(1) Can menstrual cycle characteristics predict early menopause?
The US Nurses’ Health Study is well placed to follow a large cohort of women over time and a recent publication from this study has linked menstrual cycle characteristics in adolescence and early adulthood with eventual early menopause . In over 108,000 premenopausal women studied from a baseline age of 25–42 years, from the years 1989 to 2011, 2.6% of participants (n = 2794) underwent an early menopause (< 45 years) during follow-up. The authors of the paper reported that menarche at age 10 years (compared with 12 years) was a risk factor for early menopause, with a hazard ratio (HR) of 1.19 (95% CI 1.02–1.39). Other factors that were linked with an early menopause included cycle length < 25 days in early adulthood (18–22 years), with a HR of 1.71 (95% CI 1.47–1.96). Those with irregular cycles had a reduced risk of early menopause, HR 0.51 (95% CI 0.43–0.60), and women with a cycle length in early adulthood of ≥ 40 days had a similar reduction in risk of undergoing early menopause, HR 0.44 (95% CI 0.34–0.58). Hence it appears that factors that are associated with a higher frequency of ovulation at least early in reproductive life (and potentially throughout reproductive life if the pattern continues long term) may in fact be linked to an early menopause, with the reverse being true for those undergoing less frequent ovulation.
In most cases of premature or early menopause, a causative factor will not be found, which can be perplexing for women searching for answers for themselves and possibly also for their female children, who may also be at risk of undergoing menopause at a similar or even younger age. Hence the importance of research that attempts to find patterns or links that may point to markers that may be used to identify women at risk of undergoing an early or premature menopause.
(2) Statins: effects on bone density
Women with osteoporosis commonly have other co-morbidities and are often on medications that may impact on bone health. Whilst considerable focus has been directed toward treatments with deleterious effects on bone, other non-osteoporosis medications may have favorable effects on bone turnover. This study in over 45,000 users of statins, compared to over 115,000 controls, included over 68,000 women, with an age range of 50–90 years . Follow-up occurred over a 13-year period. 10% of the cohort overall developed osteoporosis: 6.8% of statin users and 11.3% of non-users, with a hazard ratio of developing osteoporosis in statin users of 0.52 (95% CI 0.49–0.54). When the individual statin products were examined, simvastatin, atorvastatin and rosuvastatin were all associated with a lower risk of developing osteoporosis (HR 0.85, 95% CI 0.76–0.94; HR 0.68, 95% CI 0.63–0.74; HR 0.43, 95% CI 0.36–0.52, respectively). No reduction in risk was seen for pravastatin, however: HR 0.89 (95% CI 0.76–1.05).
The authors highlighted the facts that statins augment osteoblast activity and inhibit osteoblast apoptosis and increase bone formation, in addition to sharing the same pathway as nitrogen-containing bisphosphonates. Furthermore, it has been reported that simvastatin has been shown to inhibit RANKL-induced osteoclast differentiation.
(3) Different effect of BMI on premenopausal and postmenopausal breast cancer risk
This article examined the findings from 31 prospective cohort studies of women between 30 and 79 years and involved over 3.3 million women . The authors reported that there was no relationship between BMI and breast cancer risk in premenopausal women; however, in postmenopausal women, breast cancer risk increased by 3.4% for every 1 kg/m2 increment in BMI. When exploring the relationship between BMI and breast cancer further, the authors reported a reduction in risk of breast cancer with increasing BMI in studies of European women (relative risk (RR) 0.79, 95% CI 0.70–0.88) but not in Asian or American women, or the group as a whole. However, in postmenopausal women, higher BMI was associated with higher risks of breast cancer in the group as a whole, Asian women (RR 2.10; 95% CI 1.64–2.69), US women (RR 1.29; 95% CI 1.14–1.46), women with estrogen receptor-positive breast cancer (RR 1.32; 95% CI 1.23–1.42) and those with no past hormone therapy use (RR 1.43; 95% CI 1.21–1.68), but interestingly no increase in risk with increasing BMI in European women (RR 1.19; 95% CI 0.98–1.43) or those with a past history of hormone therapy use (RR 0.94; 95% CI 0.63–1.40).
Increasingly cancer risk has been linked to lifestyle, and, whilst there are very clear links with regard to obesity and some cancers in women, such as endometrial cancer, the relationship between BMI per se and some cancers is yet to be fully defined. Fat is an endocrinologically active organ, especially with regard to estrogen, and hence a link between increased fat mass and hormonally linked cancers seems logical. These findings are interesting and point to the importance of lifestyle and metabolic factors in breast cancer risk, and also to the role of health practitioners in promoting general health measures such as achieving a healthy weight for height, as a cancer risk reduction strategy.
Endocrinologist, Women’s Health Research Program, Monash University, Australia
Whitcomb BW, Purdue-Smithe A, Hankinson SE, Manson JE, Rosner BA, Bertone-Johnson ER. Menstrual cycle characteristics in adolescence and early adulthood are associated with risk of early natural menopause. J Clin Endocrinol Metab 2018;103:3909-18
Lin TK, Chou P, Lin CH, Hung YJ, Jong GP. Long-term effect of statins on the risk of new-onset osteoporosis: A nationwide population-based cohort study. PLoS One 2018;13:e0196713
Chen Y, Liu L, Zhou Q, et al. Body mass index had different effects on premenopausal and postmenopausal breast cancer risks: a dose-response meta-analysis with 3,318,796 subjects from 31 cohort studies. BMC Public Health 2017;17:936