Secondary amenorrhea implies ending of menstruation after menstruation has already begun. A list of etiologies of secondary amenorrhea is presented in the box, grouped according to evidence of ovarian function (from tests discussed in the section on primary amenorrhea). If menstruation definitely takes place, especially if it continues for several months or years, this eliminates some of the etiologies of primary amenorrhea such as m;auullerian dysgenesis and most types of male pseudohermaphroditism. Otherwise, the list of possible causes and the workup are similar to that for primary amenorrhea. Even chromosome studies are still useful; in this case, to rule out Turner’s syndrome or its variants. Certain conditions are much more important or frequent in secondary, as opposed to primary, amenorrhea; these include hyperprolactinemia (with or without galactorrhea), early menopause, psychogenic cause, anorexia nervosa, severe chronic illness, and hypothyroidism. Normal pregnancy should also be excluded.
Hyperprolactinemia is found in 20%-30% of patients with secondary amenorrhea. There may or may not be galactorrhea. The condition may be idiopathic, may be due to pituitary tumor, or sometimes develops when a person taking oral contraceptives stops the medication or in the postpartum period.
Some cases of periodic amenorrhea or varying time periods without menstruation are due to anovulation. Anovulation is said to cause up to 40% of all female infertility. Some of these patients have enough estrogen production to permit the endometrium to reach the secretory phase, so these women will respond to a dose of progesterone (“progesterone challenge”) by menstruating. These women frequently will ovulate if treated with clomiphene, which has an antiestrogen action on the hypothalamus. Other patients will not respond to progesterone challenge and usually do not respond to clomiphene. Some of these women have hypothalamic function deficiency, pituitary failure, exercise-induced (e.g., rigorous athletic training) or stress-related amenorrhea, anorexia nervosa, or ovarian failure.

Some Etiologies of Secondary Amenorrhea Classified According to Ovarian Function
I. Pregnancy
II. Decreased ovarian hormone production
A. Primary ovarian failure
1. Normal menopause
2. Some cases of gonadal dysgenesis (Turner’s syndrome)
3. Acquired ovarian failure (idiopathic, postradiation, postchemotherapy, postmumps infection)
4. PCO disease
B. Secondary ovarian failure
1. High pituitary prolactin value (with or without galactorrhea)
2. Hypothalamic failure to secrete adequate GTRH levels (tumor, trauma, infection, nonintracranial illness)
3. Pituitary failure (primary pituitary tumor, Sheehan’s syndrome, empty sella syndrome)
4. Anorexia nervosa or severe malnutrition
5. Rigorous athletic training
6. Psychogenic amenorrhea
7. Severe acute or chronic illness
8. Increased nonovarian estrogen levels (tumor, obesity, therapy)
9. Hypothyroidism or hyperthyroidism
10. Cushing’s disease or Addison’s disease
11. Poorly controlled diabetes
III. Increased ovarian estrogen or androgen production
A. Androgen-secreting ovarian tumor
B. Estrogen-secreting ovarian tumor
IV. Normal ovarian hormone production
A. Local uterine pathology