URINARY FOLLICLE-STIMULATING-HORMONE AS A BIOLOGICAL MARKER OF OVARIAN TOXICITY

Reproductive senescence in women is thought to be triggered, by a diminishing reserve of oocytes. Therefore, toxic effects to the ovary (i.e., oocyte destruction) may be manifest as an earlier menopause. One example of a reproductive toxin that may act this way is cigarette smoke. Constituents of cigarette smoke have been shown to destroy oocytes in rodents (1); it is well known that cigarette smokers enter the menopause earlier than nonsmokers. In addition, an agent that causes oocyte destruction may not cause any appreciable reproductive effects until the climacteric (unlike cigarette smoke). A promising biologic marker of ovarian reserve that may permit a more precise and earlier assessment of reproductive senescence is the concentration of FSH during the follicular phase of the menstrual cycle. Serum FSH increases with age and with surgical removal of ovarian tissue. At menopause the diminishing supply of oocytes and resulting reduction in ovarian hormones (particularly inhibin) releases the hypothalamic-pituitary axis from ovarian control. This results in the high levels of FSH found in postmenopausal women. Higher FSH levels indicate fewer functioning oocytes. These endocrine changes occur gradually over many years and may precede any marked change in menstrual cycle regularity or ovulation. Serum FSH has been evaluated as a predictor of success for IVF programs. In one study of 441 women, those with elevated FSH levels had fewer oocytes retrieved and a lower pregnancy rate (2). Although the number of pregnancies to women with elevated FSH levels was small, these pregnancies were twice as likely to end in spontaneous abortions than pregnancies to women without elevated FSH levels. This finding may indicate that the quality as well as the quantity of remaining oocytes influence serum FSH levels. In another study of 1,300 cycles in which oocytes were retrieved, basal serum FSH was a better predictor of successful IVF than was chronological age (3). These data are based on FSH in serum. However, FSH in serum is not a marker that can easily be used for epidemiologic purposes. For a biologic marker to be useful for epidemiologic studies, it should be obtainable by noninvasive means and readily provided by nonclinical populations. Urinary specimens would be appropriate for this purpose. To evaluate the hypothesis that urinary FSH is closely correlated with serum FSH, we collected serum and urine samples from 50 women on the 3rd day of their menstrual cycle.