Conventional medicine has long been wedded to the “one pill for one ill” therapeutic model. But cracks in that model are finally starting to show. A large-scale study, partially funded by the NIH, TAME, hopes to launch this year, to investigate whether the popular type 2 diabetes drug metformin can delay any number of diseases of aging. A small-scale study, VIBRANT, is already up and running, looking to see whether the immunosuppressant drug rapamycin can slow the aging of ovaries and is poised to serve as a springboard for future longevity trials with this promising drug.
But what really struck me about these two trials was that we already have an anti-aging therapy that is likely far more potent than either metformin or rapamycin. It’s been staring us in the face for decades -- hormone replacement therapy for women. While HRT has always been one of the cornerstones of my practice, it fell victim to a massive, and massively misguided, NIH study the Women’s Health Initiative, which published its first results back in 2002. The study’s original conclusions, and the media firestorm that ensued, so stigmatized HRT that only in the past 5 years or so has mainstream medicine been able to fairly consider its merits. The best example I know of is a rigorous, clear-eyed evaluation of HRT is a 2022 review of the literature in The Cancer Journal by two eminent University of Southern California researchers, a cardiologist and a biostatistician, whose title couldn’t be more self-explanatory: “Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It’s About Time and Timing.”
Timing is where the first WHI report went seriously awry. The women in the randomized controlled studies were, on average, in their sixties, and more than ten years beyond menopause. In this group, there was an uptick in heart attacks and stroke and a small, but not insignificant, increase in breast cancers. What happened in these studies was that the health gains enjoyed by the younger women, in their fifties, were washed out by the harms experienced by the older group. Several years later, the age/timing issue revealed itself in the data and a new mainstream orthodoxy emerged, still prevalent today: HRT is fine, or at least OK, for these younger women, to treat menopausal symptoms like hot flashes, but using it to delay or mitigate life-threatening diseases isn’t worth the possible health risk.
The Cancer Journal review blows that thinking out of the water. The authors pull together a raft of randomized trials, arterial imaging studies and animal studies to arrive at some hard-to-argue-with stats. The women on HRT, under the age of 60 and/or within 10 years of the onset of menopause, experienced a 32% reduction in coronary heart disease and, even more striking, a 39% reduction in death from any cause -- “all-cause mortality.” (Keep in mind, in the U.S., heart disease kills 1 out of 3 women.) This is proof, the USC researchers explain, of what they call the “healthy endothelium” hypothesis. In other words, treat women patients before the common post-menopausal calcification occurs in the lining of their heart vessels and good things happen, not only less heart disease but all the other familiar benefits accrue of keeping estrogen levels at youthful levels, including: protection against osteoporosis, “brain fog,” skin wrinkling, vaginal dryness, loss of libido.
I should mention that there was a small increase in breast cancer risk in some of the trials under review, a decrease in others. The range was 14 fewer cases per 10,000 women over a year of HRT to 6 additional cases. Contrast this with statins, a CVD therapy embraced by the medical mainstream, where the small increase in breast cancer risk exceeded the “rare” threshold in some of the trials. And while statins, which have never been shown to decrease the risk of heart attack in women who haven’t already had one, increases the risk of diabetes, HRT lowers it..
The only caveat I would attach to The Cancer Journal review is that, in my practice, I don’t automatically rule out women over 60 for HRT therapy. Theirs was the generation that had HRT taken off the table by the WHI report. If, after I test for calcification, their arteries are clear, or their risk is mitigated by statin therapy, I put HRT back on the table. Why should these patients continue to be victimized by incorrect assumptions derived from a poorly interpreted study?
Of course, most conventional doctors would take a “many pills'' approach to the many age-related ills my female patients may be experiencing – bisphosphonates for osteoporosis, statins for CVD prevention, SSRIs for brain fog/night sweats/hot flushes, vaginal estradiol tablets for dryness, and so on. I’d prefer to prescribe HRT which can address all of these conditions as a primary prevention intervention. That’s my idea of a potent longevity medicine!