Women’s Healthspan: Why The Story Starts Before Menopause
Women’s healthspan, the number of years lived in good health, is shaped by more than the years around menopause. The ovary is among the first organs to show signs of ageing.
A 2025 review in MedComm places the start of a noticeable fertility decline in the late 20s and its acceleration after age 35, with menopause at around 51. Jennifer L. Garrison, writing in PLOS Biology in 2026, reports that signs of ovarian ageing can be detected in women’s twenties and thirties, and that by the time menopause makes the process visible, it has been running for two to three decades.
The ovary was filed under reproduction
For most of the past century, ovaries were classified solely as reproductive organs. Garrison argues that this label routed ovarian biology through gynaecology and reproductive medicine, specialties built around fertility and its clinical management. Fertility occupies a window of roughly 30 years, while ovarian ageing shapes health across the whole of life.
She describes the ovaries as holding a two-way exchange with most tissues in the body through hormones and other circulating molecules, an exchange that changes profoundly as they age. Over the following decades, the consequences reach the brain, heart, liver, blood vessels, immune system, bone, skin and muscle. Her central claim is that ovarian ageing is a primary determinant of healthspan.
PLOS Biology describes the Perspective format as a forum for experts to comment on topical or controversial issues. It is an argued position, not a new trial.
Ovarian ageing starts before menopause
Garrison treats menopause as closer to the end of ovarian ageing than the beginning, and argues that organising research around menopause as the main exposure is a mistake.
The follicle counts fit that timeline. A 2010 PLOS One model by Hamish Wallace and Thomas Kelsey estimated that for 95% of women, only 12% of the maximum pre-birth follicle population remains by age 30, and only 3% by age 40. The estimate rests on cross-sectional counts from earlier histology studies, many of them from surgical samples in older women, and on an assumption the authors call suggestive but not conclusive. These are estimates of the egg supply. They do not describe hormone levels or how any one woman feels. Garrison says the field still needs to discover why the timing of ovarian decline varies so widely between women.
What research links to ovarian decline
A 2025 review in MedComm by Xingyu Liu and colleagues at Tongji Hospital in Wuhan reports that declining ovarian function contributes to age-related disorders including osteoporosis, neurodegenerative diseases and cardiovascular conditions. The authors tie this to the fall in oestrogen after menopause and to oestrogen receptors being spread across many tissues.
They also point to mechanisms beyond oestrogen. Ageing ovarian cells release inflammatory molecules that may enter the circulation and drive chronic low-grade inflammation. The review also notes that falling levels of anti-Müllerian hormone, a marker of ovarian reserve, have been linked in emerging clinical studies to higher cardiovascular risk and insulin resistance. It examines possible links with conditions it classes as potentially age-related: type 2 diabetes, fatty liver disease, chronic kidney disease and chronic obstructive pulmonary disease.
The authors propose that ovarian ageing may act as a catalyst for age-related diseases in women. They also say more high-quality clinical data are needed to strengthen the evidence linking ovarian ageing to Alzheimer’s disease.
In a separate 2026 PLOS Biology essay, Priscila Chiavellini and Vittorio Sebastiano note that women spend a third or more of their lives in the post-reproductive state. They write that if ovarian decline contributes causally to cardiovascular, metabolic, cognitive and skeletal ageing, then extending ovarian healthspan is a systemic matter and not a reproductive one. The “if” matters. The essay is open about its limits: the supporting evidence comes mostly from rodent studies, and the authors say it does not yet show that the ovary actively directs a systemic rejuvenation programme. For now, they describe the ovary as a node that the rest of the body depends on.
What happens when ovarian function is lost early
The clearest evidence that ovaries do more than support fertility comes from women who lose ovarian function early. Garrison points to premature menopause, primary ovarian insufficiency and surgical removal of the ovaries, each linked to substantially higher risks of cardiovascular disease, cognitive decline, osteoporosis and metabolic dysfunction.
Mayo Clinic research led by Walter Rocca, published in JAMA Network Open in November 2021, studied 2,732 women aged 50 to 89 in the Mayo Clinic Study of Aging. Women who had both ovaries removed before menopause and before age 46 had higher odds of mild cognitive impairment (adjusted odds ratio 2.21) and lower scores on global cognition and on attention and executive function, about 30 years after surgery. The pattern did not appear for removal at ages 46 to 49, at 50 and over, or after menopause. Among women operated on before age 50, it appeared when the reason was a benign ovarian condition, but not when it was cancer or when no ovarian condition was present.
The authors say the retrospective, observational design means they cannot draw causal conclusions. They call for replication in a long-term follow-up with repeated cognitive testing, and note that participants were mostly White and lived in one Minnesota county. The study describes what happens when the ovaries are lost early. It does not predict the risk for a woman going through natural menopause.
Why women’s ageing research has gaps
Garrison notes that the large longitudinal cohorts underpinning ageing research were built predominantly on males, with female biology secondary at best and absent most of the time. Most multi-organ ageing clocks leave out the ovary, and ovaries were missing from the original Human Cell Atlas and added only years later. Cohorts that track ovarian ageing alongside systemic health across a woman’s life do not exist.
She writes that how the loss of ovarian signalling spreads across tissues in the decades before menopause is unknown, because no study was designed to find out. She also says age at natural menopause is missing from large clinical trial datasets and should be recorded routinely.
Where menopause management and HRT fit
None of this argues against treating menopause. Garrison states that menopausal hormone therapy is the best available treatment for the health risks that accompany menopause, and that renewed clinical enthusiasm for it is broadly justified. Her concern is that the formulations have changed little since the 1940s, and that the field still needs to learn what sets ovarian ageing in motion and why its timing varies so widely.
The MedComm review is more guarded. It says hormone replacement therapy relieves symptoms of oestrogen deficiency, but that long-term use is associated with potential cancer risks and does not address the fundamental ageing mechanisms. For the cancer point it cites the 2002 Women’s Health Initiative trial of oestrogen plus progestin.
A healthspan view adds questions to menopause care. It does not replace it. Whether hormone therapy suits you depends on your circumstances, and that decision belongs in a conversation with a clinician.
What a consultation at Body Brilliant starts with
Consultations at Body Brilliant start with where you actually are: your cycle history, your family history and, where testing is clinically appropriate, your hormone levels. These are reviewed under the oversight of our CQC-regulated, doctor-led clinical team before any treatment plan is built. The starting point is your own record, not a generic age bracket.
Testing has limits that depend on age. NICE guidance says perimenopause is diagnosed from vasomotor symptoms and irregular periods, without laboratory tests, in otherwise healthy women over 45 with menopausal symptoms. It recommends considering a blood test for follicle-stimulating hormone only in women aged 40 to 45 with symptoms and a change in their cycle, and in women under 40 in whom menopause is suspected.
Frequently asked questions
What is ovarian ageing?
Garrison defines it as the progressive functional deterioration of an organ that signals to the rest of the body through hormones and local messengers, with consequences across the whole body. She separates it from reproductive ageing, which refers to ageing of the ovaries, fallopian tubes and uterus that leads to lower fertility.
When does ovarian ageing start?
Garrison reports that signs can be detected in women in their twenties and thirties. The MedComm review places the start of a noticeable fertility decline in the late 20s. Menopause comes at around 51 on average.
Does ovarian ageing cause osteoporosis or heart disease?
The MedComm review links declining ovarian function to osteoporosis, neurodegenerative diseases and cardiovascular conditions, and its authors propose that ovarian ageing may act as a catalyst for age-related disease in women. They also say more high-quality clinical data are needed for some links, such as Alzheimer’s disease. These are associations and proposals, and causation is still being worked out.
Does thinking about healthspan replace HRT?
No. Garrison calls menopausal hormone therapy the best available treatment for the health risks that accompany menopause. The MedComm review notes potential cancer risks with long-term use. Whether it suits you is a decision to make with a clinician.
What’s something about your own health that changed faster than you expected it to?
Book a private consultation: here
This article is general information and is not medical advice.
Sources
Garrison JL. Beyond reproduction: The ovary as a systemic regulator of female health and aging. PLoS Biol. 2026;24(5):e3003800. doi:10.1371/journal.pbio.3003800
Chiavellini P, Sebastiano V. From germline immortality to somatic rejuvenation: Unlocking the ovarian blueprint for longevity. PLoS Biol. 2026;24(5):e3003804. doi:10.1371/journal.pbio.3003804
Liu X, Zhao Y, Feng Y, Wang S, Zhang J. Ovarian aging: mechanisms, age-related disorders, and therapeutic interventions. MedComm. 2025;6(12):e70481. doi:10.1002/mco2.70481
Rocca WA, Lohse CM, Smith CY, Fields JA, Machulda MM, Mielke MM. Association of premenopausal bilateral oophorectomy with cognitive performance and risk of mild cognitive impairment. JAMA Netw Open. 2021;4(11):e2131448. doi:10.1001/jamanetworkopen.2021.31448
Wallace WHB, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One. 2010;5(1):e8772. doi:10.1371/journal.pone.0008772
NICE. Menopause: identification and management (NG23), recommendations 1.2. nice.org.uk/guidance/ng23
Cited by MedComm for the HRT cancer point: Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
