MENOPAUSE EFFECTS ON THE AGING FEMALE

MORE REASONS TO JUSTIFY HORMONE REPLACEMENT

Vasomotor symptoms may begin up to 7 years before the final menses and may last 7 years after the final menses. VMS become the “canary in the coal mine” signaling estrogen production has begun to fluctuate. In a study by Suzuki with mice, they concluded that estradiol protected the brain tissue by suppressing the inflammation through ER alpha mediated mechanisms. Estradiol down regulates the expression of proinflammatory cytokines, including interleukin (IL)-6, monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha. (3)

Concerning stroke and the neuroprotective effects of estrogen, Dubal and Wise have stated “women may now live over three decades of their lives in a hypoestrogenic, postmenopausal state. The impact of prolonged hypoestrogenicity is now a critical health concern. Conversely replacement with estrogen appears to act in the primary prevention of many disease processes, including neuro-degeneration.” Furthermore, Dubal and Wise postulated that pharmacologic levels of estradiol protect through mechanisms that do not require estrogen receptors, whereas physiological levels of estradiol protect the brain through mechanisms that depend on estrogen receptors. (3)

Women 90 years and older in the United States has increased dramatically in the past century. Currently estimated at 1.3 million, which is expected to quadruple by 2050. Cardiovascular mortality risk is reduced if a woman begins her period later and enters menopause later. Midlife, typically defined as age 40-65 years is a critical time for women. Midlife is a time of pronounced changes in the body composition, cardiometabolic health, mood, sleep, cognition, and overall functioning and is a period in the lifespan directly preceding a heightened risk of major chronic diseases, such as cardiovascular disease (CVD). The last 25 years, has brought critical insights from the studies designed to look at women from premenopausal years through menopause, including the Study of the Women’s Health Across the Nation (SWAN), the Seattle Women’s Health Study, The Melbourne Women’s Midlife Health Project, The Healthy Woman Study, and the Penn Ovarian Aging Study (POAS). (1)

CVD is the leading cause of death among women, accounting for a third of all female deaths. The incidence of coronary heart disease (CHD) in women lag behind that of men by almost a decade, wtih CHD events occurring primarily when women are postmenopausal. The menopause transition has been viewed as a time of accelerating CVD risk. However, whether increases in CVD in the postmenopause are due to menopause or to chronological aging remains debated.

SWAN provides some of the strongest evidence on menopause related changes in lipids showing that total cholesterol, low density lipoprotein cholesterol (LDL-C) and apolipoprotein B levels increase markedly within the period from the year before to the year after the final menstrual period, independent of aging alone. (2)

Historically, Wilson and Wilson advocated estrogen forever to keep women young and vibrant. Subsequently, estrogen was promoted to decrease osteoporosis and heart disease . Currently, the US Food and Drug Administration (FDA) recommendations are to treat only vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM) and possibly to prevent progression of osteopenia to osteoporosis with the lowest dose for the shortest duration of time. We question whether it is “normal” for these ubiquitous receptors to perform suboptimally in the postreproductive phase of a woman’s life and ignore all of the other putative benefits of estrogen. If menopause is physiological and a natural concomitant of aging as espoused by many, then why do we treat hypo-estrogenemic conditions such as VMS, GSM, and osteoporosis? (3)

Estrogen prevents cell death by maintaining functionally intact mitochondria. It is important to replace during perimenopause before we become estrogen depleted due to the fact that once our mitochondria is senescent it is too late and shows no benefits in restoring. Brintons laboratory corroborates that mitochondria burn glucose over alternative fuels (ketones) 100:1 in the presence of normal estrogen in young controls. In the case of patients with Alzheimer’s disease the ratio of glucose to ketones is 2:1 and after menopause and not on hormone therapy mitochondria use ketones, the breakdown product of which is beta amyloid.

The Eye Disease Case Control Study Group at the National Eye institute showed decreased risk of age related (wet) macular dgeneration with postmenopausal exogenous estrogen use. The Beaver Dam Eye Study, a prevelance survey study of eye related disease in a community, found a modest protective effect of long term estrogen use on lens opacities with atleast 5 years use and the greatest benefit with 20 years of postmenopausal hormone use. (3)

Skin turgor and capillary blood flow velocity are significantly decreased in menopause, but are reversible with hormone therapy. Spangenberg et al found that exogenous estradiol replacement corrects lipolytic dysregulation that is not achieved with exercise and stated “estrogens encourage physiological mechanisms that prevent chronic disease” Estrogen appears protective in metabolic dysfunction and can even reverse it. Estrogen also appears to be protective in nonalcoholic fatty liver disease. Conversely, reduced circulating estrogens result in adipocyte hypertrophy and change in lipid metabolism in the liver. These metabolic changes, including increased visceral fat, are consistent with findings in Clarkson et als stressed monkeys

Killicdag et al evaluated hearing in postmenopausal women and in the group using estradiol found better low frequency air conductance hearing and the authors proposed estrogen replacement maintain ion and fluid balance of the inner ear, which is impaired in the postmenopausal period. Paganini-Hill evaluated the Leisure World Cohort for oral health. The risk of tooth loss decreased with increasing duration of estrogen therapy and estrogen users and an inverse relationship was reported between estrogen use and tooth loss. The authors postulate estrogen’s anti inflammatory properties in reducing gingivitis and estrogen’s impact on mandibular bone and osteoporosis. (3)

Age at menarche and natural menopause and number of reproductive years in association with mortality: results from a median follow-up of 11.2 years among 31,955 naturally menopausal Chinese women Wu X1, Cai H1, Kallianpur A1, Gao YT2, Yang G1, Chow WH3, Li HL2, Zheng W1, Shu XO1.

Menopause versus chronologic aging their roles in women's health

Thurston, Rebecca C. PhD; Karvonen-Gutierrez, Carrie A. PhD, MPH; Derby, Carol A. PhD; El Khoudary, Samar R. PhD, MPH; Kravitz, Howard M. DO, MPH; Manson, JoAnn E. MD, DrPH, NCMP Menopause: August 2018 - Volume 25 - Issue 8 - p 849–854

A theory of eu-estrogenemia a unifying concept Turner, Ralph J. MD, FACOG, NCMP1; Kerber, Irwin J. MD, FACOG, FACS, NCMP2 Menopause: September 2017 - Volume 24 - Issue 9 - p 1086–1097