12 March 2019

Summary

The Women’s Health Initiative (WHI) was certainly a milestone and a game changer in the history of menopause medicine. Before WHI, menopausal hormone therapy (HT) was considered a panacea, not only as a potent cure for menopause symptoms, but also as an effective strategy to keep women young forever and preventing all major chronic diseases of aging. However, WHI taught us that HT must be regarded as any other drug, to be cautiously prescribed after consideration of individual benefits and risks. Unfortunately, WHI results created a tsunami because of initial mis-interpretation of the data, which were amplified by the media and led to across the board banning of HT. Although more than 16 years elapsed since the first announcement of the preliminary results of the estrogen plus progestin arm of WHI, the study is still in focus, and a new research analyzes some aspects concerning its impact on the use of HT in the US [1]. The investigators followed women recruited for the SWAN study who returned for annual visits during 1996 to 2013. Women were 42-52 years old and were not menopausal at baseline. The study time frame allowed comparison of the pre-WHI period (up to 2002) with the post WHI period (after 2002). The focus was on initiation or continuation of HT among the 3018 participants. The results pointed at a highly significant drop in initiation (from 8.6% pre-WHI to 2.8% post-WHI), and a corresponding decrease in continuation of HT, from 84% to 62%. Menopausal symptom relief and provider advice were common HT initiation reasons both pre- and post-WHI, whereas prevention of heart disease or osteoporosis, which were often cited as reasons for initiation pre-WHI, were infrequently mentioned post-WHI. Interestingly, high in the list of reasons for discontinuation of HT were media reports and advices from healthcare providers. Lower in the list were the expected general reasons relevant to any medication – not needed anymore or suffering from adverse reactions (including undesired vaginal bleedings).

Commentary

Although the results of WHI should have been considered as reflecting the outcomes of HT initiated in women who, on average, were 65 years old or more than 10 years in menopause, they were extrapolated to all menopausal women. As well known, the consequences were much less initiation and much more discontinuation of HT all over the world. Exposure to the WHI data introduced real fear, both for women to use and physicians to recommend or prescribe HT. Higher risks for breast cancer in HT users probably became the main cause of worry among women. A telephone survey in the US, which investigated women’s perceptions about their greatest health concerns, showed that while more than a third pointed at breast cancer, only 8% regarded cardiovascular diseases as a problem [2]. It seems that the first announcements of WHI data, combined with wrong real-world insights about the commonest causes of morbidity and mortality in women, created this dramatic change in the use of postmenopausal hormones. Despite later analyses, which provided more accurate data on the impact of age or type of hormone use, mainly demonstrating favorable outcomes in younger women who use estrogen-alone therapy, the psychological impact of the initial results still prevails. I believe the quote from Manson and Kaunitz says it all [3]: “Women’s decisions regarding such therapy are now surrounded by anxiety and confusion. The new generation of medical graduates and primary care providers often lacks training and core competencies in management of menopausal symptoms and prescribing of hormonal treatments. Reluctance to treat menopausal symptoms has derailed and fragmented the clinical care of midlife women, creating a large and unnecessary burden of suffering”. Many reports compared the pre- versus post-WHI era regarding the use of HT, all showing a significant decline in prescriptions [4,5]. Some studies even demonstrated the downside of a lesser use of HT, primarily highlighting an increase in fracture rate [5]. The key for change lies in awareness and knowledge. Fortunately, many healthcare organizations and medical societies are putting efforts to promote unbiased information to both women and physicians. Updated guidelines and recommendations, as well as web-based education are now available for all. It is mandatory to put forward reassuring messages, such as that from NAMS that says, “For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture” [6]. The big question is of course whether these educational measures will be effective. Marko & Simon phrased it nicely as follows: “If this is enough to change clinical practice, however, remains to be seen, given the general fear of HT by many with prescriptive authority, and also the women in our care” [7]. As leaders in the field of menopause and midlife women’s health it is our duty to disseminate the relevant knowledge to the public and the health providers.

Amos Pines

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

References

1. Crawford SL, Crandall CJ, Derby CA, et al. Menopausal hormone therapy trends before versus after 2002: impact of the Women's Health Initiative study results. Menopause 2018 Dec 21.
   https://www.ncbi.nlm.nih.gov/pubmed/30586004
2. Mosca L, Jones WK, King KB, et al. Awareness, perception, and knowledge of heart disease risk and prevention among women in the United States. American Heart Association Women's Heart Disease and Stroke Campaign Task Force. Arch Fam Med 2000;9:506-15.
   https://www.ncbi.nlm.nih.gov/pubmed/10862212
3. Manson JE, Kaunitz AM. Menopause Management--Getting Clinical Care Back on Track. N Engl J Med 2016;374:803-806.
   https://www.ncbi.nlm.nih.gov/pubmed/26962899
4. Lagro-Janssen A, Knufing MW, Schreurs L, van Weel C. Significant fall in hormone replacement therapy prescription in general practice. Fam Pract 2010;27:424-9.
   https://www.ncbi.nlm.nih.gov/pubmed/20406789
5. Karim R, Dell RM, Greene DF, et al. Hip fracture in postmenopausal women after cessation of hormone therapy: results from a prospective study in a large health management organization. Menopause 2011;18:1172-7.
   https://www.ncbi.nlm.nih.gov/pubmed/21775911
6. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 2017;24:728-753.
   https://www.ncbi.nlm.nih.gov/pubmed/28650869
7. Marko KI, Simon JA. Clinical trials in menopause. Menopause 2018;25:217-230.
   https://www.ncbi.nlm.nih.gov/pubmed/28953214