Time of Final Menstrual Period Predicted by New Model

Norra MacReady

March 26, 2013

A new model may help physicians determine how far a woman is from her final menstrual period (FMP).

With a better estimate of the FMP, physicians can start monitoring women for adverse developments, such as increased cardiovascular risk and accelerated bone loss, which precede the FMP by at least 1 year, lead author Gail A. Greendale, MD, and colleagues write in the April issue of the Journal of Clinical Endocrinology and Metabolism, published online March 26, 2013.

This, they say, "may also pave the way towards testing interventions designed to prevent rapid bone loss and architectural deterioration."

Dr. Greendale, of the Division of Geriatrics at the David Geffen School of Medicine, the University of California, Los Angeles, and coauthors developed a model that initially included measurements of estradiol (E2), follicle-stimulating hormone (FSH), and N-telopeptide (NTx). [Ed note: NTx discarded from final model.]

They analyzed data from women participating in the Study of Women's Health Across the Nation (SWAN), a longitudinal study designed to examine the transition to menopause in a community-based cohort. Women were eligible for SWAN if they were 42 to 53 years old, had an intact uterus and at least 1 ovary, were not pregnant or lactating, were not using drugs that affected ovarian function, had had at least 1 menstrual period in the 3 months prior to screening, and were white, African American, Hispanic, Chinese, or Japanese. The authors used baseline data collected from the women in 1996-1997 and from annual follow-up visits through 2006-2007.

Information on E2 and FSH levels was available on 554 women, and data on NTx were available for 472 of the participants. The authors studied hormone levels measured at 3 different times: 2 or more years prior to the FMP (the reference measurement); another measurement taken after the reference measurement but at least 2 years before the FMP; and a third measurement taken from 2 years before to 1 year after the FMP. The participants' age, height, weight, smoking status, and menstrual bleeding patterns also were assessed annually.

The investigators established when the women had crossed several landmarks: 2 years prior to the FMP, 1 year prior, and at the time of the FMP itself. They then determined whether fluctuations in hormone levels could be used as markers to signal when the participants had crossed each landmark.

At baseline, the mean age of the women was 45.6 years. The median reference level of FSH was 15.4 IU/L (standard deviation [SD], 11.7 - 22.1 IU/L). The median reference E2 level was 56.7 pg/ml, with an interquartile range (IQR) of 32.8 - 81.3 pg/ml. The median reference NTx measurement was 29.6 nanomoles of bone collagen equivalents per liter per millimole creatinine per liter (BCE/mM creatinine; IQR, 22.1 - 38.3 BCE/mM creatinine).

As the FMP approached, the ratio of current FSH level to the reference value became larger, and the ratio of current E2 level to the reference value became smaller. The NTx ratio also became larger over time, but the changes were small, and it was discarded from the final model. The magnitude of change in the FSH ratio was "substantially" larger than the changes in the E2 or NTx ratios.

In the final model, which included FSH and E2 data, the areas under the curves predicted that the probability of a woman's being 2 years away from FMP was .902; 1 year away, .926, and having experienced her FMP, .945. "To our knowledge, no studies have articulated the goal of discerning whether a woman has reached 1 year prior to FMP, the time at which we previously found that rapid bone loss begins," the authors write.

"We need a better way to answer women's questions about when to expect the final menstrual period," Dr. Greendale said in a press release. "If further research bears out our approach, it could be the first step to developing Web-based calculators and other tools women can use to estimate where they are in the menopause transition and how far away their final period is."

The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), the Department of Health and Human Services through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH). The authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online March 26, 2013.