In the last 10 years, the dose of estrogen in traditional hormone replacement therapy (HRT) has decreased dramatically. The progestogen (the class of hormones including progesterone) component of HRT has not changed in dose so much as in the quality of the hormone available. If you are using the more commonly prescribed HRT medications today, it is very likely you are:
- Taking a much lower dose of hormone than in the past.
- Taking a bioidentical hormone medication.
- Using a patch, cream, or spray to deliver this hormone to your system.
Lower doses of HRT have been shown to carry less breast cancer and clotting risks than their original counterparts. So, how did researchers decide on the dose of hormone to use in the original trials? How much less hormone are you taking now with the newer medications?
How was the original HRT dose determined for the WHI? What did we learn?
Even early doses of HRT were significantly less hormone than could be found in an oral birth control pill. However, these early doses still represent more hormone than is currently used for HRT today. The original dose of HRT used in the Women’s Health Initiative trials (WHI) was derived to provide the optimal osteoporosis protection. The estrogen used was called Premarin ® This name comes from PREgnant MARes’ urINe. These are non-bioidentical estrogens from horse urine (also known as conjugated equine estrogens [CEE]). They are quite potent estrogens. Originally in HRT prescribing there was no real concern about cardiovascular risk (in fact improved heart health in women taking HRT was anticipated), and while there was some suspected breast cancer risk, it was not assumed to be as significant as it turned out to be. Therefore when estrogen and progestin doses were established for the WHI:
- Osteoporosis risk was the top priority.
- Menopausal symptom relief also ranked high on the list.
- Suspected cardiovascular benefit was also included in the decision process.
The choice of progestin dose was made only for the purpose of balancing estrogens in the uterus to avoid cancer of the endometrium. At that time there were no distinctions made between different sources of progestogens (the class of hormones that includes progesterone and synthetic progestins) and it was thought that variants in this class should be relatively similar. Therefore, the widely available medroxyprogesterone acetate (MPA) was chosen. The actual dosage used in the WHI trials was 0.625mg of CEE and 2.5mg of MPA. Since that time it has been noted that breast cancer risk and clotting risk of HRT are reduced with lower doses of HRT used transdermally. Additionally, the cardiovascular risk of the higher dose oral hormones used in the WHI actually transforms into cardiovascular BENEFITS with lower dose, transdermal HRT in younger women taking a better progestogen.
What has changed?
Since the poor results from the WHI on the hormones listed above, bioidentical estradiol has become preferred by most providers, both conventional and alternative. The oral dose of estradiol in newer HRT prescriptions is about half of the equivalent dose of estrogens used in the WHI. More exciting, however, the dosing of transdermal estradiol preparations is just a small fraction of the oral dose of the original estrogens used in the WHI. They even have a name for these new low doses. They are called “ultra low dose estrogen replacement therapy.” If 0.625mg of CEE was used in the WHI, current transdermal estradiol systems can deliver as little as 0.025mg a day. Vaginal preparations deliver even less hormone with excellent symptom relief. All of it bypasses the liver. This is a huge difference. In terms of progestogens, the quality of these hormones has improved so drastically, no real dose equivalents can even be made. The now routine use of bioidentical progesterone here is a significant step forward regardless of dose. If there is one thing that can’t be stressed enough it is this: medroxyprogesterone acetate should be avoided in routine HRT prescribing. It carries substantial risk. Natural progesterone, if available and tolerated well, performs so differently it is not a fair comparison.
Summary of HRT dose:
- While WHI doses of hormones are now considered high, they were still lower doses of hormones than could be found in birth control pills
- Bioidentical estradiol tends to be the estrogen of choice in current HRT. This is used most preferably in a transdermal patch or cream at a fraction of the dose used in the WHI. These decreased doses do not compromise symptom relief and provide significant reductions in risk from HRT.
- The progesterone component of HRT has changed so drastically it now has nothing to do with dose, but the quality of the hormone used. New generation progestins and, most importantly, natural progesterone have completely changed the face of combination HRT (estrogen + a progestogen).
