Amenorrhea pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Hypogonadotropic amenorrhoea refers to conditions where there are very low levels of serum FSH and LH. Generally, inadequate levels of these hormones lead to inadequately stimulated ovaries who then fail to produce enough estrogen to stimulate the endometrium (uterine lining), hence amenorrhoea. This is typical for conditions of pubertal delay, hypothalamic or pituitary dysfunction. In general, women with hypogonadotropic amenorrhoea are potentially fertile.
Hypergonadotropic amenorrhoea refers to conditions with high levels of FSH (and LH). FSH levels are typically in the menopausal range. This implies that the ovary or gonad does not respond to pituitary stimulation. Gonadal dysgenesis or premature menopause are possible causes. Chromosome testing is usually indicated in younger individuals with hypergonadotropic amenorrhoea.
In normogonadotropic amenorrhoea, FSH levels are in the normal range. This would suggest that the hypothalamic-pituitary-ovarian axis is functional. Amenorrhoea may be due to outflow obstruction, or abnormal ovarian regulation or excess androgens as seen in polycystic ovary syndrome.
Cushing's Disease/Syndrome can also cause amenorrhoea due to excessive amounts of cortisol in the blood stream.
Primary amenorrhea
In primary amenorrhea there is absence of menarche by the age of 16. Menstruation cycles never begin. There will be a delay of menses one year beyond the family history of first menses.
There is no defining sexual characteristics by age 14. Primary amenorrhea may be caused by developmental problems such as the congenital absence of the uterus, or failure of the ovary to receive or maintain egg cells. Also, delay in pubertal development will lead to primary amenorrhoea.
Secondary amenorrhea
Secondary amenorrhea is defined as absence of menses in a woman who had previously menstruated for at least 3 cycles or 6 months. Secondary amenorrhea is more common than primary amenorrhea.
Secondary amenorrhea is often caused by hormonal disturbances from the hypothalamus and the pituitary gland or from premature menopause, or intrauterine scar formation.
Specific types of amenorrhoea
Exercise amenorrhoea
Female athletes or women who perform considerable amounts of exercise on a regular basis are at risk of developing 'athletic' amenorrhoea. It was thought for many years that low body fat levels and exercise related chemicals (such as beta endorphins and catecholamines) disrupt the interplay of the sex hormones estrogen and progesterone. However recent studies have shown that there are no differences in the body composition, or hormonal levels in amenorrheic athletes. Instead, amenorrhea has been shown to be directly attributable to a low energy availability. Many women who exercise at a high level do not take in enough calories to expend on their exercise as well as to maintain their normal menstrual cycles. [2]
A second serious risk factor of amenorrhea is severe bone loss sometimes resulting in osteoporosis and osteopenia. It is the third component of an increasingly common disease known as female athlete triad syndrome. The other two components of this syndrome are osteoporosis and disordered eating. Awareness and intervention can usually prevent this occurrence in most female athletes.
Drug-induced amenorrhea
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 a medication. Hormonal contraceptives that contain only progestogen like the oral contraceptive Micronor, and especially higher-dose formulations like the injectable Depo Provera commonly induce this side-effect. Recently, an extended cycle combined oral contraceptive pill which aims to purposefully induce amenorrhea (Lybrel), has been approved by the FDA.