Hormone Replacement in the Elderly, Is There a Benefit? by Jeffrey Dach MD

I frequently get this question: What about Menopausal Hormone Replacement Therapy (HRT) for women older than 65? Is there a benefit? Is there a risk? Should doctors offer the elderly woman over 65, menopausal hormone replacement (HRT)? Lucky for us, the answer was published in 2024 by Dr. Seo H. Baik in the Journal, Menopause. Dr. Baik examined Medicare records for 10 million senior Medicare women from 2007-2020.

Header image: Gare Saint-Lazare ou Le Chemin de fer, The Railway by Edouard Manet 1872 oil on canvas National Gallery of Art wikidata:Q214867
Accession number 1956.10.1 (National Gallery of Art), public domain. Courtesy of wikimedia commons.

Tremendous Benefits for Estrogen Monotherapy 

Dr. Baik compared the use of estrogen monotherapy in women over 65 to women who never used or discontinued use. Estrogen use was associated with almost 20% risk reduction in mortality. Other benefits were: 16% reduction in breast cancer 13% reduction in lung cancer, 12% reduction in colorectal cancer, and 11% reduction in heart attack. These benefits are seen in women aged 65 to 79 using low-dose transdermal or vaginal estrogen for managing menopausal symptoms like hot flashes and night sweats. (1)

Why the Reduction in Breast, Colon and Lung Cancer?

The authors did not speculate as to the reason why there was a reduction in these three cancers. I would suggest the mechanism is related to the role of estrogen in maintaining integrity of the genome. I will speculate that these anticancer benefits are due to the important role of estrogen in maintaining genome integrity which involves repairing damaged DNA, thus preventing cancer. I explain below.

Crosstalk Between Estrogen and DNA Repair

In 2022, Dr. Lia Yedidia-Aryeh studied the tight crosstalk between estrogen and DNA repair gene activation, finding estrogen is required for repairing DNA damage. In the elderly who are postmenopausal with long-term estrogen-deprived (LTED), the estrogen-deficient state will impair DNA repair mechanisms and lead to chronic DNA damage and mutation, a pro-carcinogenic mechanism.  Dr. Lia Yedidia-Aryeh writes:

We and others have shown that estrogen is required for intact DSB [double stranded break] [DNA] repair, since we found that DSB repair is impaired in ER-positive cells depleted for estrogen…Studies indicate that there is a tight crosstalk between estrogen and [DNA] repair. Estrogen regulates the expression of [DNA repair] factors and the activity of [DNA repair]. (4)

Cell survival depends on maintaining DNA repair mechanisms and genome integrity. This
in turn, is dependent upon maintaining estrogen signaling. Thus, all cells including tumor cells will desperately try to preserve estrogen signaling whenever threatened with estrogen deprivation. If genome integrity cannot be maintained in the damaged cell which is beyond repair, then estrogen signaling triggers apoptosis to eliminate the defective cell. This paradoxical estrogen-induced apoptosis after long-term estrogen deprivation, was recognized early on by Dr. V. Craig Jordan. (4-7)

Dr. Zsuzsanna Suba, Pathologist from Budapest Hungary

Estrogen Receptor alpha (ER-alpha) signaling is the major player in maintaining genome stability, working closely with the BRCA genes. In cells with damaged DNA, such as malignant tumor cells, ER-alpha signaling will trigger apoptosis, i.e. programmed cell death. In 2015, Dr. Zsuzsanna Suba writes:

Comprehensive analysis of experimental and clinical–epidemiologic results suggests that ER-alpha signaling is the chief safeguard of genome stability in strong interplay with DNA controlling and repairing systems, such as BRCA genes and their protein products…estrogen signaling recognizes and destroys malignant tumor cells by means of apoptotic mechanisms…(8)

Combined Estrogen/Progestin

The other part of Dr. Seo H. Baik’s study looked at the combined use of estrogen and a synthetic progestin finding 45% reduction in risk of endometrial cancer and 21% reduction in ovarian cancer. We do not use synthetic progestins which are endocrine disrupting chemicals. Rather we use natural progesterone which is also known to be an all purpose anti-cancer drug as discussed by Dr. Allan Lieberman, writing:

Use of progesterone has been linked to lower rates of uterine and colon cancers and may also be useful in treating other cancers such as ovarian, melanoma, mesothelioma, and prostate. Progesterone may also be helpful in preventing cardiovascular disease and preventing and treating neurodegenerative conditions such a stroke and traumatic brain injury…Physicians should have no hesitation prescribing natural progesterone, as the evidence is clear that progesterone does not cause breast cancer. Indeed, progesterone is protective and preventative of breast cancer. (9)

We also use another breast cancer preventive hormone in our formula: testosterone. Studies by Rebecca Glaser and Gary Donovits show a 40 percent reduction in breast cancer in tesosterone users. In addition, we use breast cancer preventive supplements such as iodine, DIM, resveratrol and berberine. (10-11)

So, yes, there is a benefit. What About Adverse Effects?

Adverse effects are related to excessive estrogen dosage, which may cause breast tenderness, fullness, or pain. The symptoms of estrogen excess will be obvious to the patient, who will then hold off using topical hormones for a few days. Once symptoms have resolved, they may then resume the HRT at a lower dosage.

What Are the Other Benefits of Estrogen?

In 2024, Dr. Chengmei Zhang studied the benefits of estrogen in the elderly, finding estrogen has potent neuroprotective properties. Estrogen plays an important bioenergetic role in mitochondrial metabolism in skeletal muscle in prevention of sarcopenia, a form of muscle wasting seen in the elderly. Dr. Zhang writes:

The deficiency of estrogen in menopause has been linked to changes in brain structure, connectivity, energy metabolism. Therewith, these are crucial factors in cognitive function and the risk of Alzheimer’s diseases. Besides, it leads to endocrine and metabolic dysfunction, resulting in osteoporosis, metabolic syndrome, and a tendency toward decreased muscle mass and strength. Estrogen’s influence on mitochondrial function is particularly relevant to aging, as it affects the production of ATP and the overall metabolic health of the brain. Estrogen decline in women skeletal muscle mass is usually related to sarcopenia, a prevalent disease observed in vulnerable elderly individuals.  (3)

Conclusion: Yes, as you have seen above, HRT has considerable health benefits even for the over-65 age group. Therefore, we are happy to  provide bioidentical hormone replacement formulas even for this age group.

If you liked this article, you might like my new book, Bioidentical Hormones 101, 2nd Edition (2025), paperback and ebook on Amazon. 

Click Here for link to ebook Bioidentical Hormones 101 Second Edition (2025) by Jeffrey Dach MD. This is a Three Volume Series e-book

Paperback Version of Bioidentical Hormones 101 second edition (2025). The paperback contains all three volumes.

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Bioidentical Hormones for Breast Cancer Survivors  Video Presentation

Articles with Related Interest:

Hormone Replacement for Breast Cancer Survivors Part One

Hormone Replacement for Breast Cancer Survivors Part Two

Estrogen Metabolism, Iodine, 2MEO Part Three

Testosterone for Breast Cancer Prevention and Treatment

All Bioidentical Hormone Articles

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my blog: www.jeffreydachmd.com 
Bioidentical Hormones 101 Second Edition
Menopausal Hormone Replacement, Health Benefits
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit by Jeffrey Dach MD
Heart Book by Jeffrey Dach MD

References:

1) Baik, Seo H., Fitsum Baye, and Clement J. McDonald. “Use of menopausal hormone therapy beyond age 65 years and its effects on women’s health outcomes by types, routes, and doses.” Menopause (2024): 10-1097.

Objectives: The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths.

Methods: Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia.

Results: Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%).

Conclusions: Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

A recent study analyzing data from 10 million senior Medicare women between 2007 and 2020 found that hormone therapy (HT) use beyond age 65 may be safe and even beneficial for managing menopause symptoms like hot flashes. The study suggests that age alone should not be a reason to discontinue HT, but that the type, route, and dose of therapy matter. It also found that estrogen monotherapy beyond age 65 was associated with reduced mortality and other health benefits.

2) Anagnostis, Panagiotis, et al. “Can menopausal hormone therapy be considered in postmenopausal women who are older than 60 years?.” Gynecological Endocrinology 41.1 (2025): 2468957.

However, low or ultra-low dose (25 or 12.5 μg of 17β-E2), preferably by the transdermal route, conveys the safest option for postmenopausal women in this age group who have
troublesome VMS, in the absence of contraindications (e.g. history of hormone-sensitive cancer.

3) Zhang, Chengmei, et al. “Research progress on the correlation between estrogen and estrogen receptor on postmenopausal sarcopenia.” Frontiers in endocrinology 15 (2024): 1494972.

Estrogen is a necessary sex steroid and potent neuroprotective hormone. It plays a multifaceted role beyond the reproductive system, extending its influence to the brain, skeletal muscle, and other organs. Estrogen’s role in cognition, mood, autonomic regulation, and neuroprotection involves interactions with neurotransmitters, neuromodulators in a distributed manner. Notably, the
impact of estrogen on mitochondrial metabolism in skeletal muscle is particularly significant due to a unique modulated bioenergetic profiles, synaptic plasticity, and neuronal health. The deficiency of estrogen in menopause has been linked to changes in brain structure, connectivity, energy
metabolism. Therewith, these are crucial factors in cognitive function and the risk of Alzheimer’s diseases. Besides, it leads to endocrine and metabolic dysfunction, resulting in osteoporosis, metabolic syndrome, and a tendency toward decreased muscle mass and strength. Estrogen’s influence on mitochondrial function is particularly relevant to aging, as it affects the production of ATP and the overall metabolic health of the brain. Estrogen decline in women skeletal muscle mass is usually related to sarcopenia, a prevalent disease observed in vulnerable elderly individuals. Therefore, estrogen is considered to play a crucial role in skeletal muscle homeostasis and motor ability, although the exact mechanism remains unclear. This paper reviews the literature on the impact of estrogen on postmenopausal skeletal muscle diseases and the underlying molecular mechanisms, especially in terms of mitochondrial metabolism. In summary, estrogen plays an important role in the health of skeletal muscle in postmenopausal women, and its impact on mitochondrial function and homeostasis offers potential targets for the development of new strategies to treat sarcopenia

4) Yedidia-Aryeh, Lia, and Michal Goldberg. “The Interplay between the Cellular Response to DNA Double-Strand Breaks and Estrogen.” Cells 11.19 (2022): 3097.

5) Lewis-Wambi, Joan S., and V. Craig Jordan. “Estrogen Regulation of Apoptosis: How Can One Hormone Stimulate and Inhibit?” Breast cancer research 11 (2009): 1-12.

6) Zach, L.; Yedidia-Aryeh, L.; Goldberg, M. Estrogen and DNA Damage Modulate mRNA Levels of Genes Involved in Homologous Recombination Repair In
Estrogen-Deprived Cells. J. Transl. Genet. Genom. 2022, 6, 266–280

7) Rajan, Arathi, et al. “Deregulated Estrogen Receptor Signaling and DNA Damage Response In Breast Tumorigenesis.” Biochimica et Biophysica Acta
(BBA)-Reviews on Cancer 1875.1 (2021): 188482.

8) Suba, Zsuzsanna. “DNA Stabilization by The Upregulation of Estrogen Signaling In BRCA Gene Mutation Carriers.” Drug Design, Development and Therapy (2015): 2663-2675.

9) Lieberman, A.; Curtis, L. In Defense of Progesterone: A Review of the Literature. Altern. Ther. Health Med. 2017, 23, 24–32.

10) Glaser, Rebecca L., Anne E. York, and Constantine Dimitrakakis. “Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study.” BMC cancer 19 (2019): 1-10.

11) Donovitz, Gary, and Mandy Cotten. “Breast cancer incidence reduction in women treated with subcutaneous testosterone: testosterone therapy and breast cancer incidence study.” European journal of breast health 17.2 (2021): 150.

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Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
my blog: www.jeffreydachmd.com 
Bioidentical Hormones 101 Second Edition
Menopausal Hormone Replacement, Health Benefits
Natural Thyroid Toolkit by Jeffrey Dach MD
Cracking Cancer Toolkit by Jeffrey Dach MD
Heart Book by Jeffrey Dach MD
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Last updated on October 26th, 2025 by Jeffrey Dach MD