According to new research published this month in Europe's leading cardiology journal, the European Heart Journal, women who take hormone replacement therapy (HRT) to treat menopause symptoms do not have a higher than usual risk of heart attack, especially if they use a cream or skin patch(1).
The observational study of over 698,098 healthy Danish women aged 51-69 represents the latest turn on the ongoing debate over the safety of HRT and suggests that large, widely publicized studies linking HRT use to cardiovascular events and breast cancer may not be the last word on treatment. As a result of the declining sales of hormonal replacement therapy (HRT) in recent years caused by such safety concerns, non-hormonal treatments for menopausal symptoms had an estimated revenue potential of over $535million across the US and five major EU markets** in 2007, according to a new report* from independent market analyst Datamonitor. However, with current developmental drugs failing to provide a substantial reduction in symptoms, their use is expected to be limited to a minority of patients who are unable to take HRT.
In spite of its certainty, there exists great variation in women's experiences of the menopause; while some women do not encounter any symptoms during menopause or only have a few symptoms, others develop severe and distressing symptoms which significantly decrease their quality of life and lead them to seek medical treatment.
Of the wide range of symptoms that women going through the menopause may experience, hot flashes and night sweats (also known as vasomotor symptoms) are the most common, affecting approximately 75% of women aged over 50 years(2). Such symptoms can cause extreme anxiety for sufferers in work or social situations.
Despite the large proportion of women who experience symptoms of the menopause, not all will seek treatment. On the basis of a large, US-based study reporting that approximately 60% of symptomatic women consult a healthcare provider for help with their symptoms(3), Datamonitor estimates that over 68 million women will seek treatment for menopausal symptoms in the seven major markets (7MM)** in 2008. A number of factors could prevent a woman from receiving drug treatment says Datamonitor central nervous system (CNS) analyst Charlotte Mackey. “These include symptoms not being severe enough to impact on quality of life and prompt treatment-seeking behaviour, a physician's decision that symptoms are not severe enough to warrant treatment, a lack of patient knowledge regarding the available drug treatments, as well as patients' reluctance to interfere with what they consider to be a natural process,” she says.
Hormone replacement therapy (HRT) serves to increase a woman's levels of the female hormones oestrogen and progestogen, which the ovaries gradually stop producing as she enters the menopause. Available treatment options include both estrogen only and estrogen and progestogen combination therapies.
HRT has formed the mainstay of treatment for menopausal symptoms for almost 60 years. Such treatments are highly effective and have been reported to reduce hot flashes and their frequency in postmenopausal women by 70-90% (4,5).However, since 2002 large studies have generated much controversy and concern over the safety of HRT. Arguably the most influential of these was the Women's Health Initiative (WHI) trials(6), which linked use of HRT to an increased risk of breast cancer and certain cardiovascular diseases. The publication of this and similar studies substantially reduced physician and patient confidence in HRT and led to high rates of treatment discontinuation. As a result, sales of HRT products fell sharply and demand increased for safe and effective non-hormonal treatment options. Key opinion leaders interviewed by Datamonitor agree that six years after the initial publication of the WHI trial data, alarm raised by media reporting continues to generate mistrust of HRT for menopausal symptoms among patients, Ms. Mackey says.
“The key opportunity for non-hormonal treatments of menopausal symptoms lies in capturing sales that have been lost by the hormonal treatments since 2002. On this basis, Datamonitor estimates that non-hormonal treatments to have revenue potential of at least $535million across the US and 5EU markets in 2007,” she says.
In order to be widely prescribed, the ideal non-hormonal treatment for symptoms of the menopause must possess comparable efficacy to HRT, minimal side effects, and be able to be safely co-administered with commonly prescribed drugs. “Crucially, such a drug must carry no increased risk of breast cancer or cardiovascular problems,” she adds.
Despite increased interest in non-hormonal treatment options since the 2002 publication of the WHI, few non-hormonal drugs are presently in development for the treatment of menopausal symptoms; there are only four such drugs currently in clinical trials compared to the twelve hormonal treatments in development. The current non-hormonal pipeline is dominated by reformulations of centrally acting drugs, principally antidepressants, which have historically been the most extensively studied pharmacological alternatives to HRT. The remainder of the non-hormonal pipeline comprises a reformulation of a marketed anticonvulsant drug. Although regulatory approval of antidepressants for menopausal symptoms may represent a benefit to the estimated 25% of women undergoing the menopausal transition who experience depressive symptoms, Ms. Mackey says. “Ultimately, however, Datamonitor believes that their dominance renders the non-hormonal development pipeline weak and lacking in innovation.”
As well as being few in number, available clinical trial data demonstrates that developmental non-hormonal drugs do not match the effectiveness of conventional hormonal treatments in reducing hot flashes and night sweats.
For example, at 12 weeks, 100mg of Wyeth's Pristiq (desvenlafaxine) has been found to reduce hot flashes by 64%. By comparison, the market leading hormonal treatment—Premarin (conjugated equine estrogen—CEE), which is also marketed by Wyeth— reduces the frequency of hot flashes by 94% at 12 weeks, Ms. Mackey says. “Although presently experiencing regulatory delays, Datamonitor believes Pristiq could by the first non-hormonal treatment to enter the menopause market in early 2009.
“Key advantages of Pristiq include its rapid onset of action and ability to improve sleep quality and mood while not negatively effecting sexual function,” she says.
At first glance, the future for non-hormonals appears bleak, with future sales revenue unlikely to rival that of HRT products, which generated combined sales of $1.57 billion**. Nevertheless, Datamonitor believes that they will be welcomed as useful additional treatment options by doctors for the estimated 115 million women in the 7MM who are eligible for drug intervention for their troublesome menopausal symptoms, Ms. Mackey says.
“In particular, it is expected that demand for a safe non-hormonal treatment for symptoms of the menopause will be high among key patient groups for whom HRT is not a suitable treatment option. These core groups include breast cancer patients and survivors of breast cancer as well as women with certain cardiovascular disorders.
“Furthermore, highly symptomatic women who do not wish to receive HRT due to profound safety concerns, and mildly symptomatic women who do not believe their symptoms are severe enough to warrant HRT use also represent potential patients for companies developing of non-hormonal treatments for menopausal symptoms,” she says.
* Stakeholder Opinions: Non-hormonal Treatments for Menopausal Symptoms.
**Seven major markets: UK, US, France, Germany, Italy, Japan and Spain.
References
1. Løkkegaard et al. (2008). Available from: http://eurheartj.oxfordjournals.org/cgi/content/abstract/
2.Avis et al. (2001).
3. Williams et al. (2007)
4. Notelovitz et al. (2000).
5. Nand et al. (1998).
6. Rossouw et al. 2002.
Datamonitor's report Stakeholder Opinions: Non-hormonal Treatments for Menopausal Symptoms provides analysis of the commercial and clinical potential of non-hormonal treatments for menopausal symptoms based on seven key opinion leader interviews, with focus on the treatment of vasomotor symptoms.
