Journal of Womens Health, Issues and Care ISSN: 2325-9795

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Short Communication, J Womens Health Issues Care Vol: 5 Issue: 1

A Genetic Need for Menopause: Reflections and New Perspectives

Logan Havemann, Rose Maxwell and Steven R Lindheim*
Department of Obstetrics and Gynecology, Wright State University, Boonshoft School of Medicine, Dayton, Ohio, USA
Corresponding author : Steven R. Lindheim, MD
MMM, 128 Apple Street, Suite 3800 Weber CHE, Dayton, Ohio, USA 45409
Tel: (937) 208-2301; Fax: (937) 222-7255
E-mail: [email protected]
Received: January 28, 2016 Accepted: March 07, 2016 Published: March 12, 2016
Citation: Havemann L, Maxwell R, Lindheim SR (2016) A Genetic Need for Menopause: Reflections and New Perspectives. J Womens Health, Issues Care 5:1. doi:10.4172/2325-9795.1000218

 

Abstract

Tradition has taught women to view menopause as the “beginning of the end”, the beginning of a decline in health, where they will have to handle the effects of illness, disability and dependency. Women have fought the effects of aging and menopause through botox injections, plastic surgery, and use in vitro fertilization and hormone replacement therapy to maintain the ability to reproduce and continue feeling young. Despite these efforts to maintain what we see as “valuable life”, genetic studies have revealed the potential for another purpose to the menopausal period in a woman’s life, the ability to grandparent and the evolutionary advantages of this. In this light, menopause should perhaps not be viewed as the “beginning of the end”, but rather the “end of the beginning”. In a proposed grandparent hypothesis, grandmothers increase the growth of infants by assisting in providing for food for nursing mothers and infants which ultimately accelerates infants’ growth, allowing for them to be weaned sooner, and thus allowing the female to reproduce more. Recent genetic literature suggests that menopause may offer the selection for alleles, specifically the CD33 allele, which may protect against cognitive decline in post-reproductive humans, allowing humans to grandparent. Without these alleles, cognitive decline in the post-reproductive population may decrease the ability of grandparents to provide food and contribute knowledge to their offspring, and deters resources to the care of the aged and demented, thus hindering their grandchildren’s reproductive success. This suggests that there is a genetic need for menopause, and serves as an opportunity to reflect on the evolution of thought from reversing menopause to viewing it as another important stage of a woman’s life, which genetics may have selected for in order to sustain the continuation of our species.

Keywords: Menopause; Genetic need; Hormone replacement therapy

Keywords

Menopause; Genetic need; Hormone replacement therapy

Introduction

We are always striving to try to turn back the time, wishing for yesterday. From botox injections, to dying the grey hair, to my personal trainer session, if I could find the fountain of youth I’d be the first in line. As a woman and professional who considers myself to still be in my prime, 56 years young to be exact, I spend a great deal of time pondering the aging process of menopause.
Menopause is no stranger to womankind; the menstrual irregularities, periodic hot flashes and night sweats, not to mention the irritability and change in sex drive that comes with it, is something we’re all taught to fear from the time we were little girls watching our grandmothers go through “the change”. I, like many, used hormone replacement therapy to help prevent the physical changes that come with dropping levels of estrogen, I went through plastic surgery and I underwent in vitro fertilization, with an egg donor to have my youngest child 7 years ago just trying to overcome mother-time, simply not to age. I will admit that I initially viewed menopause as the beginning of the end, the beginning of the time at which my body would begin to deteriorate and I would no longer be able to have and do the things I used to take for granted.
Since the beginning of time, women have experienced acute issues associated with menopause including hot flashes, night sweats, vaginal dryness, mood swings, and irritability just as I have. We also have had to deal with chronic issues including increased cardiovascular disease, osteoporosis, urinary incontinence, and cancer. All of this was thought to change with the advent of hormone therapy (HT), our first attempt to turn back the clock on menopause.
HT has been around since 1898 when the first preparation, an injectable form, was first being used to treat menopausal symptoms [1]. The first FDA approval for oral HT came almost 50 years later in 1942, consisting on conjugated equine estrogens (CEE), which was branded Premarin for the treatment for hot flashes and other symptoms associated with menopause [2]. By the 1960’s unopposed estrogen was widely used and women everywhere were proclaiming it to be the fountain of youth [3]. In the 1966 book, Feminine Forever, by Robert A. Wilson, M.D., encouraged women undergoing “the change” to take estrogen as “menopause was completely preventable” [4]. Remaining “Feminine Forever” was met with enthusiasm and in the early 1970’s; an estimated 45% of menopausal women were using HT [3].
The HT fever did not last indefinitely. By the mid-1970s, the use of HT starkly declined after studies demonstrated that unopposed estrogen, promoted the growth of uterine tissue and was linked to an increase in endometrial cancer [3,5-8]. By the late 1970’s, the increased cancer risk led to the halving of the number of HT prescriptions in the United States [5]. It did not take researchers long to fix this issue. It become clear that progesterone when combined with estrogen decreased the proliferation of uterine tissue, reducing the risk of endometrial cancer [6]. This reassured many of us regarding its safety and renewed hope for a cure for menopause. The pharmaceutical and medical communities rallied behind this new idea of a “combinationpill”, and Prempro, an oral combination of a synthetic progesterone named progestin and the CEEs was born [3,5]. By the end of the 1980’s, flocks of women were using combined HTs, and this time at rates exceeding those of the pre-1975 era [3,5,7]. Combination HT usage continued to steadily increase throughout the 1990’s [5], and doctors were strongly promoting its usage when Prempro then received FDA approval in 1995 for not only treatment of moderate to severe vasomotor symptoms associated with menopause, but also for the prevention of osteoporosis in women at risk [9].
Prior to the 1990s, there were observational studies that suggested that HT, particularly estrogen, was cardio-protective [3,5,7,8]. Given there were limited randomized controlled trials that examined the long-term effects of HT, there was a push to clearly establish causality that lead to the landmark Women’s Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS) randomized clinical trials to test if HT could be used for primary and secondary cardiovascular disease prevention and protect against conditions of aging. However, in 2002 when the results of the WHI came out, the landscape of HT use again was changed forever. The results showed that daily combined estrogen-plus-progestin were associated with increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis, while the estrogen-alone arm of the WHI reported increased risks of stroke and deep vein thrombosis [10]. Furthermore, the Women’s Health Initiative Memory Study, a sub study of WHI, reported an increased risk of developing dementia in postmenopausal women 65 years of age or older with combined estrogen-progestin and with estrogen-alone [10]. More recent data suggests that while HT in older postmenopausal women is not indicated for primary and secondary disease prevention, there may be benefits in younger new onset postmenopausal status [11]. An understanding continues to evolve regarding HT use, though the fountain of youth may need to be sought elsewhere.
With respect to motherhood, in the 1980’s, Drs. Trounson [12] and Sauer [13] forever changed the landscape of the traditional family unit. In today’s age, we are seeing a staggering number of women pursuing careers and focusing on personal goals before settling down to have a family. Like many other women, by the time I was ready to have a family, my biological clock was expiring and I was knocking on menopause’s door and I was told I would struggle to conceive. However, with the help of donor eggs I could cheat out my infertility. Essentially, women who were once “too old” to bear children could now start and finish having the families at any age.
However, there appears to be a price as we roll the dice using donor eggs. Since the first pregnancy in July 1983 was announced from IVF using a donor egg, an estimated over 47,000 live births have occurred since as a result of IVF with donor eggs in the United States [14]. However, results suggest that using donor eggs in postmenopausal women such as I have increased risk of obstetric and neonatal complications compared to younger women with POF included pre-term labor, gestational hypertension, gestational diabetes mellitus, premature rupture of membranes, placental complications and intrauterine growth retardation [15]. While we are granted the opportunity to bear children and parent into our 50’, 60’s, and even our 70’s, there appear to be a significant risks to mother and child, when these times are typically reserved for the title of grandparent(s).
From the medical perspective, we have been working to delay if not prevent the inevitable time of menopause, a period that some have described as the “beginning of the end”. On the other hand, some might say, we might be at the “end of the beginning” and embarking on a new stage of life. In Walker’s Mother Time: Women, Aging, and Ethics, it is explained that it takes a long time to grow old, the point at which our bodies begin to decline, comes years even decades after the onset of menopause. It is important to conceptualize that aging encompasses more than a preoccupation with the illnesses, disability, and dependency that come in the advanced stages of the elder years. As the author states, “Aging is living through the process of physical change, shifting cultural expectations, and social and personal adjustments that later life brings” [16]. We have spent many years of research trying to outsmart mother time. Through HT and IVF, our efforts have focused on trying to preserve what we view as “valuable life”, times when we can feel young again and even reproduce. It has been described that menopause actually marks a new phase in our lives where we have the opportunity to take on a different role, one that is not afforded to every species, which is the ability to grandparent. The irony is that our attempts to prolong what we viewed as valuable life, the time before the “beginning of the end” are not exactly novel, as genetics has been feeding into this opportunity to grandparent long before we ever tried.
In all known vertebrae, the typical lifespan extends to shortly after reproduction ceases except in orcas, pilot whales and humans [17]. This is based on the premise that natural selection favors genetic variations that increase survival, fertility, and reproductive success. In these 3 distinct species, lifespan is prolonged into the post reproductive phase and allows for elder group members to contribute to the reproductive success of younger generations. There is evidence that in many primate-species, mother-child food sharing occurs in which mothers substantially supplement their weanedchildren’s foraged diets with the surplus of their own foraged food. It has been hypothesized that post reproductive females who assist in providing food for their fertile children and grandchildren produce more offspring than those who continue to have complicated lateage pregnancies and are likely to produce offspring that will not survive their death. It is from this that the “grandmother hypothesis” was derived by Hawkes and others. They suggest that women have an increased post reproductive lifespan in order to grandparent. As grandmothers, they increase the growth of infants by assisting in providing for food for nursing mothers and infants which ultimately accelerates the growth of infants and allows for them to be weaned sooner, allowing the female to reproduce more [17].
Recent literature and genetic evidence actually suggests that menopause may offer distinct advantages to the survival and continuation of our species through selection for alleles that may protect against cognitive decline in post reproductive humans, allowing humans to grandparent. As post menopause is not a time of fertility and reproduction, natural selection for genes that have benefits during this time is weak. However, it has been hypothesized by Schwarz et al., that cognitive decline in the post reproductive population decreases the ability of grandparents to provide food and contribute knowledge to their children and grandchildren, and deters resources to the care of the aged and demented, thus hindering their children’s reproductive success [16]. It is thus reasonable to suggest that there may be a selective force for genetic variants to protect against cognitive decline.
In 2015, Schwarz et al. examined the contributions of CD33, an immune regulatory receptor, to Alzheimer’s dementia [18]. Their results showed that despite the weak influences of natural selection at advanced age, there exists a CD33 allele that is protective against the development of Alzheimer’s dementia, by suppressing amyloidbeta peptide accumulation in the brain [16]. One of human’s closest living evolutionary relatives, the chimpanzee, does not demonstrate Alzheimer’s development. Using genomic analysis of non-human primates, they first confirmed that the protective CD33 allele is derived in humans, and does not exist in any of our primate ancestors. This serves to suggest that through natural selection humans have evidenced adaptation to the cognitive decline associated with aging. Although this protective allele is only found at an overall frequency of 0.21 in the human population, it serves to suggest that through natural selection there may be a benefit and protective factor associated with menopause.
What all this may suggest is that menopause may not be the “beginning of the end”, a time where female health starts a rapid decline, but rather an “end to the beginning”, where women take on a grandparent role to help to procure the survival and reproduction of their descendants. While menopause is a period that physicians are devoted to reversing through HT and egg donation, it is also an opportunity to open the eyes of women and medical professionals to see this as another important stage of life, grand parenting, as genetics may have selected for. The medical community has devoted a great deal of research into delaying natural menopause and its complications, when in fact, may be necessary in our natural selection process as a species.

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