The Hormone Controversy: A Brief History

As many of you are aware, there is quite the controversy around hormone therapy…at least in the media. So where did it all stem from?
Well, back in 2002 there was a large study called the Women’s Health Initiative that was published in a major medical journal called JAMA. In summary, the study identified adverse effects of hormone therapy in one of the test groups.
It was a randomized controlled study of women between the ages of 50 and 79 divided into two groups: 1) postmenopausal women with a uterus and 2) those with a prior hysterectomy.
The women with a uterus were randomized given either Prempro {Premarin 0.625mg + Medroxyprogestoerone} or a placebo. Those in the hysterectomy group were randomized to receive either Premarin 0.625 mg or a placebo.
Before we dive into the results, it’s first important to understand more about the drugs administered:
Premarin is a drug that is created by extracting several horse estrogens from a pregnant mare’s urine. As you might imagine, this is a very different compound than human estrogen (note: human estrogens are estradiol, estrone, and estriol). Another thing to consider is that Premarin was given orally in pill form. We’ll get into the difference between oral vs. non-oral hormones later on.
Medroxyprogesterone Acetate {MPA} is a synthetic progestin. It’s similar in chemical structure to natural progesterone but very different in its actions in the body other than in the uterus. Both MPA and progesterone protect the uterus from proliferative effects of estrogen.

Group 1: Still has a uterus (Premarin + MPA) Group 2: Hysterectomy (Premarin Only)

Coronary Heart Disease: Increased risk with hormones

Coronary Heart Disease: No statistical difference
Stroke: Increased risk with hormones Stroke: Small, but increased risk with hormones
Fracture: Decreased risk with hormones Fracture: Decreased risk with hormones
Breast Cancer: Increased risk with hormones Breast Cancer: No statistical difference
Blood Clots: Increased risk Blood Clots: Increased risk with hormones
Colon Cancer: Decreased risk with hormones

Colon Cancer: No statistical difference

After 5+ years of follow up, it was determined that the risks outweighed the benefits for those postmenopausal women with a uterus. The trial for that group ended while the hysterectomy test group continued. Once these results hit the media it didn’t take long for everyone to freak out and abandon their hormone treatments.
The problem with the media in response to this study was that it grouped all hormone treatments into one “dangerous” group. Even in medical journals, you have to really dig deep to understand which hormones were used, how they were administered, etc. In an effort to even the playing field, here are some studies that show the positive impacts that bioidentical hormone therapy (BHT) can have when implemented appropriately.

  • The safety and efficacy of bioidentical hormones for the management of menopause and related health risks. The studies suggest bioidentical progesterone does not have a negative effect on blood lipids or vasculature as do many synthetic progestins, and may carry less risk with respect to breast cancer incidence. Studies of both bioidentical estrogens and progesterone suggest a reduced risk of blood clots compared to non-bioidentical preparations. Bioidentical hormone preparations have demonstrated effectiveness in addressing menopausal symptoms.
  • Bioidentical menopausal hormone therapy: Registered hormones are optimal. Menopausal hormone therapy (MHT) continuously combining oral micronized progesterone with transdermal estradiol can presently be considered as the optimal MHT. It is not only safer than custom-compounded bioidentical hormones, but it is also safer than oral conventional MHT and has the best breast profile.
  • The bioidentical hormone debate: are bioidentical hormones safer? Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT.
  • Hormone replacement therapy in menopausal women: Past problems and future possibilities. Transdermal administered estradiol has been shown to be an efficacious treatment for hot flushes possibly without the increase in blood clotting that is associated with administration of oral CEE. Further, natural progesterone may have a more beneficial spectrum of physiological effects than synthetic progestins.
  • What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone. Unlike oral estrogens, transdermal estradiol has been shown not to increase the risk of venous thromboembolism (VTE), or stroke (doses ≤ 50 μg), and to confer a significantly lower risk for gallbladder disease. Unlike some progestogens, progesterone is also not associated with an increased risk of VTE or with an increased risk of breast cancer.

As you can probably see, the major drawback of bioidentical hormones is the lack of all-encompassing research. If you’re waiting around for the next significant trial (a randomized placebo controlled trial) around safer forms of hormone therapy, unfortunately I don’t think it will be anytime soon. The 2002 Women’s Health Initiative study was a multi-million-dollar initiative backed by a huge pharmaceutical company {Wyeth}. It took over 60 years from when Premarin came on the market until this randomized controlled study was done.
For now, the best thing you can do is work with a provider who completes advanced education and reads the research we do have to determine a treatment plan that is designed specifically to meet your needs.
At Amy Brenner, MD & Associates we stand behind hormone therapy as an effective treatment. That is, as long as it is administered properly. Whenever recommending hormones to a new patient, we stick to a plan that we call the The Four R’s
Right Hormone: First and foremost, we would never give a patient horse estrogens or synthetic progestin. We only give bioidentical hormones, meaning they have the same chemical structure as human hormones.
Right Route: Because oral estrogens are metabolized in the liver they increase the risk of clotting. This is why all of our hormones are administered via creams, pellets or injections, allowing us to bypass any issues with the liver.
Right Dose: Some studies have shown risks with excess estrogen. The same goes for testosterone and progesterone. Because of this, we monitor for side effects and check levels on a frequent basis.
Right Combo: With every treatment, it’s our goal to create a balanced hormonal symphony which could involve the thyroid, insulin, adrenals, Vitamin D, and more.
If you have symptoms such as decreased energy, insomnia, hot flashes, or a low libido that could be resolved with hormone optimization, be sure to give us a call. We’ll help you break through the noise and find a program that’s tailored to you.