Combined Therapy Causes Disease

The solution of the drug industry to endometrial cancer of the uterus was “combined therapy.” Combined therapy involved coupling estrogen with progesterone. Before the 1980's, women were prescribed primarily estrogen only. This caused a lack of hormonal balance because estrogen alone over stimulated the lining of the uterus causing uncontrolled growth. This hyper stimulation, in turn, resulted in a condition known as “hyperplasia.” To avoid this risk, progestins were given, to induce menses. Bleeding allowed the endometrial lining of the uterus to shed and brought the otherwise uncontrolled growth somewhat under control, due to a balance of the progestins "opposing" the estrogen.

Progestin was added to protect against UTERINE CANCER. However, the role of progestin and estrogen concerning BREAST CANCER were untested and unclear. As early as 1980, independent studies suggested a causal connection between HT and breast cancer.⁴ Unfortunately for the women taking these drugs, the warning signs went largely unheeded by the drug companies.

The form of progestin used in most combined therapies, starting in the 1980's after the disaster of endometrial cancer, was Medroxyprogesterone acetate (MPA). MPA is contained in many of the drugs sold by the drug companies as the "opposition" to estrogen supposedly needed to avoid uterine cancer. Provera® (manufacturered by Pharmacia / Upjohn / Pfizer), Cycrin® (Wyeth), and Prempro® (Wyeth) contain MPA.

Other drug companies made a generic form of MPA in order to capture a share of the HT market. Although MPA was combined with estrogen to supposedly protect against uterine cancer, it has been used for years to induce breast cancer in laboratory animals for the purpose of studying breast cancer and its treatments. Moreover, progesterone has just been recognized by the World Health Organization ("WHO"), International Agency for Research on Cancer ("IARC"), as a known human carcinogen. The IARC's recognition was made on the basis of studies of laboratory animals that have been known for decades.⁵

Importantly, this HT combination of known carcinogens, after sales of "monotherapy" or "unopposed" estrogen alone were destroyed by the risk of uterine cancer, began without any safety studies or "clinical trials." Clinical trial is explained by Reference Manual on Scientific Evidence, 2nd at 338:

To determine whether an agent is related to the risk of developing a certain disease or an adverse health outcome, we might ideally want to conduct an experimental study in which the subjects would be randomly assigned to one of experimental study in which the subjects would be randomly assigned to one of two groups: one group exposed to the agent of interest and the other not exposed. After a period of time, the study participants in both groups would be evaluated for development of the disease. This type of study, called a randomized trial, clinical trial, or true experiment, is considered the gold standard for determining the relationship of an agent to a disease or health outcome. Such a determining study design is often used to evaluate new drugs or medical treatments and is the best way to ensure that any observed difference between the two groups in outcome is likely to be the result of exposure to the drug or medical treatment.

(Emphasis Added.)

New drugs in the United States, at least in the recent past, generally have been proven to be safe and effective through clinical trials. The FDA can typically refuse a New Drug Application ("NDA") if that drug is not supported by "adequate and well controlled investigations." Clinical trials seem to be contemplated as the "gold standard" defined by FDA Regulations as the proof generally needed for safety and efficacy.

Until July, 2002, combination HT had never been subjected to the "gold standard" required of almost all modern medications. In other words, no one had tested these drugs in clinical trials for safety and efficacy prior to giving them to millions of women. As of July, 2002, 38% of American women used HT.⁶ Forty-six (46) million prescriptions were written for Premarin® in the year 2000 with more than $1 Billion in sales to its manufacturer.⁷ In addition, "... 22.3 million prescriptions were written for Prempro® (conjugated estrogens plus medroxyprogesterone acteate)."⁸ "Since the mid-1980's, combined estrogen/progestin use [had] steadily increased." ⁹

As stated in the accompanying editorial that appeared in JAMA on the date the initial findings of the WHI were published: "…the whole purpose of healthy women taking long-term estrogen/progestin therapy is to preserve health and prevent disease. The results of this study [WHI] provide strong evidence that the opposite is happening for important aspects of women's health…." ¹⁰