29 October, 2012:

The United States Prevention Services Task Force (USPTF) has updated its 2005 recommendations on the use of postmenopausal hormones as a strategy to prevent chronic conditions in healthy women [1]. The USPSTF commissioned a review of the literature to update evidence about the benefits and harms of using menopausal hormone therapy to prevent chronic conditions, as well as whether the benefits and harms of hormone therapy differ by population subgroups defined by age, the presence of comorbid medical conditions, and the type, dose, and method of hormonal delivery.

This recommendation applies to postmenopausal women who are considering hormone therapy for the primary prevention of chronic medical conditions. It does not apply to women who are considering hormone therapy for the management of menopausal symptoms, such as hot flushes or vaginal dryness. It also does not apply to women younger than 50 years who have had surgical menopause.

The USPSTF recommends against the use of combined estrogen and progestin for the prevention of chronic conditions in postmenopausal women. The USPSTF recommends against the use of estrogen for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy. Recommendations are based on the evidence of both the benefits and harms of the service and an assessment of the balance.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision-making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

Comment

I dare say that outside the USA most women who are treated by HRT receive it because of menopausal symptoms. But, in the USA, many physicians were prescribing hormones just for primary prevention of chronic diseases, mainly cardiovascular. The only relevant approved indication of HRT relates to bone protection, therefore targeting solely the prevention of cardiovascular events and improved cognition has always been an off-label use. Early this year, the USPSTF published its systemic review on prevention of chronic conditions by HRT [2], which was the basis for the updated recommendations released online on October 23 [1].

The review concluded that 'Estrogen plus progestin and estrogen alone decreased risk for fractures but increased risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence. Estrogen plus progestin increased risk for breast cancer and probable dementia, whereas estrogen alone decreased risk for breast cancer'. This actually reflects the WHI study results; however, one should read carefully and pay attention to the phrasing of the updated recommendations. In the Introduction section it is clearly stated that 'This recommendation applies only to postmenopausal women who are considering hormone therapy for the primary prevention of chronic medical conditions. This is not a recommendation about the use of hormone therapy to treat menopausal symptoms, such as hot flashes or vaginal dryness; the USPSTF did not review the evidence related to this possible indication because it falls outside of the mission and scope of the USPSTF'. This actually places the new recommendations in the right perspective, which means that these are not applicable to the large subset of women who seek relief from their disturbing menopausal symptoms.

Another point to mention is the presentation of benefits and risks of HRT in a more rational way. For example, it is the first time that an official document states that 'There is adequate evidence that the use of estrogen alone results in a small reduction in the risk for developing or dying of invasive breast cancer'. The recommendations mention several other benefits of HRT, as well as several potential harms, and weigh them before concluding that 'Although the use of hormone therapy to prevent chronic conditions in postmenopausal women is associated with several potential benefits, there are substantial, well-documented harms to consider as well. The magnitude of adverse consequences associated with postmenopausal hormone therapy is moderate; the benefits are small in the case of combined estrogen and progestin therapy and small to moderate in the case of estrogen alone. Therefore, the USPSTF concludes with high certainty that there is zero to negative net benefit for the use of combined estrogen and progestin therapy for the prevention of chronic conditions and concludes with moderate certainty that there is no net benefit for the use of estrogen alone'.

Somehow, the issue of timing of HRT and the much better safety profile of hormone therapy seen in the early postmenopausal period did not gain enough importance in the recommendations, but received a small paragraph with an interesting explanation: 'No randomized trials have prospectively evaluated the effect of the timing of initiation of hormone therapy relative to menopause onset on associated benefits and harms. Post hoc subgroup analyses suggest an increased probability of harm with increasing age at initiation and longer duration of use, but these findings are not consistent across all trials and generally do not reach statistical significance.'

Although the document is quite detailed and accurate in the sense of the data it brings, one should not extrapolate the recommendations into the common clinical scenario where HRT is prescribed for menopause symptoms in young postmenopausal women. What remains still unknown is how the media will pick up this story, and what would be the interpretation of these recommendations in regard to hormone use in general.

Amos Pines

Department of Medicine 'T', Ichilov Hospital, Tel-Aviv, Israel

References

1. Moyer VA. Menopausal hormone therapy for the primary prevention of chronic conditions. U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2012 Oct 23. Free for downloading at http://annals.org/article.aspx?articleid=1384872 

2. Nelson HD, Walker M, Zakher B, Mitchell J. Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. Ann Intern Med 2012;157:104-1. http://www.ncbi.nlm.nih.gov/pubmed/22786830 

Content updated 23 October 2012