For years, since the 1950’s, hormone therapy had been used in women for menopausal symptoms, such as hot flashes, mood changes, vaginal atrophy, etc. Physicians observed that women lived longer than men when they did this. In addition, women had less heart disease before menopause than did men and this was thought to be due to the high amounts of natural estrogen present premenopausally.

 

This preventive action of estrogen was thought so important that a huge study was organized to evaluate this, called the WHI study, or Women’s Health Initiative.[1]Here, a large number of women (16,608) were split into three groups. One group took estrogen alone (Premarin was used), one took the combination estrogen plus medoxyprogesterone (Prempro), and one group was the control group who just used placebos (sugar tablets).

After five years, they had to stop one part of the study because the Prempro group had an increased risk of breast cancer. There were 8 more cases of breast cancer per 10,000 women years in the Prempro group vs the placebo group. Unfortunately, this hit the news and was hyped and blown out of proportion, so many women got scared and discontinued the use of their HRT.

However, what the news didn’t say is that those on the Premarin alone did not have an increased risk of breasts cancer, they had the same risk as those taking placebo. There were actually 5 less cases of breast cancer in the Premarin alone group vs the placebo group. But you didn’t hear that much in the news. Unfortunately, two years later many of these women were found to have developed osteoporosis, a problem that could have been prevented by estrogen if they had continued to take them.

 

Development of Hormone Pellet Therapy

Because of the negative press from the WHI study, physicians searched for a method to administer hormones without an increased risk of breast cancer, or other problems. We knew that estradiol alone did not increase the risk from the WHI study, so we continued use of this hormone. However, taken orally it increased the risk of stroke. In the WHI study, there were 9 more cases of stroke per 10,000 women years. So how are we to administer this without increasing risks?

The answer was to administer estradiol transdermally. We soon learned that administering estradiol transdermally, or through the skin did not increase the risk of developing breast cancer. This now is the recommended by many experts in the field to avoid this potential complication of estradiol.[1]With the transdermal route, women can now reap the benefits of hormone therapy, such as prevention from osteoporosis, while not exposing them to increased risks of breast cancer or stroke.

 

A method that developed partly because of this need for a good transdermal route was hormone pellet therapy. Here, hormones are inserted below the skin (after anesthetizing the skin) and fulfilled the need for a safer transdermal method of delivering hormones. In addition, testosterone could also be administered at the same time, which improved the woman’s libido, energy level, thought process, and well-being.

The Dayton Study

A recent study unexpectedly demonstrated a new potential benefit of hormone pellet therapy. This study, done in Dayton, Ohio by Glaser and Dimitrakakis[1]called the Dayton Study, demonstrated a remarkably decreased risk of breast cancer when testosterone pellets plus an aromatase inhibitor were used. Aromatase inhibitors help prevent the natural metabolism of testosterone to estradiol, resulting in a better balance of testosterone and estrogen.  They started with 1268 women in 2008 and ended up with 5642 women in 2013. Over that time, there were 8 cases of breast cancer for an incidence of 142 cases/100,000 person-years. Matched controls who did not take testosterone had an incidence of 293 cases/100,000, consistent with other study’s placebo group.

This equates to a 50% reduced risk of developing breast cancer. Moreover, in women who were adherent to the testosterone pellet therapy, the breast cancer risk was 73 cases/100,000, a whopping 75% reduction in risk of developing breast cancer. Adherence simply means they stuck with doing the therapy every 3 months and didn’t allow any lapse of time when they would not have any testosterone inside them for months at a time.

Moreover, the patients were referred to the Dayton Study due to complaints that were common with hormone therapy. These included hot flashes, sweating, sleep disturbances, heart discomfort, depressive mood, irritability, anxiety, pre-menstrual syndrome, fatigue, memory loss, menstrual or migraine headaches, vaginal dryness, sexual problems, urinary symptoms including incontinence, musculoskeletal pain and bone loss. Not only were most of these symptoms relieved or treated by the hormone pellet therapy in over 95% of the patients, but the patients also experienced the decrease in breast cancer incidence. What a great double whammy! The authors even suggested that further studies should be done on women using pellet therapy for the possible prevention and therapy of breast cancer.

The Continued WHI Study

Another study showed even more interesting results. Many of the women in the original WHI study liked the hormones and wanted to continue taking them, especially those in the estrogen alone group that didn’t show an increased risk of breast cancer. Thus, from 2002 to the present, they continued taking them. They probably said, “Don’t take my hormones away!” because they felt good on them.

 

Ten years later, in 2012, an updated article on the WHI was published.  The News, unfortunately, didn’t hype this so most people did not hear about the results of this study, but they are an eye-opener. The researchers were able to follow 7645 of women (78% of the original study) who continued to take estrogen along with or without medroxyprogesterone.

 

Shockingly, the researchers discovered that women who had continued the estrogen therapy had a 24% reduced risk of developing invasive breast cancer compared to those who took a placebo during the 12-year follow-up.  In those women who developed breast cancer during those 10 years, those on estogen therapy had a 63% reduction in death from the disease compared to those in the placebo group. In addition, if they stayed on estrogen therapy they had a 39% less chance of dying from all-causes (all-cause mortality).

Let me emphasis this point: if the women continued taking the estrogen, they had much less breast cancer occurring (24% less). If they were unfortunate to develop breast cancer over that 12-year period, those women taking the estrogen had a much less aggressive form of breast cancer and had less risk of dying from it compared to those not taking the estrogen: a 63% reduction in death, from their breast cancer. And, their overall all-cause mortality was less by 39%.

 

In this follow-up study of the WHI, the only group that showed an increase in breast cancer was the group on combined therapy of estrogen and the synthetic progestin, yet this increase was very small. It is very apparent that you should therefore not take the synthetic progestin but do take estrogen because you’ll live longer. Taking estrogen as in natural bioidentical progesterone has not been shown to increase breast cancer, and may even decrease its risk its risk.[1], [2]Thus, if you still have a uterus and must use progesterone, use only the latter bioidentical type of progesterone and not the synthetic progestogens.

 

Birth of Bioidentical Hormone Therapy

Because of the many changes we have seen in hormone therapy over the years, a new concept has risen called Bioidentical Hormone Therapy, or BHT. Here we use the natural hormones of estradiol, progesterone, and testosterone to improve the hormone balance of the women. Hormone pellet therapy is a method to administer BHT and we have found it gives a woman or a man the best results. BHT is discussed in another blog article on TrueMD.