Hormone replacement therapy (HRT) has long been a cornerstone of managing menopausal symptoms and promoting overall health in women after menopause. However, the traditional approach to HRT—using static, daily doses of estrogen and progesterone—may not be delivering the full spectrum of benefits that women need. This post explores the idea that to truly optimize hormone function after menopause, women might need to return to a more natural, rhythmic hormone cycle, even if it means experiencing a monthly bleed.
As an outsider examining traditional HRT, one might question the rationale behind replacing hormones that naturally cycle in a static, unchanging manner. Bioidentical HRT, which uses compounds identical to those produced naturally by the body, is a step in the right direction, but it still falls short of mimicking the natural rhythms of estrogen and progesterone. The question then arises: if we want to optimize hormone function, why not also replicate the physiological doses and rhythms that existed before menopause?
While the concept of rhythmic HRT is still in its early stages, and the evidence supporting its benefits is limited, the potential advantages are intriguing enough to warrant exploration. When I first introduced this idea to my team—comprising nearly 30 women—I was met with some initial resistance. However, as I explained the potential benefits, the idea gained traction. The most common question we encountered was whether rhythmic, physiological replacement would cause a monthly bleed. The answer is yes. While this may be off-putting to some, many women and healthcare providers who have adopted this approach are willing to accept the inconvenience of a monthly bleed in exchange for the benefits they’ve experienced.
One of the first pieces of evidence that introduced me to the concept of rhythmic HRT was the Danish study, which showed that cyclic combined therapy provided protection against heart attacks, in contrast to the significant increase in heart attack risk observed with continuous, static combined therapy. This study highlighted the importance of cycling progesterone, though it didn’t delve into the specifics of how to cycle the hormone. Further research has supported the physiological benefits of cycling progesterone, particularly in relation to heart health.
Estradiol, a form of estrogen, is well-known for its positive impact on bone health. Bone metabolism leaves a trail of biomarkers that can be tracked, and these markers improve with sufficient estradiol levels. This is why we prioritize its use in our bone health programs. However, the benefits of estradiol and progesterone extend beyond just bone health. These hormones play a crucial role in regulating other systems in the body, and their alternating surges are essential for maintaining overall health.
When discussing rhythmic HRT with patients and colleagues, the first concern that often arises is the risk of breast cancer. This fear persists despite the lack of evidence linking estradiol to an increased risk of breast cancer. In fact, long-term studies suggest that estrogen is protective against breast cancer. The physiological basis for this makes sense—if estrogen were truly causative of breast cancer, we would expect to see more cases before menopause, when estrogen levels are higher, and fewer cases after menopause, when levels decline. Neither of these scenarios holds true, so why assume that more estrogen would increase breast cancer risk?
Breast tissue is known to change in response to varying levels of estrogen and progesterone during the menstrual cycle. Surgical specimens correlated with reported cycle phases and serum hormone levels confirm that breast tissue changes throughout the cycle. These tissue changes are also associated with shifts in genomic expression, particularly in tumor suppressor genes. Clinical evidence supports the idea that a deficiency in progesterone can increase the risk of breast cancer, while surgery performed during the luteal phase, when progesterone levels are higher, tends to have better outcomes.
Although we lack large-scale trials on rhythmic HRT, the available data suggests that cycling hormones could play a protective role in breast health. This is a critical consideration for women weighing the benefits and risks of different HRT approaches.
Cardiovascular health is another area where rhythmic HRT may offer advantages over static dosing. Before menopause, women have lower rates of cardiovascular disease than men, a difference often attributed to higher estrogen levels. However, the exact mechanisms behind this protective effect are not fully understood. One hypothesis involves endothelial progenitor cells (EPCs), which are critical for blood vessel formation and repair. Women typically have higher levels of EPCs than men, and these levels peak during the follicular phase of the menstrual cycle, when estrogen levels are highest. After menopause, EPC levels decline to match those of age-matched men, suggesting that static, low-dose HRT may not adequately reproduce the cardiovascular benefits of natural hormonal cycles.
Hormones like estrogen and progesterone don’t work in isolation; they interact with receptors in tissues throughout the body. These receptors are essential for the hormones to exert their effects, but receptor function can be influenced by the way hormones are administered. Estradiol, for example, increases the density of progesterone and estrogen receptors, while progesterone reduces receptor expression. In a static dosing regimen, these opposing effects are constant, potentially leading to receptor dysfunction and suboptimal outcomes from HRT.
This hypothesis is difficult to study directly, but it underscores the importance of considering hormone receptor dynamics when evaluating the effectiveness of HRT. A randomized trial comparing static and rhythmic dosing could provide valuable insights into how best to optimize hormone replacement.
When we compare HRT for women with testosterone replacement therapy (TRT) for men, the differences are striking. The goal of TRT is to restore testosterone levels to those of a man’s younger self, optimizing his health and well-being. In contrast, women’s HRT often focuses on providing the lowest dose necessary to manage symptoms, rather than aiming for physiologic levels. This discrepancy raises questions about whether women’s HRT could benefit from a similar approach, restoring hormone levels to those seen in premenopausal women.
The historical development of HRT may have contributed to this conservative approach. Early commercial HRT products were synthetic and static, and research on these products set the standard for hormone replacement. However, this standard may not reflect the best baseline for optimizing women’s health. Instead of viewing physiologic dosing as “guilty until proven innocent,” we should consider it a viable option worth exploring.
Currently, there are no large-scale trials on the effects of rhythmic and physiologic dosing of HRT in women. However, the existing evidence suggests that we may be missing out on optimal health benefits by sticking with static, low-dose HRT. Many women who have not done well on traditional HRT could potentially benefit from a more dynamic approach that mimics the natural rhythms of premenopausal hormone cycles.
While not all women may want to experience monthly menstruation after menopause, the potential health benefits of rhythmic HRT should not be overlooked. As more research emerges and more healthcare providers explore this approach, we may see a shift toward more personalized and physiologic hormone replacement strategies.
Your hormone regimen may be failing you because you might need to continue cycling your hormones as you did before menopause. While the idea of returning to a monthly bleed may not appeal to everyone, the potential benefits for bone health, breast health, cardiovascular health, and overall well-being make it an option worth considering. As evidence continues to accumulate and the conversation around HRT evolves, rhythmic dosing could become an important tool in optimizing women’s health after menopause.
For those who are not seeing the benefits they expected from traditional static HRT, it may be time to explore new approaches. By mimicking the natural hormonal rhythms of the premenopausal body, we may be able to achieve better health outcomes and improve the quality of life for countless women.
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Access to proper care and personalized hormone replacement therapy (HRT) is crucial for women to fully benefit from its potential in optimizing health and relieving menopausal symptoms.
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Optimizing hormone replacement therapy (HRT) requires personalized care, regular monitoring, and the right combination of hormones, doses, and delivery methods to achieve the best health outcomes.
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Rhythmic hormone replacement therapy, which mimics natural hormonal cycles, may offer greater health benefits than traditional static dosing, potentially improving outcomes for bone, breast, and cardiovascular health in postmenopausal women.
