Sequential classification of endocrine stages during reproductive aging in women: the FREEDOM study.

OBJECTIVE: Reproductive aging involves complex endocrine changes affecting women's fertility, health, and well-being; however, understanding of the specific changes involved is limited by the lack of detailed quantitative studies. We undertook a thorough study with the aim of characterizing the different endocrine stages involved in female reproductive aging. DESIGN: FREEDOM is a cohort study designed to determine the endocrine changes during reproductive aging in women. Here, we ascertained the different endocrine patterns in a representative population and developed a staging system. In this study, 112 women aged 30 to 58 years collected daily urine samples over a 6- to 18-month period and recorded their menstrual periods. A total of 36,786 samples were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone, estrone 3-glucuronide, and pregnanediol 3-glucuronide. RESULTS: A classification of five sequential endocrine stages of reproductive aging was developed: stage 1, regular menstrual cycles with mean initial (day 1-5) FSH less than 5 IU/L; stage 2, regular cycles with FSH greater than 5 IU/L; stage 3, menstrual irregularity (with the appearance of "delayed-response cycles"); stage 4, acyclical ovarian activity with no evidence of ovulation and luteinization; and stage 5, ovarian quiescence and persistently raised gonadotropins. Distinct hormonal characteristics during the follicular and luteal phase were noted at each stage. CONCLUSION: This classification provides a detailed insight into the endocrinology of reproductive aging in women that could be useful for both clinical guidance and personal health care.

Comparison between creatinine and pregnanediol adjustments in the retrospective analysis of urinary hormone profiles during the human menstrual cycle.

Measurement of reproductive hormones in urine is a practical way of obtaining large amounts of information; however, there is still controversy on how to overcome problems derived from volume fluctuations between samples. Creatinine adjustment is a widely accepted solution, however, it introduces an extra cost, and large studies involving multiple sequential determinations would benefit from more economical solutions. We determined the value of creatinine adjustment, and compared it with a mathematical method that uses the smoothed profile of pregnanediol (PdG) as a reference to adjust other hormonal markers. To do this, we investigated the effects on three major urinary reproductive hormonal markers (luteinizing hormone (LH), estrone 3-glucuronide (E1G) and PdG) in 17 complete menstrual cycles. Detection of the day of LH peak did not differ between raw and adjusted data. Creatinine adjustment reduced variation in pre-ovulatory E1G levels between individuals, though the effect was negligible within individuals. No significant differences were found regarding post-ovulatory PdG rise. Although creatinine adjustment significantly reduces variability, producing smoother profiles, an equivalent degree of smoothness is obtained using the PdG adjustment. We conclude that under the current technology, for the retrospective study of urinary hormonal profiles in the human menstrual cycle, PdG adjustment is a valid alternative to creatinine.