Women’s Health


Our study was comprised of a cohort of women enrolled in the Tremin Trust, who had been providing detailed prospective reports of menstrual and reproductive histories, and information on life-cycle events and health status for up to 30 years. From 150 of these women, we collected daily first-morning urine specimens during a 6-month window during each of the five project years. The specimens were assayed for the principal steroids and gonadotropins involved in regulating ovarian cycles and in signaling reproductive aging. Statistical models linked the women’s menstrual, reproductive, and health related histories to the experience of the transition, modeled the effects of hormonal patterns on menstrual bleeding during the perimenopause, and related features of the transition to the underlying process of follicular depletion.

This work differed from other studies of the menopause in several important respects. First we had access to decades worth of prospectively-reported data. Second, unlike most other studies of the endocrinology of the menopause, we worked with a population-based cohort of women who were all recruited well before the transition. Thus, they were not selected for any aspect of their experience of the transition. Third, we propose to develop and apply new mathematical models that allow us to link characteristics of the menopausal transition to prior history and underlying biological mechanisms. The work complements, but does not reproduce, the current NIA initiative.

The project gives new insight into the patterns and causes of variation in a women’s experience of the menopausal transition, yields a better understanding of how individual-level experience gives rise to population-level patterns of reproductive aging, enriches clinical practice by providing information on how past menstrual patterns are linked to experience throughout the menopausal transition, and provides a foundation for future epidemiological studies of the health consequences of patterns of reproductive aging. The data set produced in conjunction with this research will provide a rich resource for future investigators.

A public use data set and full documentation for the hormone study are available from the ICPSR.


  • Brindle E, Miller RC, Shofer JB, Klein NA, Soules MR, O’Connor KA. (2006) Urinary beta-luteinizing hormone and beta-follicle stimulating hormone immunoenzymometric assays for population research. Clinical Biochemistry 39(11):1071-79.
  • Ferrell RJ, O’Connor KA, Rodriguez G, Gorrindo T, Holman DJ, Brindle E, Miller RC, Schechter DE, Korshalla L, Simon J, Mansfield PK, Wood JW, Weinstein M. (2005) Monitoring reproductive aging in a five year prospective study: aggregate and individual changes in steroid hormones and menstrual cycle lengths with age. Menopause 12(5):567-577.
  • Ferrell RJ, O’Connor KA, Rodriguez G, Holman DJ, Brindle E, Miller RC, Simon J, Mansfield PK, Wood JW, Weinstein M. (2007) Monitoring reproductive aging in a 5-year prospective study: aggregate and individual changes in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with age. Menopause 14(1):29-37.
  • Ferrell RJ, Simon JA, Pincus SM, Holman DJ, O’Connor KA, Rodriguez G, Weinstein M. (2006) The length of perimenopausal menstrual cycles increases later and to a greater degree than previously reported. Fertility and Sterility 86(3):619-24.
  • Gorrindo T, Lu Y, Riley A, Singer B, Pincus S, Simon JA, Weinstein M (2007) Lifelong Menstrual Histories are Typically Erratic and Trending – A Taxonomy. Menopause14(1):74-88
  • Haaga J, O’Connor KA, Weinstein M, Wise, P (2010) Introduction. Reproductive Aging. Annals of the New York Academy of Sciences, (1204):1-10
  • Holman DJ, Grimes MA, Achterberg JT, Brindle E, O’Connor KA. (2006) The distribution of postpartum amenorrhea in rural Bangladeshi women. The American Journal of Physical Anthropology 129(4):609-19.
  • Holman DJ, Grimes MA, Brindle E, O’Connor KA. (2004) Hormonal correlates for the initiation of breastfeeding in Bangladeshi women. Hormones and Behavior 46(4):382-391.
  • Holman DJ, O’Connor KA and Wood JW (2006) Age and Female Reproductive Function: Identifying the Most Important Determinants. In Sauvain-Dudgeril C, Leridon H, Mascie-Taylor N, (eds): Human Clocks: The Bio-Cultural Meanings of Age. Oxford University Press, Oxford.
  • Holman DJ, Rasheed FN, Stroud CM, Brindle E, O’Connor KA, Campbell KL (1998) A commercial pregnancy test modified for field studies of fetal loss. Clinica Chimica Acta. 271(1):25-44.
  • Holman DJ, Wood JW (2001) Pregnancy loss and fecundability in women. In Ellison PT (ed.) Reproductive Ecology and Human Evolution. Hawthorne, NY: Aldine de Gruyter. pp. 15-38.
  • Holman DJ, Wood JW, Campbell KL (2000) Age-dependent decline of female fecundity is caused by early fetal loss. Chapter 9 in te Velde ER, Broekmans F, and Pearson P (eds.) Female Reproductive Ageing. Studies in Profertility series, Vol 9, Carnforth, UK: Parthenon Publishing Group. pp. 123-136.
  • McConnell HJ, O’Connor KA, Brindle E, Williams NI (2002) Validity of methods for analyzing urinary steroid data to detect ovulation in athletes. Medicine and Science in Sports and Exercise 34(11):1836-1844.
  • Miller RC, Brindle E, Holman DJ, Shofer JB, Klein NA, Soules MR, O’Connor KA (2004) Comparison of specific gravity and creatinine methods for normalizing urinary reproductive hormone concentrations. Clinical Chemistry 50(5):924-32.
  • Mitchell ES, O’Connor KA, Taylor HJ, Brindle E, Smith-DiJulio K, Mariella A, Tao EY, Woods NF. (under revision) Urinary FSH and Estrone Patterns During the Menopausal Transition: From the Seattle Midlife Women’s Health Study. Climacteric.
  • O’Connor KA, Brindle E, Holman DJ, Klein NA, Soules MR, Campbell KL, Kohen F, Munro CJ, Shofer J, Lasley WL, Wood JW. (2003) Urinary estrone conjugate and pregnanediol-3-glucuronide enzyme-immunoassays for population research. Clinical Chemistry 49(7):1139-1148.
  • O’Connor KA, Brindle E, Miller RC, Shofer JB, Ferrell RJ, Klein NA, Soules MR, Holman DJ, Mansfield PK, Wood JW, Weinstein. (2006) Ovulation detection methods for urinary hormones: Precision, daily and intermittent sampling, and a combined hierarchical method, Human Reproduction 21(6):1442-1452.
  • O’Connor KA, Brindle E, Shofer JB, Miller RC, Klein NA, Soules MR, Campbell KL, Mar C, Handcock MS. (2004) Statistical correction for non-parallelism in a urinary enzyme immunoassay. Journal of Immunoassay and Immunochemistry 25(3):259-278.
  • O’Connor KA, Holman DJ, Wood JW (1998). Declining fecundity and ovarian ageing in natural fertility populations. Maturitas 30:127-136.
  • O’Connor KA, Holman DJ, Wood JW (2001) Menstrual cycle variability and the perimenopause. American Journal of Human Biology 13(4):465-478.
  • Riley AP, Weinstein M, Ridley JC, Mormino J, and Gorrindo T (2001). Menarcheal Age and Subsequent Patterns of Family Formation. Social Biology 48(1-2):21-43.
  • Weinstein M, Gorrindo T, Riley A, Mormino J, Niedfeldt J, Singer B, Rodriguez G, Simon J, and Pincus S (2003). Timing of Menopause and Patterns of Menstrual Bleeding. Am. J. Epid. 158(8):782-791.
  • Weinstein M, O’Connor KA, ed. (2010) Reproductive Aging.:Annals of the New York Academy of Sciences (Volume 1204).
  • Wood JW, Holman DJ, O’Connor KA (2001) Did menopause evolve by antagonistic pleiotropy? In M. Schultz (ed.), Homo-unsere Herkunft und Zukunft. Gottingen: Cuvillier Verlag. pp. 483-90.

(last updated: 4 August, 2020)