Hormones & Cardiovascular Health

A Transformational Case in Cardiovascular Health and Hormone Therapy

By Greg Wolf, MD

As a physician deeply involved in hormone restoration therapy, I’ve encountered many compelling cases over the years. However, some cases stand out so profoundly that they demand a reexamination of long held medical beliefs. Today, I want to share with you a remarkable story about two remarkable cases—that not only supported my perspective about the healing value of Physiologic Hormone Restoration Therapy (PHRT)® but also transformed the thinking of a quite skeptical and irate cardiologist.

The Patients Who Became an “N of 2”

The year was 2014. Two women, both 58 years old, both former smokers, came to see me under strikingly similar circumstances. Decades earlier, in their late twenties, both had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). Following their surgeries they were placed on Premarin and remained on it for 20 years—until they each suffered an acute coronary syndrome that led to the placement of stents in their coronary arteries.

Following their ACS events their doctors pulled them off hormone therapy, warning them that HRT was dangerous for women with coronary artery disease. What followed was 8 years of misery. Their menopausal symptoms fully returned, and despite discontinuing tobacco, adhering to statin and aspirin therapy, and managing their blood pressure, their heart disease continued to progress. Every two years both women required another coronary artery stent. By the time I met them they each had five stents.

After eight years of feeling poorly, both these women expressed to their cardiologists that they intended to seek out menopausal HRT. Their cardiologists strongly advised them against doing so, warning them that HRT would worsen their already problematic coronary artery disease and increase their risk of MI and stroke. One of the cardiologists even said to his patient that she would visit a hormone doctor “over my dead body.” Despite their heart doctor’s admonishments, they each told their cardiologist that they felt so poorly they were willing to take the supposed risks. Clearly, when they walked into my office, they were desperate to feel better.

Challenging the Paradigm

The fear that estrogen could worsen these patient’s cardiovascular disease was based on a monumentally flawed interpretation of a study published in October 2002 in JAMA known as the Women’s Health Initiative (WHI). The WHI quickly became headline news and immediately altered the medical dogma regarding menopausal HRT.

Many, if not most, physicians practice what I call “headline news medicine.” The headline in this case was simple. Menopausal HRT is bad for women in menopause. Yet, both the actual expansive scientific literature about menopausal hormonal replacement therapy and my clinical experience suggested otherwise. Therefore, I initiated these two patients on PHRT®, a rhythmic method of delivering hormone replacement therapy that mimics a menstruating woman’s natural hormonal cyclicity and balance rather than providing static, non-sequential, non-physiologic, hormone administration.

The results of PHRT® with these two patients were at once remarkable and average. Both women, within weeks, experienced a resurgence of vitality. Their energy returned, their sleep improved, and their overall well-being skyrocketed. They got reacquainted with their sexuality. They hadn’t felt this good in years. However, all this excellent clinical benefit wasn’t the ultimate outcome of this therapy. The real revelation came two years later when they underwent their every two-year routine cardiac reevaluation.

One patient’s nuclear stress test was so good that her cardiologist deemed further testing with coronary angiography unnecessary, something that hadn’t happened previously. The second patient only had a coronary angiogram, and to her cardiologists shocked surprise, the results showed frank improvement in her coronary artery disease.

The Moment That Changed Everything

The cardiologist who had initially opposed hormone therapy so adamantly that he told our patient she would visit me only over his dead body was amazed. He performed the angiogram and that single case demonstrating frank improvement in coronary artery disease—what I call a “transformational N-of-1”—was enough to make him question, properly so, everything he had believed about hormone therapy and heart disease.

As physicians, we too often fall into the trap of thinking medical dogma is fixed and absolute. But cases like these remind us that medicine is an evolving scientific discipline. What we once believed to be dangerous may, in fact, be the very thing that restores health.

Rethinking HRT and Heart Disease

These cases suggest that it’s time to reconsider the widespread avoidance of menopausal hormone therapy—particularly transdermal, rhythmic, bioidentical HRT—in women with coronary artery disease.

We know that estrogen deficiency accelerates atherosclerosis. We also know that stents, in the absence of estrogen, may potentiate arterial neointimal hyperplasia, possibly explaining why both women required additional stents every two years. Additionally, the old fear that HRT could destabilize plaques has never been substantiated in population-based studies.

Evidence from studies of menstruating females suggests that rhythmic estradiol administration with spiking estradiol levels on cycle days 11 and 12 would optimally stimulate the production of endothelial progenitor cells (EPCs), the very stem cells responsible for vascular endothelial repair as well as vasculogenesis, the de novo development of collateral circulation. These studies have demonstrated that the preponderance of EPC’s produced during a menstrual cycle arise during the preovulatory estradiol surge, a process mimicked with PHRT®.

In these two women—both of whom had no uterus—this EPC stimulation was probably even more effective in rehabilitating coronary circulation because those bone marrow derived stem cells which would normally home towards the endometrial lining were now traveling throughout the systemic circulation homing towards tissues which were chemokine-signaling vascular insufficiency or endothelial damage. A doubling of EPCs in the systemic circulation has been observed in hysterectomized mice with retained their ovaries, which is supportive of this thesis.

The Future of Hormone Therapy in Cardiology

The traditional approach to hormone therapy has been cautious, if not outright fearful, when it comes to cardiovascular health. But cases like these compel us to think differently. If Physiologic Hormone Restoration Therapy can reverse coronary artery disease progression, we must ask:

  • Are we doing a disservice to millions of postmenopausal women by denying them appropriate hormone therapy?

  • Should we be using rhythmic, bioidentical, transdermal HRT as a standard approach, rather than the low dose, less adequate, static HRT

  • How many more women could be helped if we shift our understanding of hormones from “risk factors” to “protective agents?”

The answer lies in challenging old paradigms with new science and most importantly, real patient outcomes.

Final Thoughts

I have seen many cases of hormone therapy transforming lives, but this was different. It wasn’t just about symptom relief—it was about measurable, life-saving cardiovascular improvements. These patients defied the expectations of their cardiologists, and in doing so, changed minds in the medical community.

This is the great power of the N of 1, or in this case the N of 2. When a single patient’s story forces us to reconsider what we thought we knew, we are faced with a choice – discount what we observe as an anecdotal outlier or begin to ponder the possibility that what is being revealed should open us to reconsider medical dogma.

I choose the latter.