Dr. Sima Aidun N.M.D. is a Naturopathic Doctor offering holistic, natural, integrative care to women of all ages. Her main focus is using Bioidentical Hormone Replacement Therapy for perimenopause and menopause. Her Office is located in Scottsdale, Arizona. She also serves Gilbert, Mesa, Tempe, chandler, Cave Creek, Deer Valley, Care free, Fountain hills, and Phoenix area.

HORMONES & RESEARCH

Introduction

The topic of Hormone Replacement Therapy has been the focus of debate both within professional circles as well as among the lay population since its inception. Over time, this debate has received varying degrees of public attention. At times the coverage has been wide enough to create some controversy. On 01/15/2009 Oprah (www.oprah.com) had her first program in the series of bio-identical hormones. In the typical aftermath of such broadcasts we, as practitioners of women’s health, get large numbers of calls and e-mails regarding the topic asking our view. I decided to dedicate a section to this topic, dissect the issue from an objective research-based angle in an attempt to facilitate a better understanding of HRT among my patients. Walking you through the history of research in the field of HRT from 1998 to the present requires a somewhat more explanatory format. If you are concerned and genuinely interested in improving your understanding of this issue, I greatly recommend that you take your time and read this important information.

Let’s start with the Women’s Health Initiative, the study that proved to be pivotal point in medical approach to HRT.

Discussion

What is Women's Health Initiative WHI?

The NIH (National Institute of Health) initiated the WHI in 1991 as a series of clinical trials followed up with observational studies. The original program was to be a 15 year effort involving well over 160,000 generally healthy postmenopausal women. WHI was launched in an effort to better understand and ultimately address the diseases that are the major causes of death, disability, and frailty among postmenopausal women, diseases such as Heart Disease, Breast and Colorectal Cancer, and Osteoporosis. WHI was conducted as multiple and sometimes concurrent branches, each focusing on a specific aspect of the diseases. One of these branches focused on the effects of Estrogen (Premarin) plus Progestin (Important Note:Progestin is not the same thing as Progesterone, a closer look at this difference will be presented later on in this article) on heart disease and hip fractures as well as associated change in risk of breast and colorectal cancer. The WHI Estrogen(Premarin) + P( Progestin) trial was included in light of previous studies that suggested hormone therapy reduces heart disease.

How was the study designed?

The particular branch focusing on Estrogen (Premarin) + P( Progestin) was a type of study employing a design called a “Randomized , Double blind, Placebo study” - subjects were randomly assigned to one of two groups, one group receiving Estrogen (Premarin) plus Progestin, and the other group receiving a placebo, furthermore, during the trial, neither the women nor the medical staff were aware of which type of pill the participants were taking thus both side were blind to any expectations. The 16,608 participants in this part of the study were healthy, active postmenopausal women ages 50 to 79 who had an intact uterus.

What was the outcome of the Estrogen(Premarin) + P( Progestin) study?

While the original plan called for a long duration of clinical study, the effort was halted after a few years of follow-ups based on results which indicated an increase in the incidence of breast cancer, heart attack, stroke, as well as blood clots among the women who were given the hormones as compared to the “placebo” group - after a period of almost 5 years, some 245 of the 8,506 women on Estrogen (Premarin)+P( Progestin), whereas 185 of the 8,102 women on placebo developed breast cancer. This difference was statistically significant enough to warrant the abrupt halt of that branch of the study in July 2002.

After 2002………….

After the termination of the Estrogen (Premarin) + P( Progestin) arm of WHI, observational studies pertaining to this arm of the study continue. Very often, the information we hear sporadically in the news media is gleaned from the preliminary data obtained from these observational studies. Data for the 3 year post study follow up is available on 95% of the women who participated in the original study.

This data indicates that women who took hormone replacement therapy (HRT) during the study continue to be at higher risk of breast cancer three years after the trial was stopped as compared to those who took placebo. Higher risks of cardiovascular events (heart disease, stroke, and blood clots) seen in those taking the Hormone replacement therapy abated in the follow-up period, however, as did the beneficial effects of HRT on bone strength and colon cancer.

A new paradigm :

Regardless of the results of studies on hormone replacement therapy, much less was discussed about Progestin or the Estrogen plus Progestin combination. For example, Progestins appear to counter Estrogen's effects in certain tissues such as the uterus, but may enhance the effects in other tissues such as the breast and bone.

Are there any differences between “Progesterone” and “Progestin”?

Yes. While both Progesterone and Progestin belong to the same family of hormones called Progestogens, there is at least one key difference between the two which has been shown to be detrimental to the nature of their affect on the body : Progesterone is the bio-identical form while Progestin is non bio-identical to the natural Progesterone produced by the human ovaries and adrenal glands.

A review of data available from the many studies comparing the effects of these two hormones on both human and animal subjects shows that their effects differ in some quite important ways. For example, as mentioned earlier, Progestin appears to counter Estrogen's effects in certain tissue such as the uterus, but may enhance the effects in other tissue such as the breast and bone.

Would such fundamental differences have led to alternate results from studies such as WHI depending on the type of the Progestogen (Progesterone or Progestin) used? One major area where there exists a significant difference between these two hormones is in the way they effect breast tissue proliferation and as we shall see, it would be logical to expect these two to carry different risk for breast cancer.

How different is the effect of Progesterone vs Progestin on breast tissue?

Breast cells are subject to ongoing cell division due to constant exposure to Estrogen. During the process of cell division, DNA inside the breast cell can become damaged. Damaged cells have the capacity to become precancerous and eventually cancerous. But nature has its own tried and true solution for this problem, it is called Apoptosis. Apoptosis or “programmed cell death” is the key mechanism by which the body is rid of cells with damaged DNA thus preventing the process of precancerous/ cancerous cell development.

Progestin has been found to prevent apoptosis in some unhealthy breast cells while the opposite has been found to be the case with Progesterone which appears to even promote programmed cell death thus allowing the elimination of cells with the likelihood of becoming cancerous. Progestins also promote the conversion of weaker Estrogens into more potent Estrogens, thereby contributing to their cancer producing potential. Progesterone on the other hand appears to have an opposite influence, creating Estrogens with much reduced potency.

A number of studies have been conducted with the specific aim of identifying the difference in quality, character as well as mechanism of action between Progesterone and Progestin. The following are a sampling of such studies with specific focus on the risk of breast cancer with non bio-identical Progestin:

1.Colditz et al from one of the Nurses’ Health Study’s data, concluded that compared with women who never used hormones, those who used Estrogen alone during their 50’s, increased the risk of breast cancer by over 20%. The same study also found that the addition of Progestin to Estrogen resulted in almost tripling of the risk for breast cancer to over 60%.

2.Newcomb et al studied the risk for breast cancer in large groups of postmenopausal women aged 50-79 years. They found a statistically significant increase in breast cancer of 2% per year for an Estrogen only group, and a 4% per year increase if a synthetic Progestin was used in addition to Estrogen. Use of Progestin only preparation doubled the risk for breast cancer.

Risk of breast cancer with bioidentical Progesterone:

1. Although no randomized, controlled trials were identified that compared the risks for breast cancer between Progesterone and synthetic Progestin, large scale observation studies in humans do show significant differences. In one such observational study in 2007, Fournier et al reported an association between various forms of HRT and the incidence of breast cancer in large number of postmenopausal women who were followed for more than 8 post menopausal years. Compared with women who had never used any HRT, women who used Estrogen only had a non significant increase of 1.29 times the risk for breast cancer. If a synthetic Progestin was used in combination with Estrogen, the risk for breast cancer increased significantly to 1.69 times that for control.

2.In another study done by Fournier, analysis of another group of postmenopausal women indicated the risk for breast cancer was increased significantly when synthetic Progestin was used, but was reduced if Progesterone was used instead.

Putting it all together:

I have cited several studies in this article and there are many more studies providing data that support the same conclusion - adding Progestin, the non-bio-identical form of Progesterone, seems to be a key factor in the rising risk of breast cancer. However, much more data is still needed . Until we can have large scale randomized controlled study like what was done in WHI, the above statement is just an justified educated hypothesis.

“To take advantage of these benefits (bone health, symptom relief etc), you first have to give up the notion that there is an easy, “one size fits all” solution. There isn’t. Some women need or want HRT, some don’t. Some need to use it for only a year or two some will want to stay on it longer. When it comes to hormone replacement, the science we look to for answers is inconsistent at best, influenced by market forces, and confusing to researchers, doctors, and patients alike. The blessing is that this dilemma forces us to tune in more fully to our inner wisdom and to make our choices in full partnership with our intuition and intellect. This approach is the essence of feminine wisdom. “

Christiane Northrup, M.D. - “wisdom of menopause” (http://www.drnorthrup.com/)

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