Does vaginal estrogen carry the same risk as oral estrogen?
Hormone Treatment (Estrogen Pills and Creams) for Vaginal Menopause Symptoms
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
In my last video, I explained how the first-line treatment for mild to moderate vaginal dryness due to menopause are lubricants and moisturizers, and I called out the safest brands. If over-the-counter lubricants and moisturizers are insufficient to control the genitourinary symptoms of menopause, low-dose, local estrogen therapy is recommended, unless women have a history of hormone-dependent cancers like endometrial or breast. Local, meaning applied vaginally, as opposed to taken orally. Vaginal application is considered safer and more effective than systemic hormone therapy. A meta-analysis of 58 studies comparing vaginal to systemic estrogens found that vaginal estrogen therapy offered better symptom relief than estrogen pills, patches, or implants. In fact, many women who are on systemic menopausal hormone therapy have to add on supplemental vaginal estrogens to control symptoms.
Vaginal estrogens are available as a variety of creams, suppositories, and rings. Thirty randomized, control comparative trials have been performed, and there appears to be no difference in efficacy between the various preparations. However, they may take weeks before a noticeable alleviation of symptoms is detected, and two to three months before the full effect is achieved. Although year-long studies can clearly demonstrate vaginal estrogen’s benefit, studies as long as 12 weeks have failed to manifest superiority to placebo.
Some of the estrogen applied to the vulva or vagina is systemically absorbed, and therefore conveys the same black box FDA notice that oral estrogens carry, an all-caps warning of increased risk of “endometrial cancer, cardiovascular disorders, breast cancer and probable dementia.” Vaginal estrogen is considered safer, though, since it can be used at a much lower dose (as low as one-hundredth the oral dose). The Harvard Nurse’s Health Study did not find any increased risks associated with vaginal estrogen use over 18 years of follow-up. Randomized controlled trials lasting up to a year appear to confirm its safety, but there have been observational studies linking vaginal use to about a doubling of odds for endometrial cancer. But this was done back in the 1970s when higher estrogen doses were used. And a more recent study out of Denmark that found the same thing may have been confounded by concurrent oral estrogen exposure. Out of an abundance of caution, though, even low-dose localized estrogen may be contraindicated in hormone-dependent cancer survivors, to be on the safe side.
Breast cancer survivors suffering from GSM may want to consider vaginal DHEA instead. Oral DHEA doesn’t appear to offer any benefit, but in 2016 the FDA approved vaginal DHEA suppositories for pain during intercourse due to menopause. It’s converted locally into estrogen, and does not significantly affect systemic hormone levels. A downside is that it has to be administered nightly, whereas estrogen preparations are typically twice a week, or even every few months with the vaginal rings. For those who would rather an oral treatment, there’s ospemifene, a tamoxifen-type drug that has pro-estrogenic effects on the vaginal lining. However, it can actually double the rate of hot flashes and urinary tract infections in the short-term, and insufficient data is available for long-term safety.
Please consider volunteering to help out on the site.
- Eden JA. DHEA replacement for postmenopausal women: placebo or panacea? Climacteric. 2015;18(4):439-440.
- Scavello I, Maseroli E, Di Stasi V, Vignozzi L. Sexual health in menopause. Medicina (Kaunas). 2019;55(9):559.
- Pinkerton JV. Hormone therapy for postmenopausal women. N Engl J Med. 2020;382(5):446-455.
- Faubion SS, Sood R, Kapoor E. Genitourinary syndrome of menopause: management strategies for the clinician. Mayo Clin Proc. 2017;92(12):1842-1849.
- Crandall CJ, Diamant A, Santoro N. Safety of vaginal estrogens: a systematic review. Menopause. 2020;27(3):339-360.
- Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. 2018;26(6):603-610.
- Pinkerton JV, Kaunitz AM, Manson JE. Vaginal estrogen in the treatment of genitourinary syndrome of menopause and risk of endometrial cancer: an assessment of recent studies provides reassurance. Menopause. 2017;24(12):1329-1332.
- Di Donato V, Schiavi MC, Iacobelli V, et al. Ospemifene for the treatment of vulvar and vaginal atrophy: A meta-analysis of randomized trials. Part I: Evaluation of efficacy. Maturitas. 2019;121:86-92.
- Di Donato V, Schiavi MC, Iacobelli V, et al. Ospemifene for the treatment of vulvar and vaginal atrophy: A meta-analysis of randomized trials. Part II: Evaluation of tolerability and safety. Maturitas. 2019;121:93-100.
- Simunić V, Banović I, Ciglar S, Jeren L, Pavicić Baldani D, Sprem M. Local estrogen treatment in patients with urogenital symptoms. Int J Gynaecol Obstet. 2003;82(2):187-197.
- PREMARIN Vaginal Cream (conjugated estrogens). Pfizer.
- FDA approves Intrarosa for postmenopausal women experiencing pain during sex. US FDA. Nov 2016.
- Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol. 1998;92(4 Pt 2):722-727.
- Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016;2016(8):CD001500.
- Kelsey JL, LiVolsi VA, Holford TR, et al. A case-control study of cancer of the endometrium. Am J Epidemiol. 1982;116(2):333-342.
- Mørch LS, Kjaer SK, Keiding N, Løkkegaard E, Lidegaard Ø. The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study. Int J Cancer. 2016;138(6):1506-1515.
- Labrie F, Martel C, Bérubé R, et al. Intravaginal prasterone (Dhea) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol. 2013;138:359-367.
- Elraiyah T, Sonbol MB, Wang Z, et al. Clinical review: The benefits and harms of systemic dehydroepiandrosterone (Dhea) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3536-3542.
- Mitchell CM, Reed SD, Diem S, et al. Efficacy of vaginal estradiol or vaginal moisturizer vs placebo for treating postmenopausal vulvovaginal symptoms: a randomized clinical trial. JAMA Intern Med. 2018;178(5):681-690.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
In my last video, I explained how the first-line treatment for mild to moderate vaginal dryness due to menopause are lubricants and moisturizers, and I called out the safest brands. If over-the-counter lubricants and moisturizers are insufficient to control the genitourinary symptoms of menopause, low-dose, local estrogen therapy is recommended, unless women have a history of hormone-dependent cancers like endometrial or breast. Local, meaning applied vaginally, as opposed to taken orally. Vaginal application is considered safer and more effective than systemic hormone therapy. A meta-analysis of 58 studies comparing vaginal to systemic estrogens found that vaginal estrogen therapy offered better symptom relief than estrogen pills, patches, or implants. In fact, many women who are on systemic menopausal hormone therapy have to add on supplemental vaginal estrogens to control symptoms.
Vaginal estrogens are available as a variety of creams, suppositories, and rings. Thirty randomized, control comparative trials have been performed, and there appears to be no difference in efficacy between the various preparations. However, they may take weeks before a noticeable alleviation of symptoms is detected, and two to three months before the full effect is achieved. Although year-long studies can clearly demonstrate vaginal estrogen’s benefit, studies as long as 12 weeks have failed to manifest superiority to placebo.
Some of the estrogen applied to the vulva or vagina is systemically absorbed, and therefore conveys the same black box FDA notice that oral estrogens carry, an all-caps warning of increased risk of “endometrial cancer, cardiovascular disorders, breast cancer and probable dementia.” Vaginal estrogen is considered safer, though, since it can be used at a much lower dose (as low as one-hundredth the oral dose). The Harvard Nurse’s Health Study did not find any increased risks associated with vaginal estrogen use over 18 years of follow-up. Randomized controlled trials lasting up to a year appear to confirm its safety, but there have been observational studies linking vaginal use to about a doubling of odds for endometrial cancer. But this was done back in the 1970s when higher estrogen doses were used. And a more recent study out of Denmark that found the same thing may have been confounded by concurrent oral estrogen exposure. Out of an abundance of caution, though, even low-dose localized estrogen may be contraindicated in hormone-dependent cancer survivors, to be on the safe side.
Breast cancer survivors suffering from GSM may want to consider vaginal DHEA instead. Oral DHEA doesn’t appear to offer any benefit, but in 2016 the FDA approved vaginal DHEA suppositories for pain during intercourse due to menopause. It’s converted locally into estrogen, and does not significantly affect systemic hormone levels. A downside is that it has to be administered nightly, whereas estrogen preparations are typically twice a week, or even every few months with the vaginal rings. For those who would rather an oral treatment, there’s ospemifene, a tamoxifen-type drug that has pro-estrogenic effects on the vaginal lining. However, it can actually double the rate of hot flashes and urinary tract infections in the short-term, and insufficient data is available for long-term safety.
Please consider volunteering to help out on the site.
- Eden JA. DHEA replacement for postmenopausal women: placebo or panacea? Climacteric. 2015;18(4):439-440.
- Scavello I, Maseroli E, Di Stasi V, Vignozzi L. Sexual health in menopause. Medicina (Kaunas). 2019;55(9):559.
- Pinkerton JV. Hormone therapy for postmenopausal women. N Engl J Med. 2020;382(5):446-455.
- Faubion SS, Sood R, Kapoor E. Genitourinary syndrome of menopause: management strategies for the clinician. Mayo Clin Proc. 2017;92(12):1842-1849.
- Crandall CJ, Diamant A, Santoro N. Safety of vaginal estrogens: a systematic review. Menopause. 2020;27(3):339-360.
- Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. 2018;26(6):603-610.
- Pinkerton JV, Kaunitz AM, Manson JE. Vaginal estrogen in the treatment of genitourinary syndrome of menopause and risk of endometrial cancer: an assessment of recent studies provides reassurance. Menopause. 2017;24(12):1329-1332.
- Di Donato V, Schiavi MC, Iacobelli V, et al. Ospemifene for the treatment of vulvar and vaginal atrophy: A meta-analysis of randomized trials. Part I: Evaluation of efficacy. Maturitas. 2019;121:86-92.
- Di Donato V, Schiavi MC, Iacobelli V, et al. Ospemifene for the treatment of vulvar and vaginal atrophy: A meta-analysis of randomized trials. Part II: Evaluation of tolerability and safety. Maturitas. 2019;121:93-100.
- Simunić V, Banović I, Ciglar S, Jeren L, Pavicić Baldani D, Sprem M. Local estrogen treatment in patients with urogenital symptoms. Int J Gynaecol Obstet. 2003;82(2):187-197.
- PREMARIN Vaginal Cream (conjugated estrogens). Pfizer.
- FDA approves Intrarosa for postmenopausal women experiencing pain during sex. US FDA. Nov 2016.
- Cardozo L, Bachmann G, McClish D, Fonda D, Birgerson L. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol. 1998;92(4 Pt 2):722-727.
- Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016;2016(8):CD001500.
- Kelsey JL, LiVolsi VA, Holford TR, et al. A case-control study of cancer of the endometrium. Am J Epidemiol. 1982;116(2):333-342.
- Mørch LS, Kjaer SK, Keiding N, Løkkegaard E, Lidegaard Ø. The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study. Int J Cancer. 2016;138(6):1506-1515.
- Labrie F, Martel C, Bérubé R, et al. Intravaginal prasterone (Dhea) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol. 2013;138:359-367.
- Elraiyah T, Sonbol MB, Wang Z, et al. Clinical review: The benefits and harms of systemic dehydroepiandrosterone (Dhea) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3536-3542.
- Mitchell CM, Reed SD, Diem S, et al. Efficacy of vaginal estradiol or vaginal moisturizer vs placebo for treating postmenopausal vulvovaginal symptoms: a randomized clinical trial. JAMA Intern Med. 2018;178(5):681-690.
Motion graphics by Avo Media
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Hormone Treatment (Estrogen Pills and Creams) for Vaginal Menopause Symptoms
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Content URLDoctor's Note
Cancers, clots, and dementia? For more on the risks of systemic hormone “replacement” therapy for menopause, see How Did Doctors Not Know About the Risks of Hormone Therapy?
This was the second video in a three-part series. If you missed the first one, see The Best Moisturizers and Lubricants for Vaginal Menopause Symptoms.
Soy Milk for Vaginal Menopause Symptoms is next.
What about hot flashes? See Menopausal Hot Flashes Are Not Inevitable and Soy Foods for Menopause Hot Flash Symptoms.
You may also be interested in How to Delay the Age of Menopause with Diet and Lifestyle Factors.
For more on how to live your longest, healthiest life, preorder my new book How Not to Age. (As always, all proceeds I receive from all of my books are donated to charity.)
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