Are there Optimum Estrogen Levels for Preventing Osteoporosis with MHT?
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“I would love to hear about optimum estrogen levels to prevent bone loss and decrease heart disease risk. I am having a hell of a time finding a doctor who listens….An older NIH study from 1992 says the minimum level of serum estradiol to prevent postmenopausal bone loss is a value of 60 pg/ml. But I also have heard MHT should treat symptoms NOT serum levels. Help!”
-Via The Vajenda
Short Take
Experts do not recommend checking estrogen levels (meaning estradiol) while on menopausal hormone therapy (MHT). We start MHT based on symptoms, not levels. For those taking MHT for osteoporosis prevention, we have studies that guide us regarding dose. A provider checking estradiol levels to see if you are on the “right dose” is a red flag that you are not getting standard of care.
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Bone is constantly being built, but it is also constantly being broken down by the body. The balance favors building bone until our mid-twenties, which is when we achieve peak bone mass (think of this as your bone bank). Estrogen inhibits the breakdown of bone, and so there is an acceleration of bone loss with menopause. This is why estrogen in MHT is helpful because it prevents the normal accelerated loss of bone in menopause.
Research has determined the dose of estrogen for osteoporosis prevention based on studies that look at fractures, bone density, and blood tests that tell us about bone health as well as hormone levels. Longer and larger studies are better for looking at fractures, but smaller and shorter studies can also tell us a lot using bone density and blood tests. This post I wrote for The Hormone Menoverse Guide breaks down how we determine the risk for osteoporosis and when to start medications to reduce that risk.
We know from the Women’s Health Initiative (WHI) that Premarin 0.625 mg daily actually increases bone density and decreases the risk of fractures. During the WHI, women who took Premarin with or without medroxyprogesterone acetate had six fewer hip fractures per 10,000 women and six fewer vertebral fractures per 10,000 women compared with those who took placebo. Other studies have looked at lower doses, and 0.45 mg of Premarin offers similar protection to 0.625 mg. Even 0.3 mg of Premarin can stop bone loss.
What about estradiol? All of the standard doses protect the bones, meaning 25 mcg-100 mcg patch (or other transdermal equivalent) or 0.5-2 mg of oral estradiol. Studies tell us that even a 14 mcg patch can protect the bones, although this dose likely provides less gains in bone density than the more standard doses.
I’m not sure which specific study or paper is referenced in the question, but the idea of a critical level of estradiol to protect bone health in menopause has been the subject of a fair amount of research. Estradiol levels are lower in the early to mid part of the follicular phase (first part of the cycle), and they range from 20-80 pg/ml. In menopause, estradiol levels are typically < 20 pg/ml. For many years, it was believed that the minimal estradiol level for bone health was 30-45 pg/ml, but some papers did propose 60 pg/ml. Further work suggests that bone is exquisitely sensitive to estradiol. Some studies have even shown a difference in bone health for women whose estradiol levels are in the lowest menopausal range, < 5 pg/ml, vs. those who have levels that are slightly higher, > 5-10 pg/ml. This makes sense as a 14 mcg estradiol patch prevented bone loss, but estradiol levels only went up slightly and were still in the menopausal range.
While estradiol levels are important in research studies, they are not important in managing MHT for the prevention of osteoporosis because we know the doses of estrogen that work for bone protection. Neither the Menopause Society nor the Endocrine Society recommend checking estradiol levels for reasons related to bone health. The Menopause Society 2021 Position Statement on Osteoporosis doesn’t mention estradiol levels.
When starting MHT for the purpose of osteoporosis prevention for women ages 45 and older, most experts would recommend a minimum of a 25 mcg estradiol patch (or other transdermal equivalent), 0.5 mg oral estradiol, or 0.45 mg of Premarin. However, the lower doses mentioned above (14 mcg patch and 0.3 mg of Premarin) still offer protection. Whether these lower doses are appropriate for a given individual at higher risk for osteoporosis isn’t a question I can answer here.
I know many practitioners are pushing the idea of checking your estrogen levels for all kinds of reasons, but this is not evidence-based medicine. It is a way for them to make money because they can charge you for interpreting the tests.
Does Progesterone or Progestins Have Any Benefit on Bone?
The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial randomly assigned women to placebo or four different regimens of Premarin-based MHT. Premarin alone performed as well bone-wise as Premarin with either medroxyprogesterone acetate (Provera, which is a progestin) or Premarin plus progesterone. However, norethindrone acetate, another progestin, does appear to have some effect on bone health. This is likely because during the metabolism of norethindrone acetate, small amounts of estrogen (ethinyl estradiol) are produced.
What About Cardiovascular Disease?
Some data shows a reduced rate of cardiovascular disease for women who start MHT before age 60/within 10 years of menopause, and other shows a neutral effect. The best way to summarize this is any benefit for the heart offsets any potential negative effects for women who are otherwise at low risk. Here is the quote:
“For healthy symptomatic women aged younger than 60 years or within 10 years of menopause onset, the favorable effects of hormone therapy on CHD and all-cause mortality should be considered against potential rare increases in risks of breast cancer, VTE, and stroke.”
(CHD is coronary heart disease, and VTE is venous thromboembolism or a blood clot).
The Menopause Society and the Endocrine Society do not currently recommend starting hormone therapy for the purpose of reducing the risk of cardiovascular disease.
Thanks for the question, and keep them coming!
References
NAMS Position Statement. The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2022;29:767-794.
Ettinger B, Ensrud KE, Wallace R, Johnson KC, Cummings SR, Yankov V, Vittinghoff E, Grady D. Effects of ultralow-dose transdermal estradiol on bone mineral density: a randomized clinical trial. Obstet Gynecol. 2004 Sep;104(3):443-51.
Delmas PD, Pornel B, Felsenberg D, Stakkestad JA, Radowicki S, Garnero P, Hardy P, Dain MP, Petitier B; International Study Group. Three-year follow-up of the use of transdermal 17beta-estradiol matrix patches for the prevention of bone loss in early postmenopausal women. Am J Obstet Gynecol. 2001 Jan;184(2):32-40.
Reginster JY, Sarlet N, Deroisy R, Albert A, Gaspard U, Franchimont P. Minimal levels of serum estradiol prevent postmenopausal bone loss. Calcif Tissue Int. 1992 Nov;51(5):340-3.
Barbieri RL. Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 1992;166:740–745.
Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal
S, Ettinger B (1998) Endogenous hormones and the risk of hip and vertebral fractures among older women. Study of Osteoporotic Fractures Research Group. N Engl J Med 339(11):733–738.
Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME. Challenges to the measurement of estradiol: an endocrine society position statement. J Clin Endocrinol Metab. 2013 Apr;98(4):1376-87.
Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society. NAMS Position Statement. Menopause;2021:28:973-997.
Eastell R, Rosen CJ, Black DM. et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2019;104:1595-1622.
The Writing Group for the PEPI. Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA. 1996;276(17):1389.
Hadji P, Colli E, Regidor P.-A. Bone health in estrogen-free contraception. Osteoporosis International 2019;30:2391–2400.
Question on a different topic. Fascinating (and horrifying) article recently in The Guardian on GSM and UTIs etc in menopausal women (https://www.theguardian.com/society/2023/dec/17/millions-of-women-are-suffering-who-dont-have-to-why-its-time-to-end-the-misery-of-utis). Wondering what your take is on whether vaginal estrogen should be taken at a certain point, preventively, even if we’re already using systemic estrogen and don’t have any GSM symptoms, or is systemic estrogen enough?
Are there any studies that show a clear benefit on exercising with weights and other load bearing exercise for helping with bone density? I can’t have oestrogen therapy because of breast cancer 7 years ago. I use weights at the gym three times a week and also climb (indoor climbing) twice a week. Hoping this is enough...?