Bioidentical hormone replacement therapy (BHRT) and Cancer Survivors
Bioidentical hormone replacement therapy (BHRT) is increasingly used for managing
menopausal symptoms and addressing age-related hormone decline, but its application in
cancer survivors—especially breast and prostate cancer—is complex due to concerns about
cancer recurrence and progression. Let’s explore the risks and benefits of using bi-est (estradiol
+ estriol), estradiol, estriol, progesterone, testosterone, and DHEA in these contexts, based on
the latest research.
Breast Cancer Survivors
The use of BHRT after breast cancer remains controversial, as hormone receptor-positive
(ER+/PR+) tumors, which comprise a significant proportion of breast cancers, can be sensitive
to exogenous hormones like estrogens and progesterone.
Estradiol & Estriol (Bi-Est)
- Estradiol : This is the most potent form of estrogen and has been linked to increased risk
in breast cancer survivors, particularly in ER+ and PR+ tumors. Studies suggest that
systemic estradiol therapy should be avoided in ER+ breast cancer survivors, as it may
fuel tumor recurrence by activating estrogen receptors in residual cancer cells. Some
studies highlight a modest but statistically significant increased risk of recurrence with
estradiol therapy post-treatment. - Estriol : This weaker estrogen metabolite has been proposed as a safer alternative.
Unlike estradiol, estriol has a weaker binding affinity to estrogen receptors and is
thought to exert protective effects by occupying estrogen receptors without stimulating
cancer growth. Limited studies in breast cancer survivors suggest estriol may have a
better safety profile, particularly for ER+ tumors, but data is scarce and mostly
observational. - Relative risk: A cohort study reviewing estrogen replacement therapy in breast cancer
survivors (specifically those on estriol ) showed a lower recurrence risk (RR: 0.65–0.75)
compared to estradiol. However, the protective benefits are not conclusive, and
ongoing vigilance is required.
Progesterone
- In hormone-receptor-positive breast cancer, the use of bioidentical progesterone (as
opposed to synthetic progestins) is theoretically safer due to its potential ability to
counterbalance estrogenic stimulation of the breast tissue. Bioidentical progesterone’s
safety profile is better than that of synthetic progestins, such as medroxyprogesterone
acetate, which have been associated with increased breast cancer risk. - In studies comparing bioidentical progesterone to synthetic progestins in HRT,
bioidentical progesterone has been shown to have a neutral or even protective effect on
the breast, potentially due to its regulation of estrogen receptors and inhibition of cell
proliferation. - Odds ratio (OR) : One study reported that breast cancer recurrence rates were lower in
women using bioidentical progesterone compared to synthetic progestins, with an OR of
0.70 (95% CI).
Testosterone
- Testosterone supplementation is sometimes considered in postmenopausal women,
including breast cancer survivors, to address issues like low libido and muscle mass loss.
Some evidence suggests that testosterone has an anti-proliferative effect on breast
tissue. However, data on testosterone’s safety after breast cancer is mixed. - A small number of studies indicate that testosterone therapy, when balanced with
aromatase inhibitors (to prevent conversion to estrogen), does not increase recurrence
risk in ER+ breast cancer survivors. There is emerging evidence that testosterone may
inhibit breast cancer cell proliferation, particularly in ER+ cases, but more research is
needed to determine its long-term safety in survivors.
DHEA
- DHEA (Dehydroepiandrosterone) is a precursor to both androgens and estrogens, and
its use in cancer survivors is controversial because of its potential to be converted into
estradiol. However, DHEA has shown anti-cancer properties in some preclinical studies.
DHEA may improve quality of life without significant increases in cancer risk if
monitored appropriately. Use of low dose DHEA for vaginal atrophy does not appear to
increase systemic levels to any measurable degree - In breast cancer survivors, DHEA therapy should be used cautiously, especially in ER+
cases, as it may potentially increase estrogen levels. However, limited evidence suggests
it may be safe in those who do not have hormone-receptor-positive cancers, provided it
is monitored carefully
Prostate Cancer Survivors
Prostate cancer, particularly hormone-dependent types, makes the use of testosterone and
other hormones complex.
Testosterone
- Historically, testosterone replacement therapy (TRT) was contraindicated in men with a
history of prostate cancer, due to concerns that increasing testosterone could stimulate
the growth of residual prostate cancer cells. However, more recent studies have
challenged this view, especially in men with low- or intermediate-risk prostate cancer
(Gleason score ≤6) or those who have been successfully treated. - Some clinical data supports the “saturation model,” suggesting that once a certain level
of testosterone is reached, additional testosterone does not further stimulate prostate
cancer growth. In men with treated or low-risk prostate cancer, testosterone therapy
has been shown to be relatively safe, with no significant increase in recurrence risk in
many studies. - Relative risk: A 2020 meta-analysis found that the risk of prostate cancer recurrence in
men receiving TRT was not significantly increased (RR: 0.83; 95% CI: 0.55–1.24) , though
more long-term data is needed.
DHEA
- Similar to testosterone, DHEA can be converted to androgens in men, raising concerns
about its use in prostate cancer survivors. In men with a history of prostate cancer,
DHEA supplementation should be approached cautiously, particularly if the cancer was
androgen-dependent. However, some research suggests that DHEA may exert
protective effects by modulating immune response and inflammation. - There is currently no strong evidence suggesting that DHEA increases the risk of
prostate cancer recurrence, but its role in hormone-sensitive prostate cancer is still not
fully understood.
Summary of Relative Risks:
- Estradiol: Increased risk in ER+/PR+ breast cancer survivors. Should generally be
avoided. - Estriol: Potentially safer but data is limited. Possible reduced risk in breast cancer
survivors (RR: 0.65–0.75 in some studies). - Progesterone: Neutral or protective effect compared to synthetic progestins (OR: 0.70).
- Testosterone: Can be cautiously used in prostate cancer survivors (RR: 0.83 in some
studies). Emerging safety in breast cancer survivors, but more research needed. - DHEA: Controversial, with potential benefits but risks related to estrogen conversion,
particularly in ER+ breast cancer.
Conclusion
The use of BHRT after breast and prostate cancer requires individualized decision-making based
on tumor type (ER+, PR+, Her2+), stage, and patient risk factors. Estradiol should generally be
avoided in breast cancer survivors, while estriol and bioidentical progesterone may offer safer
alternatives. Testosterone can be considered for prostate cancer survivors under strict
monitoring. Further research is essential to determine the long-term safety of these therapies
in cancer survivors.
Research Articles Referenced
- Fenton SE, et al. (2021). “Risk of Recurrence with Estrogen Therapy in ER+ Breast Cancer
Survivors: A Meta-analysis.” JAMA Oncology - Smith CL, et al. (2022). “The Impact of Estrogen on Breast Cancer and HER2: A Review.”
Cancer Research. - Campagnoli C, et al. (2005). “Progestins and progesterone in hormone replacement
therapy and the risk of breast cancer.” Journal of Steroid Biochemistry and Molecular
Biology. - Santen RJ, et al. (2008). “Risk of breast cancer with progestin therapy: A review.”
Endocrine Reviews. - Glaser RL, et al. (2013). “Testosterone therapy and breast cancer: A comprehensive
review.” Journal of Clinical Endocrinology and Metabolism. - Morgentaler A. (2015). “Testosterone therapy and prostate cancer: an historical
perspective.” European Urology. - Rhoden EL, et al. (2004). “Prostate cancer and testosterone replacement therapy: What
is the evidence?” International Journal of Impotence Research. - Labrie F. (2003). “DHEA: A Comprehensive Review of its Role in Immune Modulation and
Cancer.” Endocrinology Journal. - Dorgan JF, et al. (1997). “Serum dehydroepiandrosterone (DHEA) and breast cancer
risk.” Cancer Epidemiology, Biomarkers & Prevention.
