Ultrasensitive Test Better Predicts Final Menstrual Period

A new way of more precisely measuring anti-Müllerian hormone (AMH) in women's blood may predict menopause and final menstrual period to within a window of 1 to 2 years, much better than current methods. Results were published online January 22 in the Journal of Clinical Endocrinology and Metabolism.

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AMH is produced by developing follicles in the ovary and may indicate ovarian reserve, or the number of eggs a woman has left in her ovaries. Ovarian reserve decreases with age as menopause approaches.

Current methods of predicting final menstrual period are not very accurate ― they can only predict final menstrual period to within 4 years. These methods include measuring menstrual bleeding patterns and follicle stimulating hormone (FSH). Measuring FSH indirectly measures ovarian reserve; levels vary widely across the menstrual cycle, making results difficult to interpret. AMH generally stays stable and is also used, although previous AMH tests have not been very precise. The current study employed a new, ultrasensitive AMH test that used a two-site ELISA with a much lower detection limit than those used in current AMH tests (1.85 pg/mL, compared with 50 to 100 pg/mL).

"Researchers have long thought AMH would be a superior marker of the time to menopause, but tests haven't been sensitive enough to detect the very, very low levels that occur in the year or two leading up to menopause," author Joel Finkelstein, MD, said in a news release. Finkelstein is affiliated with Massachusetts General Hospital in Boston.

"It took a cohort like the Study of Women's Health Across the Nation, which followed the same women year after year from well before menopause until well after, to get the kind of data necessary to be able to demonstrate the predictive value of AMH," he said.

The study enrolled women from 1996 to 1998 at seven clinical sites across the United States. It included 7407 blood samples from 1537 pre- or early perimenopausal women whose mean age was 47.5 years. Of these, 49.5% (761/1537) were white, 29.9% were black (460/1537), 18.6% (286/1537) were Hispanic, 9.5% (146/1537) were Chinese, and 11% (170/1537) were Japanese. The researchers measured hormone levels (FSH, AMH, inhibins, and estradiol) every 12 months until women stopped having their periods for at least 12 months (final menstrual period).

Results showed that the ultrasensitive AMH test had significantly better accuracy for predicting final menstrual period within the next 2 years compared to FSH (area under the curve [AUC], 0.891 and 0.877, respectively; P < .05), as well as the next 3 years (AUC, 0.896 and 0.871, respectively; P < .05). About the same degree of accuracy was achieved with AMH and FSH at 12 months (AUC, 0.881 and 0.885, respectively; P = NS).

For women with an AMH <10 pg/mL, the probability of having a final menstrual period in the next 12 months ranged from 51% for those younger than 48 years to 79% for those aged 51 years or older.

For 36% of samples (2675/7407), AMH levels were <10 pg/mL. The sensitivities for having a final menstrual period with an AMH <10 pg/mL ranged from 71% for women younger than 48 years to 82% for women aged 51 years or older. For these age groups, positive predictive values ranged from 51% to 79%.

For 38% percent of samples (2839/7407), AMH levels were >100 pg/mL. The specificities for not having a final menstrual period in the next 12 months with AMH >100 pg/mL ranged from 65% for women younger than 48 years to 27% for women aged 51 or older. For these age groups, negative predictive values ranged from 97% to 90%.

For women with AMH >100 pg/mL, the probability of not having a final menstrual period in the next 12 months ranged from 97% for those younger than 48 years to 90% for those 51 years or older.

"Another Exciting Step Towards Personalization of Women's Reproductive Health"

"In general, this study is another exciting step towards personalization of women's reproductive health. It would be interesting to see whether incorporation of additional parameters known to be associated with menopause, such as family history and smoking, can further enhance the ability to predict a woman's menopause," Reshef Tal, MD, PhD, told Medscape Medical News via email. Tal is an assistant professor at Yale School of Medicine.

He went on to discuss several potential clinical implications of the study. The ultrasensitive AMH test may help differentiate women who are approaching menopause from those who are not having periods for other reasons, such as stress or hormone imbalance. It may also help better diagnose women who have gone through menopause but who are experiencing vaginal bleeding for other reasons, such as fibroids or cancer. The test may also help women decide between hysterectomy or medical management of fibroids.

He also noted several limitations of the study. For example, AMH may vary throughout the menstrual cycle in up to 15% of women, but the researchers only measured one AMH level for many women in this study. Also, although the study included women from diverse racial and ethnic backgrounds, it did not include women younger than 42, so the findings, and especially the AMH cutoffs, do not apply to younger women who show decreasing ovarian reserve.

Nevertheless, he added: "I think that this AMH test has great potential to be clinically useful in late reproductive age women, but development of a reliable automated standardized assay with the ultrasensitive platform would be necessary before it is quite ready for routine clinic use."

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