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Date of release: 15 August, 2016

Anti-Müllerian hormone and prediction of age at natural menopause

Since the timing of the onset of the last menstrual period in a woman’s life varies, less between cultures, but more individually, it has induced a universal challenge on how to predict the age at natural menopause (ANM). Fertility issues in women raise concerns for those who postpone their reproduction due to educational and professional goals. Anti-Müllerian hormone (AMH) seems to have a certain predictive role not only in ANM, ovarian reserve tests, premature ovarian insufficiency, assisted reproduction techniques but also in different clinical conditions such as polycystic ovary syndrome, ovarian surgery, granulosa cell tumors, cancer treatment, anorexia nervosa [1]. That is why the dynamics of AMH have been widely investigated by many groups; one of the intriguing issues is whether we can predict age at natural menopause using ovarian reserve tests or the mother's age at menopause. Depmann and colleagues recently published a study and a review of the current literature [2, 3]. The review, which included six studies, was summarized as follows: 'AMH is currently the most promising marker for ANM prediction. The predictive capacity of mother's ANM demonstrated in a single study makes this marker a promising contributor to AMH for menopause prediction. Models, however, do not predict the extremes of menopause age very well and have a wide prediction interval. These markers clearly need improvement before they can be used for individual prediction of menopause in the clinical setting.'

Comment

The above quoted researchers [2, 3] recruited 265 normo-ovulatory women (21–46 years old) between 1992 and 2001. At the end of follow-up, 2009–2013, 155 women remained for analysis and 37.5% of them had become postmenopausal. AMH, follicle stimulating hormone (FSH) and the antral follicle count were checked at baseline and follow-up. Examinees did not differ in age at menarche and body mass index and active smoking from the initial collection of data until the last follow-up visit. Multivariate analysis corrected for age and both smoking at baseline and follow-up period showed that the antral follicle count and FSH lost their predictive capacity in models which included female age and smoking behavior, while AMH remained capable of predicting time to menopause. The authors concluded that, although age-specific AMH is significantly capable of predicting time to menopause, making it a possible candidate in the preventive management of age-related infertility, a reduced predictive effect of AMH was observed with increasing age of the woman in extreme age ranges of menopause prediction, and AMH should not be used to make individual forecasts of menopause.

On the other hand, there is a promising role for a combination of parameters to predict time to menopause, age at natural menopause and risk for developing diseases linked to menopause as well. Although the mother’s age at natural menopause, even used in combination with AMH, does not improve prediction of individual age at natural menopause, quantification with a net reclassification index suggests that a 47% improvement in predictive accuracy is offered by adding AMH to the model of age and mother's age at natural menopause, i.e. both parameters have added value in forecasting [4].

In addition, environmental factors, sociodemographic features, and lifestyle habits can influence a woman’s age at natural menopause [5], while genome-wide linkage analyses, candidate gene association studies and genome-wide association studies indicate that menopause is a tightly regulated biological process under distinct genetic control [6].

In conclusion, there is growing evidence that a combination of anti-müllerian hormone, antral follicle count and mother’s age at menopause [2], with possible new additional parameters, may become the basis for developing a new and practical algorithm with a simple scoring system to predict individual age at natural menopause. A very close model was recently proposed by Gohari and colleagues [7], where a more precise calculation technique based on AMH was proposed. Since each woman has her own specific AMH trajectory, consecutive AMH measurements will enable medical practitioners to individualize prediction of menopause.

Comentario

Ivan Fistonić


President of Institute for Women’s Health, Zagreb, Croatia; Professor at University of Applied Health Sciences, Zagreb, Croatia; Assistant Professor at University Department of Health Studies, University of Split, Split, Croatia



    References

  1. Nelson SM. Biomarkers of ovarian response: current and future applications. Fertil Steril 2013;4:963-9


    http://www.ncbi.nlm.nih.gov/pubmed/23312225

  2. Depmann M, Broer SL, van der Schouw YT, et al. Can we predict age at natural menopause using ovarian reserve tests or mother's age at menopause? Menopause 2016;23:224-32


    http://www.ncbi.nlm.nih.gov/pubmed/26372034

  3. Depmann M, Eijkemans MJ, Broer SL, et al. Does anti-Müllerian hormone predict menopause in the general population? Results of a prospective ongoing cohort study. Hum Reprod 2016;31:1579-87


    http://www.ncbi.nlm.nih.gov/pubmed/27179263

  4. Dólleman M, Depmann M, Eijkemans MJ, et al. Anti-Mullerian hormone is a more accurate predictor of individual time to menopause than mother's age at menopause. Hum Reprod 2014;29:584–91


    http://www.ncbi.nlm.nih.gov/pubmed/24435779

  5. Richardson MC, Guo M, Fauser BC, Macklon NS. Environmental and developmental origins of ovarian reserve. Hum Reprod Update 2014;3:353-69


    http://www.ncbi.nlm.nih.gov/pubmed/24287894

  6. Daan NM, Fauser BC. Menopause prediction and potential implications. Maturitas 2015;82:257–65


    http://www.ncbi.nlm.nih.gov/pubmed/26278873

  7. Gohari MR, Ramezani Tehrani F, Chenouri S, Solaymani-Dodaran M, Azizi F. Individualized predictions of time to menopause using multiple measurements of antimüllerian hormone. Menopause 2016 Jun 20. Epub ahead of print


    http://www.ncbi.nlm.nih.gov/pubmed/27326817