The natural process in which the older the female fetus, girl or woman gets the fewer are the eggs (as primordial follicles) left in the ovaries; the huge majority of eggs are lost because of atresia, only a tiny fraction by ovulation. Before the eggs are depleted there is a mild or moderate elevation in serum FSH when measured during the menstrual phase (often called a day 3 FSH. When the eggs are more or less depleted there will be primary ovarian failure and, in women who have had periods, the menopause will take place, perhaps prematurely (premature menopause). Infertility, however, usually precedes total egg depletion by up to 10 years. See also mitochondrion and oopause.

Early experience with superovulation for in vitro fertilisation, particularly at the original US program in Norfolk VA, saw women patients classified into three classes of responders, depending on how many eggs were obtained at egg retrieval. Poorer than usual outcomes could occur with either a low response or a high response (the high responders generally have polycystic ovaries, with a risk of ovarian hyperstimulation syndrome (OHSS). Many maneuvers have been used to try and retrieve more eggs among low responders, such as starting high dose FSH on day 1, the adding of growth hormone, the avoidance of GnRH-agonists etc., all generally without improving the results. Day 3 serum FSH levels can be high in low responders, indicating a depletion of eggs in the ovaries.

The last natural menstrual period (so often a retrospective diagnosis); hence the adjective menopausal, the natural state a woman is in after the ovaries have stopped ovulating because of depletion of eggs. The normal age of menopause is between 40 and 55 years, with an average in Western societies of 50-51 years.

Failure of the ovaries to produce enough follicles, because of a problem in the ovary itself, and resulting in depletion of eggs before the age of 40 years (known as premature menopause, a cause of secondary amenorrhea), or maybe even before the age puberty is expected (causing failure of puberty to happen, including primary amenorrhea). Sometimes occurs in spite of good numbers of primordial follicles that (inexplicably, so far) won't develop. The younger the woman, the more likely that an aneuploidy will be found if a karyotype is done on blood or on a biopsy of the ovary. Estrogen replacement therapy is important to prevent general jeopardy to health, including prevention of osteoporosis.

Measurement of follicle stimulating hormone in serum. Useful at the time of menstruation for indicating a significantly decreased number of eggs in the ovaries in the few years leading up to menopause (that is, indicative of depletion of eggs or primary ovarian failure); Continuously high in women after menopause, and then excreted in high amounts in the urine (from which, in turn human menopausal gonadotropin is derived).

In women, when measured during menstruation, inversely related to the serum FSH (and probably provides no more information than the day 3 FSH level in predicting depletion of eggs); in men with azoospermia, levels predict the likelihood of being able to obtain sperm for ICSI at testicular sperm extraction.