Menopause is the age at which female reproduction ceases. During the time leading up to the full menopause, or the climacteric, periods become increasingly sparse and irregular. Levels of estrogen and progesterone fall while those of LH and FSH increase. After the menopause, known effects in women include a rise in cardiovascular events such as heart attack as well as osteoporosis, hot flashes and mood swings.
The age at which menopause is reached in an individual women is often difficult to predict but is largely based upon the numbers of ovarian follicles that a women possesses at birth. Reports suggest that a baby girl has a million ovarian follicles at birth and rapidly loses them during puberty and early adulthood. An average women will use 400-500 ovarian follicles during her reproductive lifetime and menopause occurs when this supply is depleted. Reviews of the files of DES exposed women suggested that DES seemed to cause early menopause but this was difficult to show conclusively.
Hatch and other authors who have spent large amounts of their careers studying the adverse effects of DES (diethylstilbestrol) recently prospectively examined the possible correlation of DES exposure in utero with early menopause (27). These authors initially reviewed animal data suggesting that there was a correlation between intrauterine DES exposure and reduced numbers of ova leading to early menopause. The authors contacted four large cohorts of DES exposed women inquiring specifically about reproductive history and the occurrence of menopause. Compared with unexposed women, DES-exposed women were approximately 50% more likely to have reached natural menopause at each age. The average age at menopause in the DES cohort was 51.5 years and 52.2 for unexposed women.
The effect of diethylstilbestrol increased with cumulative doses and was double with cumulative DES doses of more than 10 grams. The authors suggest that DES in utero reduced the ovarian follicle pool, led to more rapid follicle depletion or led to changes in hormone synthesis and metabolism in these DES daughters. Followup of this study is certain in the future since only half of the 4,210 had experienced menopause at the time of the study.
27. Hatch E.E. et al. Age at natural Menopause in Women Exposed to Diethylstilbestrol in Utero. Am. J. Epidemiol. 164:682-688, 2006.