In early November, JAMA published an excellent article by FDA Commissioner Martin Makary (Updated Labeling for Menopausal Hormone Therapy) that gave new guidelines for FDA-supported uses of systemic and topical hormones (HRT or hormone replacement therapy) for the multiple conditions and symptoms that may adversely affect women going through the menopausal transition.
He also highlighted the 2003 FDA action instituting black-box warnings on all estrogen products, based on flawed analyses in the 2002 Women’s Health Initiative (WHI) report, that inappropriately induced fear of using such products in women and strongly discouraged physicians from prescribing them.
What Went Wrong?
The primary regulatory flaw was to use the randomized study data in the WHI, developed to study the efficacy of hormone replacement therapy in preventing cardiovascular disease in older women (average age mid-60’s), and to allow that study to affect its recommendations about hormone therapy intended to help women in their early 50’s manage disturbing physical symptoms experienced near and after menopause.
Substantial cardiovascular risk (not benefit) showed up in the WHI when those older women started hormone therapy, whereas the many observational studies in the 1990’s had appeared to show large reductions (40-50%) in cardiovascular disease from HRT. That changed outlook in 2002 was startling to many observers. The FDA got on board but issued warnings about all estrogen use even during or immediately after menopause.
The unfortunate result was that over two decades of women entering menopause in their early 50’s were largely denied the benefits of HRT for vasomotor symptoms. Women became fearful, there was immense pressure in the community and in hospital systems against any HRT, and many physicians stopped prescribing estrogen therapy at all.
What Was I Doing Then for My Patients?
I remember the details of these studies because I was there. My professional activities spanned the entire time period in question, more or less 1990 through the present.
During the 90’s I began prescribing hormones for many of my women patients, mainly for menopausal vasomotor symptoms (hot flashes, poor sleep, genitourinary issues) and to help maintain bone density before Fosamax was approved in 1995. I also was encouraged by the many observational HRT studies such as the continuing Nurses Study that showed cardiovascular benefit, but I didn’t really believe repeated findings of 40% reduction in heart disease among healthy women.
Helping Women
I felt it more important and clinically clear that HRT vastly reduced the vasomotor symptoms in affected women whom I treated. And I developed data in my practice that hormones with Fosamax (the first osteoporosis treatment) improved or protected bone density more effectively than Fosamax alone.
I continued to offer hormone therapy to women as appropriate for symptom relief throughout my practice until retiring 2 years ago. I never could professionally agree that estrogen cream for postmenopausal vaginal dryness should come with a black box warning and had to explain the inaccuracy of that labeling many times.
Correcting Course Going Forward
It is pleasing to see Commissioner Makary properly evaluate the science on menopausal hormone therapy and correct this decades-old damaging error. Perhaps accurate science will also become the norm that the CDC applies to its evaluation of vaccines.