History or Findings Suggesting Causes of Amenorrhea

Body habitus

Overweight or obesity*

Hirsutism

Acne

Polycystic ovary syndrome

Underweight

Insufficient calorie intake or utilization (eg, excessive dieting, food insecurity, malabsorption)

Excessive calorie expenditure (eg, strenuous exercise, hypermetabolic disorders)

Physical or emotional stress

Chronic disease

Functional hypothalamic amenorrhea

Insufficient caloric intake combined with hypothermia, cardiac arrhythmias, hypotension, electrolyte abnormalities (eg, hypokalemia, hypomagnesemia)

Functional hypothalamic amenorrhea due to anorexia nervosa or starvation

Reduced gag reflex, palatal lesions, subconjunctival hemorrhages

Functional hypothalamic amenorrhea due to bulimia with frequent vomiting

Short stature

Primary amenorrhea, webbed neck, widely spaced nipples

Turner syndrome

Skin or hair findings

Hirsutism or virilization

Acne

Androgen excess due to

• Polycystic ovary syndrome

• An androgen-secreting tumor

• Cushing syndrome

• Adrenal hyperandrogenism

• Medications (eg, androgens, antidepressants, danazol, high-dose progestins)Medications (eg, androgens, antidepressants, danazol, high-dose progestins)

Enlarged ovaries

Androgen excess due to

• Polycystic ovary syndrome

• An androgen-secreting ovarian tumor

• 17-Hydroxylase deficiency

Primary amenorrhea

Androgen excess due to

• Ovotesticular difference of sexual development

• Pseudohermaphroditism

• An androgen-secreting tumor

• Adrenal hyperandrogenism

• Gonadal dysgenesis

Striae

Moon facies, buffalo hump, truncal obesity, thin extremities, virilization, hypertension

Cushing syndrome

Acanthosis nigricans

Obesity, hirsutism, acne

Polycystic ovary syndrome

Vitiligo or hyperpigmentation of the palm

Orthostatic hypotension

Addison disease

Constitutional symptoms

Hot flashes

Vaginal dryness

Risk factors such as chemotherapy, pelvic irradiation, or an autoimmune disorder

Primary ovarian insufficiency

Pituitary tumors

Weight loss, heat intolerance

Anxiety, insomnia

Warm, moist skin

Tachycardia, tremor

Hyperthyroidism

Weight gain, cold intolerance

Constipation, hypersomnia

Coarse, thick skin, loss of eyebrow hair

Bradycardia, delayed deep tendon reflexes

Hypothyroidism

Cyclic pelvic pain and primary amenorrhea

Normal breast development and secondary sexual characteristics

Bulging vagina (due to hematocolpos)

Hematometra

Genital outflow obstruction

Breast symptoms or findings

Galactorrhea

—

Hyperprolactinemia

Headache, visual field defects

Hyperprolactinemia caused by a pituitary tumor

Absence or incomplete breast development (and of secondary sexual characteristics)

Normal adrenarche

Constitutional delay of puberty

Hypogonadotropic hypogonadism

Primary ovarian insufficiency

Nonclassic congenital adrenal hyperplasia 

Absence of adrenarche

Hypothalamic-pituitary dysfunction

Absence of adrenarche with impaired sense of smell

Kallmann syndrome

Reproductive tract abnormalities

Ambiguous genitals

Virilization

Difference of sexual development

Clitoral enlargement

At birth

Virilization

Congenital adrenal hyperandrogenism

Difference of sexual development

Vaginal agenesis

Primary amenorrhea

Absence of cervix and uterus

Sometimes uterine enlargement (due to hematometra)

Pelvic kidney or other urinary tract anomalies

Mullerian agenesis

Ovarian enlargement (bilateral)

Symptoms of estrogen deficiency

Primary ovarian insufficiency due to autoimmune oophoritis

Hirsutism or virilization

Polycystic ovary syndrome

17-Hydroxylase deficiency

Medications or substance use

Medications and substances that can cause hyperprolactinemia (with symptoms including galactorrhea, menstrual irregularities, or loss of libido); the mechanism for many of these is blocking dopamine receptors in the pituitary gland†:

• Estrogens

• Antihypertensives (eg, methyldopa, reserpine, verapamil)Antihypertensives (eg, methyldopa, reserpine, verapamil)

• Gastrointestinal medications (eg, cimetidine, metoclopramide, domperidone)Gastrointestinal medications (eg, cimetidine, metoclopramide, domperidone)

• Antidepressants, tricyclics (eg, impiramine), monoamine oxide inhibitors, and some selective serotonin reuptake inhibitors

• Antipsychotics, 2nd generation (eg, molindone, olanzapine, risperidone, haloperidol) Antipsychotics, 2nd generation (eg, molindone, olanzapine, risperidone, haloperidol)

• Antipsychotics, conventional (eg, haloperidol, phenothiazines, pimozide)Antipsychotics, conventional (eg, haloperidol, phenothiazines, pimozide)

• CocaineCocaine

• Opioids

Galactorrhea

Drug-induced hyperprolactinemia

Medications that increase androgen levels:

• Androgens (eg, testosterone, dehydroepiandrosterone)Androgens (eg, testosterone, dehydroepiandrosterone)

• High-dose androgenic progestins (eg, levonorgestrel, norethisterone acetate)High-dose androgenic progestins (eg, levonorgestrel, norethisterone acetate)

• DanazolDanazol

• Anabolic steroids

• Antiseizure drugs (eg, carbamazepine, phenytoin, valproate)Antiseizure drugs (eg, carbamazepine, phenytoin, valproate)

Hirsutism or virilization

Androgen excess