What are bio-identical hormones? How are they different than synthetic? And why is there so much controversy about them? It seems that perhaps in the debate of should you or shouldn’t you, we, as the medical professionals, forgot to pass along the physiology behind hormones and menopause. I believe that if you understand the physiology and history of hormones, you can decide for yourself what side of the hormone replacement fence you might want to be on. Prior to 2002, hormones were prescribed rather freely. We believed that increasing hormone levels in nearly all women to be advantageous to letting the hormone levels decline as they naturally do during menopause. Women were predominately prescribed Premarin (conjugated estrogens) or Prempro (conjugated estrogens plus Progestin). This gave relief to symptoms such as hot flashes, night-sweats, insomnia, irritability and depression, and women developed fewer decreases in skin elasticity, vaginal dryness, and physical aging in general. In 2002, this changed with the halt of the Women’s Health Initiative (WHI) study. The WHI was a large-scale study that determined that women on these hormones had an increase in risk for stroke, deep-vein thrombosis, cardiovascular disease, and breast cancer. The results were considered clinically significant enough to halt the study because of the increased danger to the women of the study that were receiving the hormones. The word spread like wildfire, and women across the country were taken off of their hormones (with, for many, the return of those hot flashes, nightsweats, insomnia, irritability and depression, decreased skin elasticity, and vaginal dryness).
With the decrease in the use of conjugated estrogens came a search for a more “natural” approach to hormones and the surge in the use of bio-identicals, hormones compounded by pharmacists that are produced from plant-based sources (primarily yam and soy). The main advantage of the bio-identical versions is that they can be more closely made to look like our naturally occurring estrogens and progesterone (they are a better fitting ‘key’ into our hormone receptors). The question is whether or not this decreases the risks determined in the WHI.
To answer this question, we must first understand the players. There are two major players in the female hormone profile that change during menopause (although the picture is actually more complex): estrogen and progesterone. Although we often talk about estrogen as a single entity, there are actually three main types of estrogens known as estrone (E1), estradiol (E2), and estriol (E3). Many of the hormones that are considered “synthetic” are primarily E2, which is the predominant estrogen in our systems. However, many postulate that E1, or estriol, although found in the body in much lower levels, actually provides a protective effect for the body as a weaker estrogen. It does this by filling some of the receptors that would otherwise be triggered by the harsher E2 (including perhaps some receptors in tissues that lead to the risk factors listed above). The presence of this weaker estrogen in compounded hormones is perhaps another advantage of bio-identicals compared to the synthetics of the WHI.
Perhaps the biggest difference between the hormones used in the WHI and bio-identicals is the use of Progesterone as opposed to either no progesterone to balance the estrogens that are supplemented, or the use of a synthetic progestin (notice the change in spelling). Progestins are structures similar to but not identical to human progesterone that are not recognized well by the body and have been shown to absolutely increase risks. Progestins are rarely used today, with the majority of supplementation coming in the form of the more natural Progesterone. And so, with better fitting keys and better hormonal constituents. should you be on the pro-side of the bio-identical hormone fence? Unfortunately, the answer is not a given even with the proposed benefits from above.
The problem is that although there seem to be advantages, we can’t technically prove that bio-identicals are safer than the hormones of the WHI due to the lack of a large-scale study. Because of this current lack of study, we are forced to assess the benefit and risk ratio on an individual basis as we would for the synthetic versions that we do have studies for. The current consensus (and it is stretching it to even say there is a consensus) in the medical community seems to be to use the lowest doses possible for limited amounts of time, and only for those who are good candidates and suffering from menopausal symptoms.
Hormones are generally contraindicated in those with a history or strong family history of hormone related cancers, and for most, the risks of supplementing hormones (cardiovascular and stroke risk) are assumed to outweigh the benefits after five years of continued usage. Hence, the controversy: do you fall on the side of the fence comfortable with assuming bio-identicals are safer because of the physiology behind them, or are you on the side that wants to wait until the absolute verdict is in? I guide my patients through this question by asking . . .are you suffering? What is your quality of life? Are you sleeping? Many women are comfortable “re-setting” at lower hormone levels, but if you aren’t one of them, you might feel like a risk is worth feeling better.
Many still don’t feel well when trying to taper after the five years. Some just plain don’t want to quit and prefer to take their chances to hold onto the youthful effects of the hormones. These are the questions to ask yourself and your healthcare provider, and the considerations to make. As an educated patient, you are the best person to decide what side of the fence you should be on, but a good practitioner can guide you.