Menopause and Reproductive Longevity in women’s health: What science tells us
How menopause, reproductive health, and ovarian aging are interconnected in women’s longevity.
At Maximon, we are on a mission to constantly deliver the latest scientific advancements in Longevity and Aging. We carefully read and select the most relevant and impactful scientific publications to keep you informed about the rapidly evolving developments in this field. In the present article, we are exploring what menopause is, how it can impact women's health and how women's reproductive status is strictly linked to their longevity.
Menopause leads to a decline in hormone production and has negative effects on women’s health
Menopause is defined as the cessation of menstrual periods for at least 12 consecutive months and typically occurs in women between the ages of 45 and 55, although it can happen earlier or later. During menopause, a woman's ovaries stop releasing eggs, leading to a decline in the production of hormones like estrogen and progesterone.
This significant hormonal shift is accompanied by a variety of physical and emotional changes, which underlie many menopausal symptoms and health effects, including hot flashes, night sweats, mood swings, vaginal dryness, bone and heart health changes.
Understanding how reproductive hormone levels change is crucial for elucidating the body changes, and consequently the symptoms, women experience during menopause.
The most notable hormonal change is a substantial decrease in estrogen levels, typically averaging around an 80% reduction during the first year of menopause. Estrogens, in addition to their central role in reproductive system development and menstrual cycle regulation, have significant effects on various aspects of women’s health. These effects include preventing bone loss, promoting cardiovascular and neuronal health, and mitigating inflammation.
Moreover, estrogen has been linked to molecular mechanisms that regulate the biological aging process and the hallmarks of aging.
Reproductive lifespan is strictly associated with healthspan and longevity
Longevity in women has been found to be associated with several reproductive factors, pointing out a strong relationship between chronological life span, reproductive lifespan and health.
In recent years, there has been a growing focus on ovarian aging, which is defined as a natural and gradual reduction in both the quality and quantity of eggs (oocytes), ultimately leading to infertility and the onset of menopause. What makes it particularly intriguing is that ovaries are the first organs in the female body to age. Therefore, ovarian aging plays a central role in influencing the aging of various other organs throughout the female body, serving as a sort of catalyst for their aging processes.
Women possess all the oocytes they will ever have from birth, and the total number of viable oocytes is defined as “ovarian reserve”. At the onset of a woman’s fertility, the ovarian reserve decreases by 65-75%, with the quantity and quality of oocytes varying widely between individuals.
Ovarian aging is significant for two key reasons. Firstly, its link to menopause and the associated decline in estrogen is linked to a decline in women's overall health, potentially leading to an extended period of poor health during their lifespan (despite women living on average longer than men). Secondly, ovarian aging exerts pressure on women to consider reproduction before they reach the average age of infertility.
Furthermore, an intriguing discovery reveals that the age at which women experience menopause strongly correlates with their lifespan. Women who enter menopause at a later age tend to live longer, while those who experience early menopause face higher risks of morbidity. While the exact reasons behind this phenomenon remain unclear, gaining insights into what influences ovarian aging can provide valuable insights into the aging process of the entire body, and delaying menopause could mean extending the reproductive years and presumably lifespan as well.
Where does Science stands?
Delaying ovarian decline could potentially delay the onset of diseases that are associated with a decline in estrogen production and menopause onset, such as increased risk of developing osteoporosis and cardiovascular events.
What are the therapeutic possibilities to potentially target ovarian fitness and delay ovarian aging? Ongoing research is exploring various approaches to promote ovarian longevity:
Dietary Supplements: Researchers are investigating the potential of supplements and antioxidants to support ovarian health. Studies have shown that the accumulation of reactive oxygen species (ROS) can impact oocyte quality by promoting apoptosis, inflammation, telomere shortening, and mitochondrial damage. Among the antioxidant therapies, melatonin, vitamins (C & E), resveratrol, quercetin, and curcumin are gaining attention.
NAD+ precursors: Mitochondrial dysfunction is considered one of the hallmarks of aging and can adversely affect oocyte health. As a result, extensive research is concentrated on rejuvenating mitochondria by increasing NAD+ levels, a molecule responsible for generating energy in cells. Although further research is needed, NAD+ boosters currently investigated are NR and NMN.
Caloric restriction mimetics: Various studies have demonstrated that caloric restriction (CR) has different effects on rodents and humans. While it appears to be beneficial in animal models, it does not hold the same magnitude of effects in humans. Moreover, implementing CR in real life practice can be challenging. Therefore, researchers are investigating possible CR mimetics that act on the same signalling pathways, such as metformin, rapamycin and resveratrol.
Hormone Replacement Therapy: Hormone replacement therapy (HRT) aims at alleviating the symptoms of menopause by supplementing the body with estrogen and progesterone. The eligibility for HRT treatment is generally individualised, typically considered for women within 10 years of menopause onset and without specific risk factors like breast cancer. While HRT doesn't directly delay ovarian aging, it can help prevent cardiovascular disease, osteoporosis, and cognitive decline.
While there are still open questions about the causes of ovarian aging, these approaches hold significant potential for prevention rather than just symptom treatment.
Current and future challenges
Menopause is often seen as a natural part of life, where the ovaries stop working. However, as a result of advancements in research and healthcare, it is becoming more and more clear the importance of recognising menopause as a relatively recent development. Today, women can live beyond 80 years on average. Given that menopause typically occurs around age 50, it means women are living for many years without their ovaries performing their vital functions. This highlights the significance of looking at menopause as a notable public health issue, marking a stage in which a crucial organ - ovaries - experiences a decline in its function.
Pharmacological treatments hold promise for addressing age-related health issues and frailty. Unfortunately, the lack of information on how longevity treatments specifically affect women's health and lifespan still creates a significant knowledge gap. A 2023 systematic review revealed that 40% of the studies that successfully tested compounds to promote healthspan exclusively used male mice or didn't specify the mice's sex. Therefore, we stress the importance of including both men and women in research studies to gain valuable insights into the aging process and improve healthy aging for everyone. Only by considering sex differences can we uncover new knowledge about how aging functions.
The field of reproductive longevity still needs to be built up but, at the same time, it holds an enormous potential to advance our knowledge. In 2019, the Buck Institute inaugurated the Global Consortium for Reproductive Longevity & Equality (GCRLE), making it the first institution with a specific focus on female reproductive aging and thereby advancing the field of reproductive longevity science. The goal is to incorporate an increasing number of studies that concentrate solely on women when developing geroprotectors and to promote funding for research centred around women's health.
While many challenges remain, there is a growing and emerging interest in ovarian aging research, which brings together efforts from academia, industry, and non-governmental organisations, promising exciting future developments.
It’s Time to Focus on Reproductive Longevity Research. Jennifer Garrison, Wired (2023)
The Secrets of Aging Are Hidden in Your Ovaries. Emily Mullin, Wired (2023)
Ovarian Longevity . Jennifer Garrison, Longevity.Technology (2021)
Recognizing the importance of ovarian aging research. Nat Aging (2022)
Potential Mechanisms of Age Acceleration Caused by Estrogen Deprivation: Do Endocrine Therapies Carry the Same Risks? Sehl & Ganz, JNCI Cancer Spectrum (2018)
Ages at Menarche and Menopause and Reproductive Lifespan As Predictors of Exceptional Longevity in Women: The Women's Health Initiative. Shadyab et al., Menopause (2017)
The Influence of Female Reproductive Factors on Longevity: A Systematized Narrative Review of Epidemiological Studies. Costanian et al., Gerontology and Geriatric Medicine (2022)
Estrogen and Mechanisms of Vascular Protection. Xing et al, Arteriosclerosis, Thrombosis, and Vascular Biology. (2009)
The regulatory landscapes of human ovarian ageing. Jin et al., bioRxiv (2022).
The role of oxidative stress in ovarian aging: a review. Yan et al., J Ovarian Res (2022)
Can ovarian aging be delayed by pharmacological strategies? Zhang et al., Aging (2019)
Sex differences in pharmacological interventions and their effects on lifespan and healthspan outcomes: a systematic review. Knufinke et al., Front. Aging (2023).