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Male preference for younger women explains today’s menopausal age

Among several evolutionary explanations for the menopause, the most frequently heard is that female longevity has overtaken the point at which women cease to become fertile. The fixed stock of ovarian follicles has simply depleted long before death, and chronological ageing has progressed more slowly than ovarian ageing. So today, most women in developed countries can expect around 30 years of active life after the menopause, even though that activity excludes the ability to conceive and deliver a baby. And one anthropological reason why that cut-off age has for so long been fixed at around 50 is that women giving birth at an older age would not have the ability to help their children grow and become adults.

In terms of evolutionary theory, according to a recent report, this has prompted two explanations for the menopause: trade-offs between prolonged life span and reproduction; and fitness benefits for older, non-reproductive women through increasing the reproductive success of their offspring (the “grandmother effect” whereby older women must not look after their own children but are fit enough to help their grandchildren).¹ This same report, however, has now suggested a third evolutionary explanation for the menopause – that human male “mating preference” for younger women has led to the accumulation of gene mutations which are incompatible with female fertility, and thus to the menopause. As ever, it is the man who gets the blame.

The theory was tested in a “two-sex computational model” which showed that “neither an assumption of pre-existing diminished fertility in older women nor a requirement of benefits derived from older, non-reproducing women assisting younger women in rearing children” is necessary to explain the origin of menopause.

Instead, this complicated model was based on an evolving population with constant size, without pre-existing diminished fertility in females, and incorporating mutations that affected fertility as well as mortality. However, only when a matrix involving male preference for younger females was added to the model did female-specific mutations with a late age of onset begin to accumulate in the population – otherwise infertility-causing mutations did not accumulate, fertility and survival remained high, and there was no menopause. Indeed, the model suggested that, if the matrix were to encode female preference for younger males (rather than male preference for younger females), the role of the sexes would be reversed. “Male menopause never arose because male-specific infertility-causing mutations were subjected to purifying selection and did not accumulate,” the investigators propose. Only in women did the fertility mutations arise and accumulate.

Bringing this futuristic model back down to earth, one of the investigators, evolutionary geneticist Professor Rama Singh from McMaster University in Canada, told reporters that men choosing younger partners were “stacking the odds” against continued fertility. Conversely, however, he also suggested that the most recent trend for later motherhood might eventually extend the age of menopause, as fertility-associated gene mutations in older age were absorbed into the gene pool.

Morton RA, Stone JR and Singh RS. Mate choice and the origin of menopause. PLoS Comput Biol 2013; 9: e1003092.

No adverse – or beneficial – effect of HRT on cognitive function in younger postmenopausal women

Ten years after the Women’s Health Initiative Memory Study (WHIMS) controversially reported that combined hormone therapy in women over 65 was associated with a much greater risk of dementia than placebo, a further study in younger women (aged 50 to 55) continues to find no benefit in the incidence of dementia from postmenopausal hormones.^1,2

The original WHIMS study of 2003 had enrolled almost 5000 women from the WHI into a separate trial designed to assess the effect of combined hormone therapy (HRT) and placebo on “probable” dementia and mild cognitive impairment. All the women were over 65, and results showed that the risk of probable dementia in the HRT users doubled over a study period of 4.05 years (HR 2.05). While there was no significant effect on mild cognitive impairment with hormone therapy, there was some indication of an increased risk of “clinically meaningful” cognitive decline among women on active treatment. Imaging tests even found that the brains of those on HRT had become smaller when compared with those of women taking placebo. Mainly as a result of this study dementia, alongside heart disease, stroke and breast cancer, remains one of four risks still formally associated with HRT use in the US.

The latest study (WHIMS in younger women, WHIMSY) was performed in 1326 postmenopausal women who had originally taken part in the combined or unopposed WHI trials (for a mean period of seven years) when they were aged between 50 and 55. Results showed that cognitive function scores from women formerly assigned to HRT were similar to those of the women on placebo, a mean intervention effect of 0.02 (−0.08 to 0.12) standard deviation units. Similarly, no overall differences were found for any individual cognitive domain.

Drawing conclusions, the authors stated: “Our findings provide reassurance that [estrogen]-based therapies when administered to women earlier in the postmenopausal period do not seem to convey long-term adverse consequences for cognitive function. Although we cannot rule out acute benefits or harm, these do not appear to be present to any degree a mean of seven years after cessation of therapy.”

In a JAMA editorial accompanying the report, US epidemiologist Francine Grodstein of Brigham and Women’s Hospital, Boston, described the findings as “reassuring,” adding (for the news agency Reuters) that “this study didn’t find hormone therapy had the amount of harm as it did for older women.”

One of the WHIMSY investigators also offered to Reuters a possible explanation for the discrepancy in age-related findings between the two studies – that older women already have more memory problems and HRT may simply accelerate the decline. “It could also be,” Reuters reported, “that a woman's brain adapts to lower levels of hormones after menopause and hormone therapy disrupts that process”.

Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003; 289: 2651–2662.

IMS updates its recommendations on the use of HRT

A report from an international consensus meeting on postmenopausal hormone therapy (HRT) staged last year concluded that

HRT is the most effective treatment for symptoms related to the hormonal changes of menopause, is also beneficial for bone health, and may decrease cardiovascular disease.

The consensus was drawn up by several societies, including the North American Menopause Society and International Menopause Society (IMS), which also organised the meeting. Following the consensus, the IMS updated its own recommendations on the use of HRT and concluded that the HRT pendulum has now “swung back from its peak negative sentiment” and returned to a more rational evidence-based approach.²

The 21-page report is extensive in its scope, but in outline follows largely in the footsteps of the global consensus – that is, that HRT is the most effective treatment for menopausal symptoms and that its use in healthy women under 60 years of age or within 10 years of menopause will not increase the risk of coronary events. In addition, there are extensive sections on the benefits of HRT (notably osteoporosis prevention and cardiovascular disease), potentially serious adverse effects (breast and endometrial cancers, and venous thromboembolism), vaginal atrophy, alternative treatments, lifestyle, cognitive function, and sexuality.

From these sections the IMS recommends that

Local low-dose estrogen therapy is preferred for women whose symptoms are limited to vaginal dryness or associated discomfort with intercourse.

Weight gain after stopping smoking may modify the health benefits

Medicine today, despite its penchant for clear evidence-based guidance, still has its fair share of paradoxes. The most frequently talked of is the obesity paradox, whereby moderately overweight patients – particularly those with heart failure – appear to have a better chance of survival than those who are lean and frail. The finding, as reported in many studies, is a contradiction to all our prevailing concepts of cardiovascular prevention, but cannot be denied in certain cases.

There have been suggestions of a similar paradox in the case of smoking that the weight gain and diabetes which follow after stopping smoking may be more than enough to counteract any health benefits otherwise achieved.

This potential paradox has now been tested in the huge database of the Women’s Health Initiative, and particularly in the 3381 (from 100,000+) women who developed coronary heart disease (CHD) over a follow-up period of eight years. This latest analysis found that non-smoking was indeed associated with an overall lower risk of CHD in postmenopausal women either with or without diabetes.¹ The incidence rates per 1000 person-years were 3.3 in never smokers, 3.7 in former smokers, 7.6 in current smokers, and 5.3 in those who had newly quit.

However, weight gain following smoking cessation did weaken this association, especially for women with diabetes who gained 5 kg or more over the study period. For women who gained less than 5 kg, the association between smoking status and CHD risk was similar to the overall results in both women with and without diabetes.

Luo J, Rossouw J and Margolis KL. Smoking cessation, weight change, and coronary heart disease among postmenopausal women with and without diabetes. JAMA 2013; 310: 94–96.