Longitudinal changes in hypothalamic and ovarian function in perimenopausal women with anovulatory cycles: relationship with vasomotor symptoms


      To determine whether the transition to menopausal status is unidirectional and predictable with aging.


      Longitudinal evaluation of the menstrual cycle hormone patterns and experience of vasomotor symptoms in an anovulatory, perimenopausal cohort, during cycles that occurred 1 and 2 years after an anovulatory cycle.


      Academic center.


      One hundred fifty-nine of 840 women in the Daily Hormone Study, a substudy of the Study of Women's Health across the Nation (SWAN), had anovulatory cycles. Their menstrual cycle patterns were previously described. This report describes their cycle patterns and vasomotor symptoms in the subsequent 2 years.



      Main Outcome Measure(s)

      Daily urinary hormone levels of FSH, LH, and estrogen and P metabolites and reports of daily occurrence of vasomotor symptoms.


      While a tendency to develop cycles having a loss of negative feedback of estrogen on LH secretion was seen before menopause, there is no clear progression of cycle patterns in anovulatory women. Anovulation did not predict menopause within 2 years. Vasomotor symptoms occur before menopause, as experienced by 73% of the women. Vasomotor symptoms were not related to cycle pattern.


      Any cycle pattern may be related to vasomotor symptoms. The best predictor of vasomotor symptoms is a prior history of vasomotor symptoms.

      Key Words

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      1. World Health Organization. Research on the menopause in the 1990s: report of a WHO scientific group. World Health Organization Technical Report Series No. 866, 1996.

        • Vande Wiele R.L.
        • Bogumil J.
        • Dyrenfurth I.
        • Ferin M.
        • Jewelewicz R.
        • Warren M.
        • et al.
        Mechanisms regulating the menstrual cycle in women.
        Recent Prog Horm Res. 1970; 26: 63-103
        • Weiss G.
        • Skurnick J.H.
        • Goldsmith L.T.
        • Santoro N.F.
        • Park S.J.
        Menopause and hypothalamic-pituitary sensitivity to estrogen.
        JAMA. 2004; 292: 2991-2996
        • Sowers M.F.
        • Crawford S.L.
        • Sternfeld B.
        • Morganstein D.
        • Gold E.
        • Greendale G.
        • et al.
        Design, survey, sampling and recruitment methods of SWAN: a multi-center, multi-ethnic, community-based cohort study of women and the menopausal transition.
        in: Lobo R.A. Kelsey J. Marcus R. Menopause: Biology and pathobiology. Academic Press, San Diego2000: 175-188
        • Santoro N.
        • Lasley B.
        • McConnell D.
        • Allsworth J.
        • Crawford S.
        • Gold E.B.
        • et al.
        Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: the Study of Women's Health across the Nation (SWAN) Daily Hormone Study.
        J Clin Endocrinol Metab. 2004; 89: 2622-2631
        • Santoro N.
        • Crawford S.L.
        • Allsworth J.E.
        • Gold E.B.
        • Greendale G.A.
        • Korenman S.
        • et al.
        Assessing menstrual cycles with urinary hormone assays.
        Am J Physiol. 2003; 284: E521-E530
        • Brown J.R.
        • Skurnick J.
        • Sharma N.
        • Santoro N.
        Frequent intermittent ovarian function in women with premature menopause: a longitudinal study.
        Endocrine. 1993; 1: 467-474
        • Kassam A.
        • Overstreet J.W.
        • Snow-Harter C.
        • De Souza M.J.
        • Gold E.B.
        • Lasley B.L.
        Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm.
        Environ Health Perspect. 1996; 104: 408-413
        • Waller K.
        • Swan S.H.
        • Windham G.C.
        • Fenster L.
        • Elkin E.P.
        • Lasley B.L.
        Use of urine biomarkers to evaluate menstrual function in healthy premenopausal women.
        Am J Epidemiol. 1998; 147: 1071-1080
        • Park S.
        • Weiss G.
        • Skurnick J.
        • Wojtczuk A.
        • Goldsmith L.
        Characteristics of the urinary luteinizing hormone surge in young ovulatory women.
        Fertil Steril. 2007; 88: 684-690
        • Santoro N.S.
        • Brown J.R.
        • Adel T.
        • Skurnick J.H.
        Characterization of reproductive hormonal dynamics in the perimenopause.
        J Clin Endocrinol Metab. 1996; 81: 1495-1501
        • Hutton J.D.
        • Jacobs H.S.
        • Murray M.A.
        • James V.H.
        Relation between plasma oestrone and oestradiol and climacteric symptoms.
        Lancet. 1978; 1: 678-681
        • Prior J.C.
        Perimenopause: the complex endocrinology of the menopausal transition.
        Endocrine Rev. 1998; 19: 397-428
        • Reddy S.Y.
        • Warner H.
        • Guttuso T.
        • Messing S.
        • DiGrazio W.
        • Thornburg L.
        • et al.
        Gabapentin, estrogen and placebo for treating hot flushes.
        Obstet Gynecol. 2006; 108: 41-48
        • Rapkin A.J.
        Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment.
        Am J Obstet Gynecol. 2007; 196: 97-106
        • Freedman R.R.
        • Benton M.D.
        • Genik R.J.
        • Graydon F.X.
        Cortical activation during menopausal hot flashes.
        Fertil Steril. 2006; 85: 674-678
        • Board of Trustees of the North American Menopause Society
        Treatment of menopause-associated vasomotor symptoms: position statement of the North American Menopause Society.
        Menopause. 2004; 11: 11-33
        • NIH State-of-the-Science Panel
        National Institutes of Health state-of-the-science conference statement: management of menopause-related symptoms.
        Ann Intern Med. 2005; 142: 1003-1013