Intended for healthcare professionals

Feature Gynaecology

Experimental treatments risk further medicalisation of menopause

BMJ 2021; 373 doi: (Published 11 May 2021) Cite this as: BMJ 2021;373:n992
  1. Sally Howard, journalist
  1. London
  1. sal{at}

Many women experience debilitating menopause symptoms. Fledgling interventions aimed at delaying menopause or treating symptoms are attracting commercial interest, but robust evidence of potential benefit and harms for patients is lacking. Sally Howard reports

Ovarian tissue cryopreservation and transplantation (OTCT)—surgical procedures successfully used to restart ovarian function in young women who have undergone chemotherapy1—are being offered to healthy women in the United Kingdom with a view to reinstate their pre-menopausal endocrine function. But robust evidence of effectiveness and safety in this indication is lacking, and some experts see this as overmedicalisation of menopause.

The private Birmingham based clinic Profam charges healthy women between £7000 and £11 000 (€8000-€12 500; $9500-$15 000) for OTCT. Before menopause, a slice of oocyte rich ovary is laparoscopically resected, cryopreserved, and then regrafted into the pelvis or subcutaneously in the forearm after menopause.

Meanwhile, patients in Canada are being advertised a proposed surgical treatment for early menopause that would involve transferring newly recognised germline stem cells from the ovarian lining to the ovary despite limited knowledge of their development into new oocytes.2 Fertility CARE: The IVF Center, a clinic based in Florida, US, markets the treatment OvaPrime as a “means of stopping your biological clock,” which is “on the cusp of being approved for mainstream use just over the northern border.”3

“We’re seeing something like the commercial big bang that happened with IVF in the 1990s,” says Evelyn Telfer, a biologist at the University of Edinburgh who researches the clinical potential of germline oocyte precursor cells. Private IVF clinics have proliferated since the 1990s, and some now sell a plethora of non-evidence based add-on interventions. “This risks what we saw with IVF—patients paying a lot of money for treatments not ready to be rolled out,” she says.

ProFam’s cofounder Simon Fishel, an IVF scientist, argues that pharmaceutical menopausal hormone therapy, known as hormone replacement therapy (HRT; box 1) has its risks, but proponents should support OTCT as an individualised and physiological form of HRT to tackle what he terms the “hypoestrogenic state” of menopause. “HRT is not the perfect answer for all [women] who want or need it, but it is for many. This is about providing the option of an alternative.”

Box 1

A brief history of HRT

Around 17% of women aged 40 to 69 have taken hormone replacement therapy (HRT),4 and 10 000 prescriptions are issued a day in the UK, according to the NHS. The average British woman will spend 40% of her life post-menopausal.

In the West, menopause typically starts between ages 45 and 55. Around 85% of women experience symptoms, including hot flushes and night sweats, genital symptoms (vaginal dryness and dyspareunia), depressive and sleep disorders, sexual dysfunction, declines in cognitive and cardiovascular function, muscle and joint pain, and osteopenia.5 For one in three people, vasomotor or vaginal symptoms are severe.67

Prescriptions of oestrogen and progestogen, or only oestrogen for women who have undergone hysterectomy, took off in the early 1980s, after the publication in 1966 of the book Feminine Forever by the New York gynaecologist Robert A Wilson. Wilson defined symptoms associated with the onset of menopause as “oestrogen deficiency disease” that could be treated with oestrogen replacement therapy.8

Uptake of HRT has rebounded since the 2000s, when a study showing increased risks of breast cancer, heart attack, and stroke9 caused uptake to halve.10 The debate about breast cancer risk is ongoing, with a recent paper noting that the timing and type of HRT influences breast cancer risk.1112 Current NICE guidelines cover long term benefits and risks.13


Mark P Trolice, IVF specialist and director of Fertility CARE: The IVF Center, told The BMJ, “The field of reproductive medicine has rapidly developed and applied new technology that has not always been thoroughly proven to be effective or even definitively safe for the offspring. However, our obligation is to provide only evidence based medicine and primum non nocere [first do no harm].”

Medicine meets the market

Commercial interest in menopause could feed into the popular narrative that it is a curable disease that all women experience, Telfer says. “Of course we should welcome new treatments for debilitating menopausal symptoms. But we shouldn’t forget that menopause is a natural process.”

Treatment for menopause is “a classic example of overmedicalisation,” says Ray Moynihan, an academic who researches medical overdiagnosis. “You have an utterly natural process that affects half of the world’s population that’s turned into a medical condition that needs treatment,” he says. “This is what we tend to see when medicine meets the market: a drive to treat the biggest populations—populations that are healthy rather than sick. With menopause, this began in earnest with the development of HRT.” Ovarian tissue transplantation, Moynihan adds, “smells of marketing.

“As with all areas of overmedicalisation, GP gatekeepers are key,” he says. “GPs need to be informed of what is being marketed to patients by the commercial sector and help women negotiate the risks and benefits of treatments that are being targeted at healthy people.”

The many women who have troublesome symptoms warrant treatments shown to be effective and safe, which might include hypnosis and cognitive behavioural therapy as well as HRT.14 Toni Hazell, a GP in Tottenham, London, often has discussions with women who are concerned about the breast cancer risk with HRT. “When you look at the actual figures, most women are reassured that the risk is tiny compared with many other risks that we take in day to day life,” she says. “HRT is very safe, particularly when prescribed topically, so most women should be able to find help at their GP. There are a lot of safe private providers out there, but also some unproven treatments offered, and I worry when my patients access these”

The hegemony of HRT

Potential new treatments are being heralded as the beginning of the end of the decades long hegemony of HRT. A fifth of women stop HRT because of side effects or worries about increased breast cancer risk,15 and new non-hormonal treatments might offer hope too to women at increased risk of breast cancer for whom HRT is not recommended.16

A 2006 meta-analysis of studies of OTCT, not for menopause but for fertility restoration in younger women after chemotherapy, found up to 90% of hormone function was restored in an average of 19 weeks, and grafts lasted nine years on average. But OTCT for menopause lacks robust evidence and, as with egg banking, must be started well before the onset of menopause to be of benefit. It is not known how long reimplanted tissue might function for and whether menopause symptoms would merely be deferred.

Melanie Davies, who leads the menopause service at University College London Hospital, says of OTCT for menopause, “Too little is known about the effect on older, otherwise healthy women. Taking enough tissue may even carry the risk of earlier menopause. Laparoscopy also carries [surgical] risk.”

The lure of treatments to reverse menopause may be driven by fear of ageing, she says: “These fears are easy to manipulate for commercial gain.”

Nature sells

A burgeoning market in “natural” herbal remedies and “bioidentical” hormones from plant sources of unknown efficacy and safety is already targeting menopausal women.17 These unregulated products are available online and might lack an evidence base; the concentrations of hormones they contain vary widely.

“There’s a big misconception around what people call ‘bioidenticals,’” says Heather Currie, associate specialist gynaecologist at NHS Dumfries and Galloway and trustee and past chair of the British Menopause Society. “Often they are marketed as preparations made up in special compounding pharmacies that are only prescribed by private clinics. It’s suggested that they are somehow more natural and appropriate than standardised HRT, when in fact standard HRT contains hormones that are very similar to our own, and most importantly they are regulated for safety.”

Other commercial products marketed as “natural” remedies for menopause symptoms include supplements containing ingredients as diverse as B vitamins, wild yam, sage, and St John’s Wort, which make various unsupported claims, including relief of insomnia, anxiety, low mood, and hot flushes.

Naturalness is also used to market OTCT for menopause as well as potential interventions involving germline stem cells, with claims that they could replicate the nuanced fluctuations of a premenopausal woman’s cycle better than doses of synthetic hormone in HRT.

As well as surgical risks in these procedures, OTCT and germline stem cell transfer could mean the return of periods, with obvious downsides. And there are ethical and health implications of women potentially staying fertile for longer, with maternal risks rising exponentially with age.

New drugs trialled for hot flushes

Other treatments prescribed for menopause symptoms include antidepressants, gabapentin, oxybutynin, and clonidine for hot flushes.18 Neurokinin 3 receptor antagonists are non-hormone drugs that are currently in clinical trials to see if they might reduce hot flushes sooner than HRT.19 The drug industry has identified potential returns of €1bn annually from investments in these drugs, which can already be bought online in the United States.

Women with symptoms may one day benefit. But Ray Moynihan, an academic who researches medical overdiagnosis, thinks that neurokinin 3 receptor antagonists “are, like many novel and potentially lucrative treatments, being promoted by people with severe conflicts of interest.”


  • Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

  • Provenance and peer review: Commissioned; externally peer reviewed.


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