Use of antimüllerian hormone to predict the menopausal transition in HIV-infected women


      HIV infection has been associated with early menopausal onset, which may have adverse long-term health consequences. Antimüllerian hormone, a biomarker of ovarian reserve and gonadal aging, is reduced in HIV-infected women.


      We sought to assess the relationship of antimüllerian hormone to age of menopause onset in HIV-infected women.

      Study Design

      We used antimüllerian hormone levels measured in plasma in 2461 HIV-infected participants from the Women’s Interagency HIV Study to model the age at final menstrual period. Multivariable normal mixture models for censored data were used to identify factors associated with age at final menstrual period.


      Higher antimüllerian hormone at age 40 years was associated with later age at final menstrual period, even after multivariable adjustment for smoking, CD4 cell count, plasma HIV RNA, hepatitis C infection, and history of clinical AIDS. Each doubling of antimüllerian hormone was associated with a 1.5-year increase in the age at final menstrual period. Median age at final menstrual period ranged from 45 years for those in the 10th percentile of antimüllerian hormone to 52 years for those in the 90th percentile. Other factors independently associated with earlier age at final menstrual period included smoking, hepatitis C infection, higher HIV RNA levels, and history of clinical AIDS.


      Antimüllerian hormone is highly predictive of age at final menstrual period in HIV-infected women. Measuring antimüllerian hormone in HIV-infected women may enable clinicians to predict risk of early menopause, and potentially implement individualized treatment plans to prevent menopause-related comorbidities and to aid in interpretation of symptoms.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Calvet G.A.
        • Grinsztejn B.G.
        • Quintana Mde S.
        • et al.
        Predictors of early menopause in HIV-infected women: a prospective cohort study.
        Am J Obstet Gynecol. 2015; 212: 765.e1-765.e13
        • de Pommerol M.
        • Hessamfar M.
        • Lawson-Ayayi S.
        • et al.
        Menopause and HIV infection: age at onset and associated factors, ANRS CO3 Aquitaine cohort.
        Int J STD AIDS. 2011; 22: 67-72
        • Schoenbaum E.E.
        • Hartel D.
        • Lo Y.
        • et al.
        HIV infection, drug use, and onset of natural menopause.
        Clin Infect Dis. 2005; 41: 1517-1524
      1. Centers for Disease Control. Diagnoses of HIV infection–United States and dependent areas–2013. HIV surveillance report, 2014. Available at: Accessed October 06, 2016.

      2. Kaiser Family Foundation. The global HIV/AIDS epidemic, 2015. Available at: Accessed November 25, 2015.

        • Gallagher J.C.
        Effect of early menopause on bone mineral density and fractures.
        Menopause. 2007; 14: 567-571
        • Rocca W.A.
        • Shuster L.T.
        • Grossardt B.R.
        • et al.
        Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging.
        Womens Health (Lond). 2009; 5: 39-48
        • Shuster L.T.
        • Rhodes D.J.
        • Gostout B.S.
        • Grossardt B.R.
        • Rocca W.A.
        Premature menopause or early menopause: long-term health consequences.
        Maturitas. 2010; 65: 161-166
        • Bouman A.
        • Heineman M.J.
        • Faas M.M.
        Sex hormones and the immune response in humans.
        Hum Reprod Update. 2005; 11: 411-423
        • Kim C.
        • Cushman M.
        • Kleindorfer D.
        • Lisabeth L.
        • Redberg R.F.
        • Safford M.M.
        A review of the relationships between endogenous sex steroids and incident ischemic stroke and coronary heart disease events.
        Curr Cardiol Rev. 2015; 11: 252-260
        • Sabin C.A.
        • Smith C.J.
        • d'Arminio Monforte A.
        • et al.
        Response to combination antiretroviral therapy: variation by age.
        AIDS. 2008; 22: 1463-1473
        • van Benthem B.H.
        • Vernazza P.
        • Coutinho R.A.
        • Prins M.
        • European Study on the Natural History of HIV Infection in Women and the Swiss HIV Cohort Study
        The impact of pregnancy and menopause on CD4 lymphocyte counts in HIV-infected women.
        AIDS. 2002; 16: 919-924
        • van Benthem B.H.
        • Vernazza P.
        • Coutinho R.A.
        • Prins M.
        Impact of pregnancy and menopause on CD4 cell counts.
        J Acquir Immune Defic Syndr. 2005; 38: S22
        • Villa E.
        • Karampatou A.
        • Camma C.
        • et al.
        Early menopause is associated with lack of response to antiviral therapy in women with chronic hepatitis C.
        Gastroenterology. 2011; 140: 818-829
        • Scherzer R.
        • Bacchetti P.
        • Messerlian G.
        • et al.
        Impact of CD4+ lymphocytes and HIV infection on anti-mullerian hormone levels in a large cohort of HIV-infected and HIV-uninfected women.
        Am J Reprod Immunol. 2015; 73: 273-284
        • Freeman E.W.
        • Sammel M.D.
        • Lin H.
        • Gracia C.R.
        Anti-mullerian hormone as a predictor of time to menopause in late reproductive age women.
        J Clin Endocrinol Metab. 2012; 97: 1673-1680
        • van Disseldorp J.
        • Faddy M.J.
        • Themmen A.P.
        • et al.
        Relationship of serum antimullerian hormone concentration to age at menopause.
        J Clin Endocrinol Metab. 2008; 93: 2129-2134
        • Broer S.L.
        • Eijkemans M.J.
        • Scheffer G.J.
        • et al.
        Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women.
        J Clin Endocrinol Metab. 2011; 96: 2532-2539
        • Freeman E.W.
        • Sammel M.D.
        • Lin H.
        • Boorman D.W.
        • Gracia C.R.
        Contribution of the rate of change of antimullerian hormone in estimating time to menopause for late reproductive-age women.
        Fertil Steril. 2012; 98: 1254-1259.e1-2
        • Schoenaker D.A.
        • Jackson C.A.
        • Rowlands J.V.
        • Mishra G.D.
        Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents.
        Int J Epidemiol. 2014; 43: 1542-1562
        • Gold E.B.
        • Bromberger J.
        • Crawford S.
        • et al.
        Factors associated with age at natural menopause in a multiethnic sample of midlife women.
        Am J Epidemiol. 2001; 153: 865-874
        • Bacon M.C.
        • von Wyl V.
        • Alden C.
        • et al.
        The Women's Interagency HIV study: an observational cohort brings clinical sciences to the bench.
        Clin Diagn Lab Immunol. 2005; 12: 1013-1019
      3. Centers for Disease Control and Prevention. HIV/AIDS surveillance report. Vol 2. 1994. Available at: Accessed October 6, 2016.

      4. Centers for Disease Control and Prevention. HIV/AIDS surveillance report. Vol 13. Atlanta (GA): US Department of Health and Human Services; 2001.

      5. Centers for Disease Control and Prevention. HIV surveillance report. Vol 21. 2009. Available at: Accessed October 6, 2016.

        • Iwase A.
        • Nakamura T.
        • Nakahara T.
        • Goto M.
        • Kikkawa F.
        Anti-mullerian hormone and assessment of ovarian reserve after ovarian toxic treatment: a systematic narrative review.
        Reprod Sci. 2015; 22: 519-526
        • Mistler S.A.
        SAS macro for applying multiple imputation to multilevel data.
        Proc SAS Global Forum, San Francisco (CA)2013
        • Gilks W.R.
        • Richardson S.
        • Spiegelhalter D.J.
        Markov chain Monte Carlo in practice.
        in: Chapman and Hall/CRC, London1995
        • Boldsen J.L.
        • Jeune B.
        Distribution of age at menopause in two Danish samples.
        Hum Biol. 1990; 62: 291-300
        • Hoeting J.A.
        • Madigan D.
        • Raftery A.E.
        • Volinsky C.T.
        Bayesian model averaging: a tutorial.
        Stat Sci. 1999; 14: 382-401
        • Depmann M.
        • Faddy M.J.
        • van der Schouw Y.T.
        • et al.
        The relationship between variation in size of the primordial follicle pool and age at natural menopause.
        J Clin Endocrinol Metab. 2015; 100: E845-E851
        • Cieloszyk K.
        • Hartel D.
        • Moskaleva G.
        • Schoenbaum E.E.
        Effects of hepatitis C virus infection on menopause status and symptoms.
        Menopause. 2009; 16: 401-406
        • Di Martino V.
        • Lebray P.
        • Myers R.P.
        • et al.
        Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure.
        Hepatology. 2004; 40: 1426-1433
        • Cengiz M.
        • Ozenirler S.
        • Yilmaz G.
        Estrogen receptor alpha expression and liver fibrosis in chronic hepatitis C virus genotype 1b: a clinicopathological study.
        Hepat Mon. 2014; 14: e21885
        • Hanafi N.F.
        • Abo Ali A.H.
        • Abo el kheir H.F.
        ICSI outcome in women who have positive PCR result for hepatitis C virus.
        Hum Reprod. 2011; 26: 143-147
        • Englert Y.
        • Moens E.
        • Vannin A.S.
        • et al.
        Impaired ovarian stimulation during in vitro fertilization in women who are seropositive for hepatitis C virus and seronegative for human immunodeficiency virus.
        Fertil Steril. 2007; 88: 607-611
        • Tsepelidis S.
        • Devreker F.
        • Demeestere I.
        • Flahaut A.
        • Gervy C.
        • Englert Y.
        Stable serum levels of anti-mullerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women.
        Hum Reprod. 2007; 22: 1837-1840
        • Griliches Z.
        • Ringstad V.
        Error-in-the-variables bias in nonlinear contexts.
        Econometrica. 1970; 38: 368-370
        • Brooks J.T.
        • Buchacz K.
        • Gebo K.A.
        • Mermin J.
        HIV infection and older Americans: the public health perspective.
        Am J Public Health. 2012; 102: 1516-1526