Thursday, January 28, 2016

Can Early Menopause Prompt Depression Later in Life?

I’m not sure what was worse: the immediate shock of learning I was in premature menopause or the low-grade depression that I slumped into in the weeks afterward. I think I was numb for a day or two, then the reality hit me like a wall. I kept trying to push my emotions aside, telling myself I could handle it, that it wasn’t that bad. But I couldn’t stop the grief about being suddenly infertile, the fears about my health, and all the questions that kept rattling around in my head: Was I still sexy? Was I old? Was I attractive? Was I still a real woman? I didn’t feel like me any more. . .
(The Premature Menopause Book, by Kathryn Petras)


Early menopause and POF bring with it a wrenching emotional change along with the physical one. Yes, your emotions are inevitably affected by the shifting hormones in your body. And the reality of your condition affects your emotions even more. Not surprisingly, a recent, study conducted in London found that premature menopause was substantially associated with higher than average levels of depression. The single most upsetting element of premature menopause, according to all the women surveyed, was the most basic: Their loss of reproductive capacity. It did not make a difference if they had children or not -- or even if they had been trying to have children. The sudden switch from fertile woman to irrevocably infertile woman was the biggest blow of all.

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Other studies also revealed the causal relationship between premature menopause and chance of clinical depression later in life.

The risk for postmenopausal depression is decreased with later age at menopause, supporting evidence of potential anti-depressive effects associated with longer exposure to endogenous estrogens, latest meta-analysis suggests.

"Our analysis showed that overall, increasing age at menopause by 2 years decreases the postmenopausal risk by 2% (per 2-year increment)," admitted lead author Eleni Th Petridou, MD, PhD, of the National and Kapodistrian University of Athens, in Greece.

"Considering that age at menopause may differ among women up to 20 years, the cumulative protective effect becomes quite sizeable."

The meta-analysis included 14 studies involving 67,714 women; results showed that increasing age at menopause was linked with a reduction in the odds ratio for depression per 2-year increment. Similar reductions were seen with a longer duration of the reproductive period.

In looking at three studies involving severe depression, which included 52,736 participants, the effect was greater: there was a 5% decrease in the risk for severe depression with each 2-year increase in age at menopause. Three studies that controlled for past depression also showed decreases in subsequent depression with older age at menopause.

Four studies, involving 3033 participants, showed that menopause at age 40 years or later was associated with a 50% decreased risk for depression compared with menopause occurring in women younger than 40 years.

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Studies that included women with surgically induced menopause were not included in the meta-analysis, but the authors said the findings were "in accordance with previous studies reporting that early menopause due to oophorectomy increases the risk of depression later in life."

Importantly, the association of increased postmenopausal depression with earlier menopause remained consistent after controlling for use of hormone replacement therapy (HRT) ― in the seven studies (56,813 cases) in the analysis that included HRT data, the proportion of patients having ever received HRT varied between 20% and 45%. There were no significant differences in the results in those patients.

"It seems that HRT use does not offset the odds of depression," Dr Petridou said. "It should be noted, however, that other endogenous sex hormones, such as progesterone, might also be implicated in the protection conferred against postmenopausal depression."

The findings appear to underscore a neuroprotective role of circulating estradiol, which some studies have shown "acts in neurons and glial cells via the intracellular estrogen receptors α and β, as well as [having] antiatherogenic actions including enhancement of endothelial function, blockage of smooth muscle cell proliferation, and inhibition of inflammation," the authors write.

In terms of prevention of the potential loss of those benefits, as a result of early menopause, clinicians should monitor those patients, and research should continue to focus on refining HRT, Dr Petridou said.

"The findings of the current meta-analysis point to women with a premature menopause as a high-risk group for selective depression screening and close mental follow-up to identify depressive symptomatology earlier and treat it more effectively," Dr Petridou said.

Furthermore, randomized, controlled studies should be aimed at preventing postmenopausal depression with new and targeted sex HRTs, she added.

"The significant differences of exogenously administered sex hormones should be seriously considered in new studies to come up with safer HRT conferring also anti-depressive protection of endogenous sex hormones."

In an editorial, that accompanied the study, Hadine Joffe, MD, director of the Division of Women's Health, Brigham and Women's Hospital, in Boston, Massachusetts, and Joyce T. Bromberger, PhD, of the University of Pittsburgh, note, that early menopause has been already associated in previous researches with a variety of non-psychiatric diseases, including cardiovascular disease, cognitive decline, and dementia, and that the new analysis underscores the risk for depression.

"The current article adds postmenopausal depression to that list, with findings that show similarly that the effect of a slightly early natural menopause is small, while the effect of premature menopause is much stronger," they say.

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