Afterword
Update, 2021: Estrogen Matters…Now More Than Ever
Since Estrogen Matters was published, we have continued to gather evidence about estrogen’s benefits and to attend closely to any studies that question our conclusions. And we have followed the WHI’s own continuing reports. Here is what we know as of 2021.
First and foremost, the WHI has walked back virtually all of their early alarmist findings. [1] In recent publications, they reported that estrogen does not increase “all cause mortality” or deaths from heart disease and cancer. Actually, they said, it increases longevity, most notably when begun within ten years of the last menstrual period. It is the best preventative for osteoporotic hip fracture. It is safe and effective when applied vaginally for local symptoms. And, in the most striking about-face from their 2003 headlines that HRT “did not have a clinically meaningful effect on health-related quality of life” for women in menopause, they stated in 2019 that “Hormone therapy is the most effective treatment for managing menopausal vasomotor symptoms.” [2] Now they write that “hot flashes and night sweats affect approximately 70% of midlife women and may persist for a decade or longer,” having significant adverse effects “on sleep, daily functioning, and quality of life.” And by the way, they add that “cognitive and mood symptoms often accompany disruptive hot flashes.” For these reasons, women with frequent, severe menopausal symptoms “may greatly benefit from hormone therapy.” Better late than never, but earlier would have been better for the countless thousands of women the WHI deprived of the “most effective” treatment.
As for women’s deep-seated fears of breast cancer as their main reason to avoid estrogen, in 2020 the WHI investigators reported a 23% decreased incidence of breast cancer among women randomized to estrogen—after 19 years of follow-up. It’s the combination of estrogen and progesterone (HRT), they still maintained, that raises the risk. [3] But two medical sleuths challenged that finding, which was not statistically significant in 2002, reporting it was due to a statistical misinterpretation: The women on HRT did not have an increased risk; the control group had a reduced risk, because many of the women in that group had been on estrogen before the study! When they were removed from analysis, the supposed increased risk of HRT vanished. [4]
Finally, more good news for the many women concerned about the safety of pregnancy, when estrogen rises tenfold, following breast cancer. A collaborative study from research institutions around the world concluded that pregnancy following treatment of breast cancer had no negative effect on prognosis, regardless of estrogen receptor assay positivity, after a median follow-up of 7.2 years. And a retrospective, international cohort study of 1,252 breast cancer patients with BRCA mutations, published in 2020, reported no increased risk of breast cancer recurrence associated with pregnancy following treatment. [5]
Nonetheless, as of this writing in 2021, we have yet to see an NIH press conference convened to reassure women of the benefits of estrogen and publicly explain what was wrong with the original WHI scare stories that many doctors still hold as gospel. On the contrary, whenever someone manages to assemble yet another huge vat of numbers and pull out a tiny but spurious “finding” that can alarm women, headlines follow like a dog after a biscuit. In 2019, the prestigious British journal The Lancet published a paper claiming that HRT increases the risk of breast cancer, generating the inevitable headlines and fears, and so we scrutinized it closely. Once again, the data did not support the alarm. [6]
We are still waiting for that press conference.
_________________________________
[1] Stuenkel CA, Manson JE. Women’s Health – Traversing medicine and public policy. N Engl J Med 2021;384: 2073-6.
[2] Shifren JL, Crandall CJ, Manson JE. Menopausal hormone therapy. JAMA 2019;321:2458-9.
[3] Chlebowski RT, Anderson GL, Aragaki AK. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative Randomized Clinical Trials. JAMA 2020;324:369-80.
[4] Hodis HN, Sarrel PM. Menopausal hormone therapy and breast cancer: what is the evidence from randomized trials? Climacteric 2018;21:521-8.
[5] Lambertini M, Kroman N, Ameye L. Long-term safety of pregnancy following breast cancer according to estrogen receptor status. J Natl Cancer Inst 2018;110:426-9.
Lambertini M, Ameye L, Hamy A-S, et al. Pregnancy after breast cancer in patients with germline BRCA mutations. J Clin Oncol 2020;38:3012-23.
[6] https://peterattiamd.com/hormone-therapy-and-breast-cancer/
First and foremost, the WHI has walked back virtually all of their early alarmist findings. [1] In recent publications, they reported that estrogen does not increase “all cause mortality” or deaths from heart disease and cancer. Actually, they said, it increases longevity, most notably when begun within ten years of the last menstrual period. It is the best preventative for osteoporotic hip fracture. It is safe and effective when applied vaginally for local symptoms. And, in the most striking about-face from their 2003 headlines that HRT “did not have a clinically meaningful effect on health-related quality of life” for women in menopause, they stated in 2019 that “Hormone therapy is the most effective treatment for managing menopausal vasomotor symptoms.” [2] Now they write that “hot flashes and night sweats affect approximately 70% of midlife women and may persist for a decade or longer,” having significant adverse effects “on sleep, daily functioning, and quality of life.” And by the way, they add that “cognitive and mood symptoms often accompany disruptive hot flashes.” For these reasons, women with frequent, severe menopausal symptoms “may greatly benefit from hormone therapy.” Better late than never, but earlier would have been better for the countless thousands of women the WHI deprived of the “most effective” treatment.
As for women’s deep-seated fears of breast cancer as their main reason to avoid estrogen, in 2020 the WHI investigators reported a 23% decreased incidence of breast cancer among women randomized to estrogen—after 19 years of follow-up. It’s the combination of estrogen and progesterone (HRT), they still maintained, that raises the risk. [3] But two medical sleuths challenged that finding, which was not statistically significant in 2002, reporting it was due to a statistical misinterpretation: The women on HRT did not have an increased risk; the control group had a reduced risk, because many of the women in that group had been on estrogen before the study! When they were removed from analysis, the supposed increased risk of HRT vanished. [4]
Finally, more good news for the many women concerned about the safety of pregnancy, when estrogen rises tenfold, following breast cancer. A collaborative study from research institutions around the world concluded that pregnancy following treatment of breast cancer had no negative effect on prognosis, regardless of estrogen receptor assay positivity, after a median follow-up of 7.2 years. And a retrospective, international cohort study of 1,252 breast cancer patients with BRCA mutations, published in 2020, reported no increased risk of breast cancer recurrence associated with pregnancy following treatment. [5]
Nonetheless, as of this writing in 2021, we have yet to see an NIH press conference convened to reassure women of the benefits of estrogen and publicly explain what was wrong with the original WHI scare stories that many doctors still hold as gospel. On the contrary, whenever someone manages to assemble yet another huge vat of numbers and pull out a tiny but spurious “finding” that can alarm women, headlines follow like a dog after a biscuit. In 2019, the prestigious British journal The Lancet published a paper claiming that HRT increases the risk of breast cancer, generating the inevitable headlines and fears, and so we scrutinized it closely. Once again, the data did not support the alarm. [6]
We are still waiting for that press conference.
_________________________________
[1] Stuenkel CA, Manson JE. Women’s Health – Traversing medicine and public policy. N Engl J Med 2021;384: 2073-6.
[2] Shifren JL, Crandall CJ, Manson JE. Menopausal hormone therapy. JAMA 2019;321:2458-9.
[3] Chlebowski RT, Anderson GL, Aragaki AK. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative Randomized Clinical Trials. JAMA 2020;324:369-80.
[4] Hodis HN, Sarrel PM. Menopausal hormone therapy and breast cancer: what is the evidence from randomized trials? Climacteric 2018;21:521-8.
[5] Lambertini M, Kroman N, Ameye L. Long-term safety of pregnancy following breast cancer according to estrogen receptor status. J Natl Cancer Inst 2018;110:426-9. Lambertini M, Ameye L, Hamy A-S, et al. Pregnancy after breast cancer in patients with germline BRCA mutations. J Clin Oncol 2020;38:3012-23.
[6] https://peterattiamd.com/hormone-therapy-and-breast-cancer/