By Tori Hudson, ND

Predicting Age of Menopause Onset

Current methods of predicting final menstrual period are not very accurate. They can only predict final menstrual period (FMP) to within four years. These methods include measuring menstrual bleeding patterns and follicle stimulating hormone (FSH).  Measuring FSH indirectly measures ovarian reserve; but levels vary widely across the menstrual cycle, and even within a given day. 

Anti-mullerian hormone (AMH), produced in the ovarian follicles, slowly but continuously decreases as the number of follicles declines.  AMH generally stays stable and is also increasingly being used although previous tests have not been very precise; however, a new ultrasensitive AMH test that is providing a much lower detection limit is considered more accurate (1.85 pg/mL, compared with 50 to 100 pg/mL).

Lower serum AMH levels, high serum FSH levels, and low antral follicle count (AFC) are associated with the onset of menopause; but it is unclear which of these measures or combination of measures best predicts menopause.  In the updated 2011 STRAW + 10 analysis of newer studies, the authors deemed cycle day 3 FSH levels greater than 25 IU/L characteristic of the late menopause transition and associated with onset of menopause within one to three years. 

The 2013 analysis of the CARDIA women’s study showed that an antral follicle count of 4 or lower independently predicted menopause within seven years.

In another study, Nair and colleagues showed that an AMH of less than 0.5 ng/dL was independently associated with natural menopause.

This evolving story of the value of screening
mammography and resulting guidelines will continue to
slowly change based on a more individualized approach.

The AMH test is one of the most common hormones used in estimating a woman’s fertility and is often used during fertility treatments like in-vitro fertilization (IVF). The level of AMH measured for that purpose (measured in ng/mL) is often 1000-fold higher than the levels measured by the ultrasensitive test in order to determine the time to final menstrual period.

It took the SWAN study (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 data necessary to be able to demonstrate the predictive value of AMH.   Results showed that the ultrasensitive AMH test had significantly better accuracy for predicting final menstrual period within the next two years compared to FSH, as well as the next three years. 

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.

If AMH <10 pg/mL, the probability of having a final menstrual period (FMP) in the next 12 months ranged from 51% for those <48 years old to 79% for those aged 51 years or older.

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

For 38% of samples, AMH levels were >100 pg/mL: 65% for women younger than 48 and 27% for women aged 51 or older. The specifics for not having a FMP in the next 12 months ranged from 65% for women <48 years old to 27% for women 51 or older. For these aged groups, the negative predictive values ranged from 97% to 90%.

The level of AMH fluctuates much less over the course of menstruation than FSH, LH, estrogen, and progesterone, so it won’t change much based on which day you took this test. The chart below shows typical changes in AMH levels with age. 

Does Screening Mammography Reduce Breast Cancer Mortality??

According to this Australian study covering the last three decades, it looks like the answer is “no.” Rather, it is adjuvant therapy for breast cancer patients that reduces mortality.  Breast cancer screening’s primary goal is to identify women with early breast cancers, stages I or II.  The principle is based on the assertion that early detection and thus early treatment results in reduced incidence of advanced malignancies and thus, saves lives.   The results of this study seriously challenge that paradigm.  In addition, other studies in the last few years, have resulted in changes in screening guidelines as well as confusion and differences in recommendations amongst different organizations.

The current study assessed the relative influences of screening mammography and adjuvant therapy on breast cancer mortality trends by analyzing data from cancer registries and mammographic results for 76,630 women with invasive breast cancer in an Australian region that offers screening every two years for women ages 50-69 over a period from 1982 through 2013. In that age group, screening rates increased from 48% in 1994 to 57% in 2012.  By 1999, they report that 74% of women with early stage breast cancers were receiving tamoxifen and the use of adjuvant chemotherapy was 72% for premenopausal women and 29% for postmenopausal women.  In the time period of the study, breast cancer mortality fell from 32 per 100,000 in 1982 to 24 per 100,000 in 2013.  Unfortunately, the incidence of advanced breast cancer rose from 12 per 100,000 in 1986 to 24 per 100,000 in 2013.

Commentary:   It has been generally presumed for decades that screening mammography and early detection of breast cancer plays an essential role in the declining mortality of breast cancer.  However, important studies in the US in 2012 (NEJM  2012 Nov 22; 367:1998, and NEJM 2012;367:1998) and in the Netherlands (BMJ 2017;359:j5224) actually found that the incidence of advanced breast cancer was stable or increased after screening mammography was introduced.  The researchers of the current Australian study concluded that the reduced mortality from breast cancer in women in that region can be entirely due to the increased utilization of adjuvant therapy and that the increase in the incidence of advanced breast cancer rules out a direct association of mammography screening with a decline in mortality.   They then proposed a radical shift in medical practice and that government-sponsored programs for screening mammography be discontinued. 

This evolving story of the value of screening mammography and resulting guidelines will continue to slowly change based on a more individualized approach, taking into account age and other distinguishing, known breast cancer risk factors such as first degree relative with a history of breast cancer, pregnancy/birthing history, hormone therapy, alcohol, exercise and weight history…and maybe eventually, even nutrition. 

Burton R, Stevenson C.  Assessment of breast cancer mortality trends associated with mammography mortality trends associated with mammographic screening and adjuvant therapy from 1986 to 2013 in the State of Victoria, Australia.  JAMA NetwOpen 2020 June 1;3:e208249.