How many underserved mass markets remain in healthcare today? Amidst the femtech boom and a heightened focus on women’s health, menopause is finally in the spotlight. However, despite the urgent need for safe and effective alternatives to conventional hormone replacement therapy (HRT)—largely due to the absence of other proven treatment options— and the significant economic impact of menopause, the treatment pipeline still lags behind demand. But why has menopause been ignored for so long? Could it be due to historical perceptions of menopause as a trivial inconvenience rather than a serious health concern? Only 6 menopause drugs were listed in the 2022 PhRMA women’s health category, even though the global population of postmenopausal women is projected to surpass 1 BN by 2025. With total sales of the top 10 menopause products projected to grow from $720 Mn in 2024 to $2.7 BN in 2030 (based on Evaluate Pharma Jul 2024), this highlights the lucrative opportunity for pharmaceutical companies to develop safe, evidence-based treatments to address the unmet need for novel therapies and secure a stake in this expanding market.
Breaking Down Barriers
Despite its significance, menopause has often been overlooked or trivialized in both medical research and societal discourse, resulting in mistaken beliefs, stigma, and inadequate support for women. Up to 90% of postmenopausal women have reported experiencing symptoms during menopause, with approximately half indicating an impact on their quality of life (QoL). However, the majority of women refrain from seeking medical input due to barriers such as a lack of awareness of symptoms, stigma, embarrassment, and misconceptions about ageing. Previous negative experiences in accessing advice or treatment have further hindered women’s willingness to seek help. Moreover, as menopause often occurs during a woman’s peak employment years, it coincides with advancements into higher-level leadership roles. Yet, navigating menopausal symptoms in the workplace presents formidable challenges due to fears of embarrassment and discrimination. The silence around menopause and the absence of workplace support can result in stress, anxiety, reduced productivity, diminished job satisfaction, depression, and, ultimately, women leaving the workforce. But what is being done to address these issues? In a 2023 Chartered Institute of Personnel and Development (CIPD) study involving over 2,000 women aged 40-60 years, which examined their experiences of menopause in the workplace, findings revealed that 17% contemplated leaving their jobs, with 6% ultimately leaving due to insufficient support.
The HRT Controversy
Vasomotor symptoms (VMS), characterized by hot flashes, are the primary menopausal symptom, affecting up to 80% of women with a duration of ~10 years. Beyond discomfort, VMS disrupts sleep, impacts QoL, and triggers fatigue and mood swings, affecting work and relationships. HRT is the go-to treatment for restoring hormone balance during menopause. However, it comes with its own set of risks, including increased chances of breast and endometrial cancer, cardiovascular risks, and blood clots, to name a few. In a 2021 global cross-sectional survey of 3,460 postmenopausal women with menopause-associated VMS, HRT was contraindicated in approximately one in ten. Of those eligible, over half declined HRT, mainly due to the perception that menopause resolves naturally without drug intervention.
The FDA’s approval of Premarin (oestrogen) in 1942 marked the first breakthrough in treating menopausal hot flashes. Surprisingly, it predates the introduction of hormonal birth control by nearly two decades (1960). While numerous birth control options have since been approved, the development of new treatments for menopausal VMS has lagged significantly, owing to a combination of research priorities, regulatory challenges, market dynamics, and the complexity of menopausal symptoms. In 1966, the book ‘Feminine Fever’ thrust HRT into the spotlight, suggesting menopause was preventable by simply supplementing oestrogen, claiming women “will be much more pleasant to live with and will not become dull and unattractive”. This emphasis on conforming to societal expectations of femininity rather than addressing the underlying health issue perpetuates harmful stereotypes by reducing women to mere physical appearance. Nonetheless, this notion, coupled with aggressive marketing efforts by pharma, fuelled a frenzy around HRT, particularly highlighting its supposed benefits for heart health. By 1992, Premarin became the top prescribed drug in the US, with sales surpassing $1 Bn by 1997.
Despite initial hype, calls for longer-term clinical trials arose within the medical community. The Women’s Health Initiative (WHI) conducted the first national randomized clinical study to track HRT in post-menopausal women, comparing the health effects of those who took combined oestrogen-progestin HRT, or, for women without a uterus, oestrogen-only therapy, vs. placebo. In 2002 the WHI reported (1,2) that they pulled the plug on the trial’s oestrogen/progestin arm as the health risks outweighed the benefits due to increased risk of heart disease and a twofold greater chance of developing breast cancer. Evidence from the reanalysis (1,2,3,4,5) of the WHI trial subsequently demonstrated benefit in younger or early postmenopausal women by reducing coronary disease and mortality; however, public opinion of HRT had already been tarnished, with concerns among healthcare professionals (HCPs) and HRT users, many of whom were advised to cease HRT, leading to a notable decline in its usage. With varied views on its benefits and risks and few alternative treatments, many women to this day remain hesitant to start HRT. Consequently, the need to prioritize the development of safe, effective nonhormonal therapies for menopausal VMS relief could not be more evident. Despite the awareness of risks and limitations associated with HRT since 2002, it wasn’t until 2023 that the first nonhormonal treatment for hot flashes was approved. This delay was likely exacerbated by scientific and clinical challenges, including the identification of compounds capable of effectively alleviating menopausal symptoms without hormones, as well as pharmaceutical companies’ reluctance to invest due to perceived regulatory hurdles and market uncertainties.
Nonhormonal Alternatives: A New Era
In 2023, Veozah [US]/Veoza [EU] (fezolinetant, neurokinin 3 receptor antagonist [NK3R]) was the first nonhormonal therapy approved in the US and EU for the treatment of menopausal-associated hot flashes based on the results (1,2,3) of the BRIGHT SKY (1,2,3) clinical trials. During menopause, fluctuations in oestrogen levels disrupt NK3R-mediated activation of hypothalamic KNDy neurons, leading to thermoregulatory dysfunction and VMS. In the Ph3 trials, ~60% of women saw a 50% reduction in hot flash frequency after 12 weeks, with 30% experiencing a 75% decrease and over 10% achieving complete elimination of symptoms, maintained at one year. Besides safety, another significant advantage of Veozah is its rapid onset of action, typically within a week, when hormone therapies may require up to a month to take effect. Bayer’s elinzanetant, another nonhormonal approach (NK1/3R antagonist) to stabilise the body’s internal thermostat is also in the late stages of development for VMS. Moreover, its dual targeting mechanism may offer an advantage over Veozah by addressing the underlying cause of both VMS and sleep disturbances, particularly considering the involvement of NK1R’s in the latter. In Jan 2024, Bayer reported positive topline results from Ph3 OASIS-1/-2 studies, followed by positive topline results from the Ph3 long-term OASIS-3 study in Mar 2024, demonstrating the effectiveness of elinzanetant in reducing moderate to severe VMS in postmenopausal women. With approval anticipated in 2025, elinzanetant is projected to achieve sales of $527 Mn by 2030 (based on Evaluate Pharma Jul 2024). However, despite the unmet need, sales predictions for elinzanetant are significantly lower than those for Veozah (projected at $1.5 Bn [Evaluate Jul 2024]). This discrepancy is likely due to Veozah’s first-mover advantage and established market dominance, which will have fostered greater familiarity among HCPs and patients. To drive peak sales, Bayer will likely have to focus on educating patients and providers on the benefits of dual NK1/3R antagonism to better position elinzanetant as a valuable and innovative treatment option in the menopause market.
Future Outlook and Market Opportunities
Amidst the evolving landscape of women’s health, the rising awareness of menopause and efforts to reduce workplace stigma are poised to significantly increase treatment-seeking behaviours among women. This demographic shift is underscored by the growing population of women over 50, who are becoming a pivotal segment of the workforce. A study by the UK Department for Work and Pensions highlights the economic benefits of supporting menopausal women in the workforce. If 600,000 more post-menopausal women remained employed full or part-time, it could add an extra £20 Bn and £9 Bn to the GDP, respectively. These findings underscore the importance of comprehensive strategies that not only improve health outcomes but also contribute to economic prosperity.
In the UK, businesses have increasingly implemented menopause policies supported by government initiatives. Legislation such as the Equality Act 2010 and the Health and Safety at Work Act 1974 provide protections for employees experiencing menopausal symptoms. Additionally, over 50 British organizations have been certified as “menopause-friendly” through accreditation developed by Henpicked: Menopause in the Workplace, possibly fuelled by the prevalence of workplace discrimination encountered by menopausal women, alongside the aim to retain this group of highly skilled and experienced women in the workforce, given that they typically reach the peak of their careers during this stage of life. This initiative is also expanding to the US, although lagging behind the UK, with New York City Mayor Eric Adams pledging to “change the stigma around menopause” and enhance policies and workplace environments to better accommodate the menopausal needs of working women. Additionally, under the Americans with Disabilities Act Amendments Act of 2008 (and applicable state anti-discrimination laws), symptoms of menopause or perimenopause that substantially interfere with daily activities may qualify as a disability.
Pharmaceutical firms are pivotal in driving innovation in menopause treatments by prioritizing R&D investments, understanding market demands, and addressing unmet needs. The Lancet’s recently published Menopause series advocates for a holistic approach beyond specific treatments, aiming to empower women with comprehensive information, decision-making tools, empathic clinical care, and workplace adjustments. Engaging stakeholders such as HCPs, patients, and regulators will be crucial in shaping the future of menopause care.
The staggering impact of menopause on the global economy, estimated at $150 BN in productivity loss and healthcare costs, underscores the urgent need to bridge care gaps and overcome medical barriers for millions of affected women. This challenge also presents a significant business opportunity. Successfully developing safe solutions to meet the demand for non-hormonal menopause products requires strategic investments in R&D, educating HCPs and patients, destigmatizing menopause discussions, and offering diverse treatment choices that align with women’s values and lifestyles.