Evaluation of secondary amenorrhea
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).
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
A stepwise hormonal workup, not a single test: secondary amenorrhea is absence of menses for 3 months with prior regular cycles or 6 months with prior irregular cycles; the cause is found by working…
- Epidemiology
Pregnancy is the leading cause in reproductive-age women: it is the reason beta-hCG is the mandatory first test in every patient, regardless of contraceptive history.
- Risk factors
Low body weight and high energy expenditure: severe weight loss, eating disorders, and competitive athletics suppress hypothalamic GnRH pulsatility.
- Pathophysiology
Normal menstruation requires an intact axis at four levels: cyclic hypothalamic GnRH release, pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, an ovary that…
- Clinical features
Absence of menses meeting the time-based definition: no menses for 3 months with prior regular cycles, or 6 months with prior irregular cycles.
- Differential diagnosis
Pregnancy: most common cause overall; excluded by a positive beta-hCG before any further workup.
- Diagnosis
The diagnosis is established by a fixed, sequential hormonal and challenge-test algorithm, not a single confirmatory test: the pattern of results at each step localizes the cause to the outflow…
- Management
Treat the identified cause; do not give empiric estrogen or progestin before the workup is complete: starting hormones before establishing the cause risks masking a pituitary tumor or missing pregnancy.
- Complications
Endometrial hyperplasia and cancer: chronic unopposed estrogen from PCOS-type anovulation confers a 4- to 8-fold increased risk of endometrial cancer without cyclic progestin.
- Prognosis
Excellent when the cause is reversible: hypothyroidism, medication-induced hyperprolactinemia, and functional hypothalamic amenorrhea typically resume normal menses once the trigger is corrected.
- Prevention
Maintain adequate energy availability in athletes and dieters: counsel against severe caloric restriction and excessive training load, since prolonged energy deficit is a preventable cause of hypothalamic amenorrhea.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Hypothalamic amenorrhea
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.
- Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder of chronic anovulation and is the most common cause of hirsutism and anovulatory infertility in women. First-line treatment is weight loss for patients with an elevated BMI, combined oral contraceptives for menstrual dysfunction and hirsutism when fertility is not desired, and clomiphene citrate or letrozole for ovulation induction when fertility is desired.
- Primary ovarian insufficiency
Primary ovarian insufficiency is loss of ovarian follicular function before age 40, defined by amenorrhea with a low estradiol and an elevated FSH on two occasions a month apart. It carries fertility, bone, and cardiovascular consequences that estrogen replacement, continued until the normal age of menopause, is meant to prevent.
- Sheehan syndrome
Sheehan syndrome is postpartum pituitary infarction after massive obstetric hemorrhage, causing panhypopituitarism with failure of lactation and deficiencies of glucocorticoids, thyroid hormone, and sex hormones. First-line treatment is glucocorticoid replacement started before thyroid hormone, followed by levothyroxine and, when indicated, sex hormone and growth hormone replacement.
- Turner syndrome
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.
- Evaluation of primary amenorrhea
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.