04 Sep The Study That Scared a Generation Off Hormone Therapy
In July 2002, the Women's Health Initiative (WHI) published initial findings from a large-scale randomized clinical trial evaluating hormone replacement therapy (HRT) in postmenopausal women. National news outlets quickly broadcast alarming, sensationalized headlines claiming that hormone replacement therapy significantly increased the risk of invasive breast cancer, heart attacks, stroke, and blood clots. Almost overnight, millions of women worldwide abruptly stopped taking their prescribed hormone medications, while medical practitioners drastically curtailed HRT prescriptions. For over two decades, pervasive fear surrounding hormone replacement therapy dominated clinical practice, leaving an entire generation of menopausal women to suffer through unmitigated hot flashes, night sweats, bone density loss, severe sleep disruption, cognitive decline, mood disturbances, and metabolic dysfunction. According to the North American Menopause Society, hormone therapy remains one of the most effective treatments for menopausal symptoms, and current evidence supports its safety and efficacy for appropriately selected women, particularly when initiated in early menopause.
However, subsequent extensive scientific re-analyses of the original WHI trial data over the past twenty years have exposed fundamental methodological flaws in how the study was designed, conducted, and publicly reported. The average age of WHI study participants was 63 years old — over a decade older than the typical age of natural menopause onset in North America. Most trial participants possessed underlying baseline cardiovascular risks and were administered older synthetic oral hormone formulations (conjugated equine estrogens and synthetic medroxyprogesterone acetate) rather than modern, body-identical hormones. Today, leading global medical societies recognize that therapeutic timing and hormone selection are paramount. When initiated during perimenopause or early menopause, bioidentical hormone replacement may represent a safe, transformative, and highly effective pillar of comprehensive menopause management.
[caption id="attachment_75895" align="aligncenter" width="500"] Photo by Nguyễn Tiến Thịnh [/caption]
Dr. Mikkola[/caption]
Tomi Mikkola MD
Associate Professor
Helsinki University Hospital
Department of Obstetrics and Gynecology
Helsinki, Finland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In Finland we have perhaps the most comprehensive and reliable medical registers in the world. Thus, with my research group I have conducted various large studies evaluating association of postmenopausal hormone therapy use and various major diseases (see e.g. the references in the B;MJ paper). There has been various smaller studies indicating that hormone therapy might be protective for all kinds of dementias, also Alzheimer’s disease.
However, we have quite recently shown that hormone therapy seems to lower the mortality risk of vascular dementia but not Alzheimer’s disease (Mikkola TS et al. J Clin Endocrinol Metab 2017;102:870-7). Now in this upcoming BMJ-paper we report in a very large case-control study (83 688 women with Alzheimer’s disease and same number of control women without the disease) that systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer’s disease.
Furthermore, this risk increase is particularly in women using hormone therapy long, for more than 10 years. This was somewhat surprising finding, but it underlines the fact that mechanisms behind Alzheimer’s disease are likely quite different than in vascular dementia, where the risk factors are similar as in cardiovascular disease. We have also shown how hormone therapy protects against cardiovascular disease, particularly in women who initiate hormone therapy soon after menopause. 
