Monitoring the Menstrual Cycle of Humans and Lowland Gorillas Based on Urinary Profiles of Bioactive Follicle-Stimulating Hormone and Steroid Metabolites*

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Abstract
A sensitive and specific in vitro granulosa cell aromatase bioassay was adapted to measure bioactive FSH (bio-FSH) levels in urine samples. Urinary levels of bio-FSH, immunoreactive LH, estrone conjugates, and pregnanediol-3-glucuronide (PdG) were measured in first morning urine samples during the menstrual cycle in six cycling women and four lowland gorillas. The cycle length of women was relatively constant [28 ± 1 (±SD) days], but varied from 28–38 days for lowland gorillas; the length of the luteal phases was relatively constant for both. All subjects had a midcycle LH peak and a luteal phase elevation in PdG. In addition, urinary estrogen excretion displayed a midcycle elevation that preceded the LH peak and a luteal phase increase similar to that of PdG. The bio-FSH levels in urine of cycling women, although at almost 100-fold higher concentrations, exhibited a pattern that closely resembled that of serum bio-FSH levels reported earlier, with an early follicular phase rise and a midcycle peak. Statistical analysis indicated a highly significant correlation (r = 0.90) between serum and urinary bio-FSH levels during the human menstrual cycle and in women in several hypo- and hypergonadotropic states, including oral contraceptive pill users, hypothalamic amenorrhea, premature ovarian failure, and postmenopause. Although a midcycle bio-FSH surge was also detected in lowland gorillas, two peaks of bio-FSH levels were consistently found during the follicular phase. The late follicular phase increase in bio-FSH levels was presumably involved in follicle selection and preceded the midcycle FSH peak by about 6 days, whereas the timing of the early follicular phase peak was variable, suggesting the involvement of complex regulatory mechanisms. These findings suggest that measurement of urinary bio-FSH levels in humans reflects serum bio-FSH in subjects in several physiological and pathological states. Studies of urinary bio-FSH levels in humans and nonhuman primates are useful in monitoring menstrual cycles, and the gorillas may be a model for understanding human reproductive cycles. The urinary granulosa cell aromatase bioassay should be useful for future assessment of bio-FSH levels in situations where serum measurements are impractical or in animal species for which specific FSH RIAs are not available.

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