Premature Ovarian Failure – Top USMLE Diseases

Klinefelter syndrome is a chromosomal aneuploidy characterized by the presence of 1 or more extra X chromosomes in a male karyotype, most commonly leading to karyotype 47,XXY. Klinefelter syndrome is associated with decreased levels of testosterone and is the most common cause of congenital hypogonadism. Symptoms are often not noticed until adolescence or adulthood. Individuals with this condition tend to present as tall, phenotypic men with small testes, decreased body hair, gynecomastia, and infertility. Treatment consists of life-long testosterone replacement therapy.

Primary ovarian insufficiency (POI) is a condition resulting from the depletion or dysfunction of the ovarian follicles, leading to cessation of ovulation and menses before age 40. Primary ovarian insufficiency is primarily idiopathic, but it can also be seen in association with chromosomal and genetic defects, including Turner syndrome (45,X karyotype) and FMR1 premutation. Patients present with signs and symptoms of menopause prior to age 40, including oligomenorrhea or amenorrhea, vaginal dryness (often leading to dyspareunia), and infertility. Key laboratory findings include elevated follicle-stimulating hormone (FSH) and low estrogen levels. Once the diagnosis of POI is made, the patient should be screened for autoimmune adrenal antibodies, and a karyotype, FMR1 premutation screen, and baseline DEXA scan should be obtained. Management includes hormone replacement therapy (HRT), addressing fertility concerns as desired, and psychological support.

Androgen insensitivity syndrome (AIS) is an X-linked recessive condition in which a genetic mutation affects the function of androgen receptors, resulting in complete (CAIS), partial (PAIS), or mild (MAIS) resistance to testosterone. All individuals with AIS have a 46,XY karyotype; however, phenotypes vary and include phenotypic female, virilized female, undervirilized male, and phenotypic male individuals. Androgen insensitivity syndrome always leads to infertility. Hormone analysis, imaging, and genetic testing help make the diagnosis. Management of AIS varies depending on the degree of androgen sensitivity, phenotype, and gender identity, and may involve hormone-replacement therapy and surgery to correct anatomical anomalies of the reproductive and genital structures.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%‒10% of women in the age group. Characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction, PCOS increases a woman’s risk for infertility, endometrial hyperplasia or carcinoma, and cardiovascular disease. The pathophysiology is incompletely understood but thought to have a multifactorial genetic basis causing altered pulsatile release of gonadotropin-releasing hormone (GnRH), as well as increases in luteinizing hormone (LH), androgens, estrogen, and insulin: The result is chronic anovulation and hirsutism, which define the condition. Diagnosis is one of exclusion; therefore, other causes of abnormal uterine bleeding and hirsutism must be ruled out. Management includes attempting to restore normal ovulation through weight loss, oral contraceptive pills (OCPs), and fertility assistance.