Primary ovarian insufficiency

Menopause is the permanent cessation of menses from ovarian follicular depletion, confirmed retrospectively after 12 months of amenorrhea around a mean age of 51 years. Management centers on treating moderate to severe vasomotor symptoms with the lowest effective dose of hormone therapy in appropriately selected candidates, alongside bone and cardiovascular risk assessment.

Turner syndrome is a 45,X (or mosaic-variant) chromosomal disorder causing gonadal dysgenesis, short stature, and a characteristic phenotype including webbed neck, coarctation of the aorta, and horseshoe kidney. Karyotype confirms the diagnosis, and management centers on growth hormone in childhood and estrogen-based pubertal induction with lifelong cardiovascular and metabolic surveillance.

Secondary amenorrhea is absence of menses for 3 months in a woman with prior regular cycles or 6 months with prior irregular cycles, worked up stepwise with beta-hCG, TSH, prolactin, and a progesterone challenge test, then treated with the cause-specific therapy (cyclic progestin, dopamine agonist, thyroid replacement, or estrogen replacement).

Primary amenorrhea is the absence of menses by age 15 years with normal growth and secondary sexual development, or by age 13 years without it, and is worked up by a fixed algorithm that branches on secondary sexual characteristics, uterine presence, and gonadotropin level, then treated by cause with titrated estrogen replacement, surgery, or dilators. Genetic and anatomic causes account for the great majority of cases, led by gonadal dysgenesis (Turner syndrome) and mullerian agenesis.

Functional hypothalamic amenorrhea is a diagnosis of exclusion caused by stress, weight loss, or excessive exercise disrupting pulsatile GnRH secretion, producing hypogonadotropic hypogonadism with low LH, FSH, and estradiol; first-line treatment is increasing caloric intake and reducing exercise, with transdermal estrogen-progestin replacement added if menses do not return after 6 to 12 months.

Osteoporosis is low bone strength that raises fragility fracture risk, diagnosed by a hip or spine T-score of -2.5 or less or by a fragility fracture itself. First-line treatment is an oral bisphosphonate, alendronate or risedronate, alongside adequate calcium and vitamin D intake.

Infertility is failure to conceive after 12 months of regular, unprotected intercourse (6 months if the woman is 35 or older), most often from ovulatory dysfunction, male factor, or tubal or pelvic disease. Diagnosis rests on midluteal progesterone, semen analysis, and hysterosalpingography in both partners concurrently. First-line treatment for anovulatory infertility is ovulation induction with letrozole or clomiphene citrate, escalating to intrauterine insemination or in vitro fertilization when indicated.

Autoimmune polyglandular syndrome type 1 (APS-1, also called APECED) is caused by mutation of the AIRE gene, which normally drives thymic negative selection against self-reactive T cells; loss of AIRE produces the classic triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. Management is component-specific and lifelong: fluconazole for candidiasis, calcium and calcitriol for hypoparathyroidism, and glucocorticoid plus mineralocorticoid replacement for adrenal insufficiency, with structured lifelong screening for additional autoimmune endocrinopathies as they emerge.

Primary adrenal insufficiency (Addison disease) is destruction or dysfunction of the adrenal cortex, most often autoimmune, causing combined cortisol and aldosterone deficiency with hyperpigmentation, hyponatremia, and hyperkalemia. Lifelong glucocorticoid replacement with hydrocortisone plus mineralocorticoid replacement with fludrocortisone is required, with sick-day dose increases to prevent adrenal crisis.

Genitourinary syndrome of menopause is the chronic, progressive constellation of vulvovaginal and lower urinary tract symptoms caused by estrogen deficiency, presenting with vaginal dryness, dyspareunia, and recurrent urinary symptoms in menopausal women. It is a clinical diagnosis treated first with nonhormonal moisturizers and lubricants, then low-dose vaginal estrogen, with ospemifene or vaginal prasterone reserved as second-line options.