To HRT or Not to HRT?

You may be hearing a lot of buzz about HRT, and wondering why, given it got such a bad rap 40 years ago, it is now making a come-back. If you are currently asking yourself this question, you are not alone. It is helpful to understand the history and evolution of HRT over the last few decades.

Hormone replacement therapy (HRT) most commonly refers to the supplementation of estrogen and progesterone—the female sex hormones that decline significantly during menopause.

Early Estrogen Sources

While HRT was widely prescribed in the 1970s and 1980s, the early formulations on the market primarily relied on estrogen derived from pregnant mare’s urine (hence the name “Premarin”) and synthetic progesterones known as progestins.

Some smart chemists realised that pregnant mares’ urine provided a lot of estrogens. Although the estrogen metabolites in a pregnant mare’s urine are biologically identical for the horse, they are not bio-identical to humans. Ultimately, a horse’s urinary output is not the optimal input for women’s health!

Natural Progesterone vs. Synthetic Progestins

Natural progesterone and synthetic progestins both fall under the biochemical umbrella of progestogens. However, progestins exert a very different effect on the body than natural progesterone. While natural progesterone supports pregnancy, synthetic progestins prevent it. They are designed to alter the reproductive cycle and are commonly used in birth control pills and other forms of contraception, such as some IUDs and Depo-Provera.

Early formulations of birth control pills containing progestins were found to promote breast cancer in animal studies, leading to subsequent dosage reductions. Unfortunately, the critical distinction between natural and synthetic progesterone-like molecules was not well understood. It is still often overlooked by manufacturers, and sometimes by conventional physicians and endocrinologists. Even today It is not uncommon to see these terms used interchangeably, and to see natural progesterone mislabeled as progestin or vice versa. If the medical community exhibits confusion on this topic, patients can hardly be expected to navigate it easily.

Fortunately these days most prescribers recognise that progesterone is the preferred form, and it is readily available and more accessible.

The Evolution of HRT Safety

Clinical trials on early forms of HRT demonstrated that they successfully reduced menopausal symptoms. A large-scale trial, The Women’s Health Initiative, was launched in the 1990’s, to evaluate the long-term safety of the predominant HRT in use at the time: Premarin and progestins. This was the trial that was halted prematurely due to alarming results showing increased risks of cardiovascular problems, blood clots, strokes and breast cancer. Almost overnight HRT acquired a very negative reputation. After several decades of further research, we now better understand the many flaws in the WHI study, and much more about the risks of synthetic progestins. More recent research shows that the use of human identical hormones can actually benefit cardiovascular and bone heath, as well as helping to maintain healthy cognition.

Part of the reason synthetic substances were initially favoured is that natural substances cannot be patented. Pharmaceutical companies rely on an exclusive patent window to recoup the substantial costs of clinical trials, and to secure a return on their investment before cheaper generic competitors enter the market. While human-identical hormones (often called bioidentical or BHRT) have always been available, they previously required custom compounding into pills or creams, making them cost-prohibitive for many.

Although manufactured in a laboratory, human-identical estrogen is derived from soybeans, and progesterone is made from substances found in wild yams. Their final molecular structures are exact replicas of the hormones naturally produced by the human body, rather than synthetic approximations. Naturopathic doctors have long advocated for these human-identical forms to support health. However, because some synthetic products are still on the market, consumers must remain discerning.

A major breakthrough occurred when a pharmaceutical company developed a way to patent a pill containing natural progesterone (oral micronized progesterone) by patenting its unique delivery mechanism. A similar innovation now applies to human-identical estrogen delivered via transdermal patches or creams. As a result, safe HRT options have come to the forefront of women's health, and an increasing number of patients are inquiring about them.

The safety profile of HRT for menopausal women is now a lot better. Our next SHINE Health Post will tell you more details to consider in a woman’s decision-making about whether or not to use HRT.