Weight loss can cause elevations in the hormone ghrelin which inhibits the hypothalamic-pituitary-ovarial axis. Elevated concentrations of ghrelin alter the amplitude of GnRH pulses, which causes diminished pituitary release of LH and follicle-stimulating hormone (FSH). Low levels of the hormone leptin are also seen in females with low body weight. Like ghrelin, leptin signals energy balance and fat stores to the reproductive axis. Decreased levels of leptin are closely related to low levels of body fat, and correlate with a slowing of GnRH pulsing. Drug-induced
Certain medications, particularly contraceptive medications, can induce amenorrhoea in a healthy woman. The lack of menstruation usually begins shortly after beginning the medication and can take up to a year to resume after stopping its use. Hormonal contraceptives that contain only progestogen, like the oral contraceptive Micronor, and especially higher-dose formulations, such as the injectable Depo-Provera, commonly induce this side effect. Extended cycle use of combined hormonal contraceptives also allow suppression of menstruation. Patients who stop using combined oral contraceptive pills (COCP) may experience secondary amenorrhoea as a withdrawal symptom. The link is not well understood, as studies have found no difference in hormone levels between women who develop amenorrhoea as a withdrawal symptom following the cessation of COCP use and women who experience secondary amenorrhoea because of other reasons. New contraceptive pills which do not have the normal seven days of placebo pills in each cycle, have been shown to increase rates of amenorrhoea in women.
If LH and FSH are elevated, menopause or primary ovarian insufficiency should be considered. Normal or low levels of FSH and LH prompts further evaluation with patient history and the physical exam. Testosterone, DHEA-S, and 17-hydroxyprogesterone levels should be obtained if there is evidence of excess androgens, such as hirsutism or acne. 17-hydroxyprogesterone is elevated in congenital adrenal hyperplasia. Elevated testosterone and amenorrhea can suggest PCOS. Elevated androgens can also be present in ovarian or adrenal tumors, so additional imaging may also be needed. History of disordered eating or excessive exercise should raise concern for hypothalamic amenorrhea. Headache, vomiting, and vision changes can be signs of a tumor and needs evaluation with MRI. Finally, a history of gynecologic procedures should lead to evaluation of Asherman syndrome with a hysteroscopy or progesterone withdrawal bleeding test. Treatment
Treatment for amenorrhea varies based on the underlying condition. Treatment not only focuses on restoring menstruation, if possible, but also preventing additional complications associated with the underlying cause of amenorrhea. Primary amenorrhea
In primary amenorrhea, the goal is to continue pubertal development, if possible. For example, most patients with Turner syndrome will be infertile due to gonadal dysgenesis. However, patients are frequently prescribed growth hormone therapy and estrogen supplementation to achieve taller stature and prevent osteoporosis. In other cases, such as MRKH, hormones do not need to be prescribed since the ovaries are able to function normally.