the lifetime risk of death is 2.5%. Prostate cancer is a slow-growing cancer that takes years, or even decades, to develop into advanced disease. Prostate Cancer
  • Additional effects of anabolic steroids:
    • Tendon rupture
    • Necrotizing fasciitis Necrotizing fasciitis Necrotizing fasciitis is a life-threatening infection that causes rapid destruction and necrosis of the fascia and subcutaneous tissues. Patients may present with significant pain out of proportion to the presenting symptoms and rapidly progressive erythema of the affected area. Necrotizing Fasciitis and myositis (may be fatal)

Contraindications

  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care 
  • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands cancer (some individuals may need antiandrogen therapy)
  • 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
  • Infants and young children 
  • Use with caution: 
    • Renal, hepatic, and cardiac disease
    • Benign prostatic hyperplasia (BPH)

Antiandrogens

Definition

Antiandrogenic medications block the action of androgens.

Classification, mechanism of action, and indication

Antiandrogens are generally classified according to the mechanism of action.

Table: Classification and mechanism of action of antiandrogens
Class Drugs in the class Mechanism of action Notes
Androgen receptor antagonists
  • Flutamide*
  • Bicalutamide
  • Nilutamide
Blocks androgen receptors via competitive inhibition Use of flutamide is more limited due to relatively higher toxicity; newer agents are typically preferred.
Spironolactone* Blocks aldosterone and androgen receptors via competitive inhibition Diuretic activity
5α-reductase inhibitors
  • Finasteride*
  • Dutasteride
Blocks conversion of testosterone to dihydrotestosterone (DHT) via competitive inhibition of type II 5α-reductase
  • Effects are only seen in DHT-sensitive tissues:
    • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands
    • Hair follicles
  • Testosterone levels are preserved.
Androgen synthesis inhibitors Ketoconazole* Inhibits 17ɑ-hydroxylase and 17,20-lyase ( enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes required for androgen synthesis) Significant antifungal activity
*Indicates the prototypical drug in the class

Pharmacokinetics

Table: Pharmacokinetics of antiandrogens
Drug Absorption Distribution Metabolism Excretion
Flutamide Rapid and complete PB: approximately 95% Extensive hepatic metabolism to multiple metabolites
  • Primarily urine
  • t1/2: approximately 6 hours
Spironolactone Bioavailability ↑ with fat PB: > 90% Extensive hepatic metabolism to multiple active metabolites
  • Primarily urine
  • t1/2: 1–2 hours
Finasteride Bioavailability: approximately 60% PB: 90% Extensive hepatic metabolism via CYP3A4 to active metabolites
  • Fecal: 60%
  • Urine: 40%
  • t1/2: 5–8 hours
Ketoconazole Bioavailability ↑ in acidic environments (decreases with antacids)
  • PB: 99%
  • Accumulates in fatty tissue
  • Partial hepatic metabolism via CYP3A4 to inactive metabolites
  • Strong inhibitor of CYP3A4
  • Fecal: approximately 60%
  • Urine: approximately 15%
  • t1/2 is biphasic:
    • Initial: 1‒2 hours
    • Terminal: 8 hours
PB: protein binding
t1/2: half-life

Indications

  • Summary of indications: 
    • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands cancer
    • BPH
    • Alopecia (i.e., male pattern baldness)
    • Acne
    • Gender dysphoria (transgender women)
  • Flutamide: advanced prostate cancer Prostate cancer Prostate cancer is one of the most common cancers affecting men. In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, and the lifetime risk of death is 2.5%. Prostate cancer is a slow-growing cancer that takes years, or even decades, to develop into advanced disease. Prostate Cancer 
  • Spironolactone: 
    • Antiandrogenic indications (primarily in women):
      • Hirsutism
      • Androgen suppression in transgender women
      • Acne
    • Antimineralocorticoid indications:
      • Heart failure
      • Primary hyperaldosteronism Hyperaldosteronism Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis. Hyperaldosteronism
      • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites due to 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
  • Finasteride: 
    • BPH
    • Alopecia
    • Hirsutism
    • Alternative agent for androgen suppression in transgender women (less desirable because non-testosterone blocking)
  • Ketoconazole:
    • Fungal infections
    • Advanced prostate cancer Prostate cancer Prostate cancer is one of the most common cancers affecting men. In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, and the lifetime risk of death is 2.5%. Prostate cancer is a slow-growing cancer that takes years, or even decades, to develop into advanced disease. Prostate Cancer
    • Cushing syndrome

Adverse effects

  • Gynecomastia and/or breast tenderness
  • Erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction
  • ↓ Libido
  • Depression 
  • Hot flashes
  • Menstrual irregularities in women
  • Hepatic toxicity 
  • GI distress (e.g., nausea, vomiting, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
  • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
  • Additional adverse effects of ketoconazole:
    • Adrenal suppression (high doses of ketoconazole)
    • QT prolongation

Contraindications

  • Acute or chronic liver disease
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Spironolactone: 
    • Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia
    • Addison disease
    • Renal insufficiency
  • Flutamide: women

Drug interactions

  • Ketoconazole: 
    • Drugs metabolized by CYP3A4
    • Many drug-to-drug interactions
  • Spironolactone: interaction with certain drugs causes an ↑ in serum potassium:
    • Amiloride
    • Cyclosporine 
    • Triamterene 
    • Eplerenone (a selective mineralocorticoid receptor blocker in the same class of diuretics as spironolactone)

Comparison Table

Table: Comparison between androgens and antiandrogens
Androgens Antiandrogens
Mechanism
  • Act intracellularly on target cells
  • Bind to and stimulate androgen receptors
Mechanisms include:
  • Inhibition of the androgen receptor
  • Inhibition of 5ɑ-reductase
  • Inhibition of androgen synthesis
Indications
  • Hypogonadism
  • Transgender men
  • Low testosterone
  • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands cancer
  • BPH
  • Alopecia
  • Hirsutism
  • Transgender women
Side effects
  • 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 disease
  • Dyslipidemia
  • Edema
  • Hirsutism
  • Acne
  • ↑ Aggression
  • Women:
    • Amenorrhea
    • Clitoral enlargement
    • Deepening of the voice
  • Men:
    • Gynecomastia
    • Azoospermia
    • ↓ Testicular size
  • Gynecomastia
  • Hepatic toxicity
  • Sexual dysfunction
  • Depression
  • Hot flashes
  • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
Contraindications
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Breast or prostate cancer Prostate cancer Prostate cancer is one of the most common cancers affecting men. In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, and the lifetime risk of death is 2.5%. Prostate cancer is a slow-growing cancer that takes years, or even decades, to develop into advanced disease. Prostate Cancer
  • Infants and young children
  • Acute or chronic liver disease
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Spironolactone: hyperkalemia

References

  1. Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic & Clinical Pharmacology (12th ed.). McGraw-Hill Education.
  2. Medical Students, Medscape (2021). Medscape. https://www.medscape.com/medicalstudents
  3. Sizar, O., & Pico, J. (2021). Androgen Replacement. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved October 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK534853/
  4. Nassar, G. N., & Leslie, S. W. (2021). Physiology, Testosterone. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved October 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK526128/
  5. Johnson, D. B., & Sonthalia, S. (2021). Flutamide. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved October 7, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482215/
  6. Lexicomp Drug Information Sheets (2021). In UpToDate. Retrieved October 7, 2021, from:

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