by Dr. Charles Mok
This is an overview of the best practice in medicine for dealing with menopause. On prior blog posts, I’ve shared most of the references so I won’t repeat them here unless there is new information.
Hormone replacement therapy for women entering menopause is pretty much a standard of care in the 80s 90s and early 2000’s. Then the WHI, (Women’s Health Initiative Trial), cast doubt on the safety of artificial hormone drugs. There was a slight increase risk of heart disease and breast cancer in women who were started on hormone replacement 10 to 15 years after the onset of menopause.
About 50% reduction in hormone replacement prescriptions occurred after the findings of the WHI study. But it turns out the initial results of the WHI study were inherently flawed. Instead of a slight increase risk of heart disease in postmenopausal women (when started on synthetic hormone drugs), there was actually a 40% reduction in heart attacks for women who were started on hormone replacement within 10 years of menopause onset. Estrogen was actually cardioprotective.
There been other studies since that time, notably the ELITE study, published in 2016, that show us that the cardiovascular protection from estrogen-only occurs started within 6 to 10 years of onset of menopause. After that time there is no benefit, yet no harm.
With regards to breast cancer, multiple studies in the United States and abroad have shown that the synthetic hormone drugs, such as the horse-based estrogen, Premarin, that we use in the United States, as well is the synthetic drug progestin called Provera are linked to slight increase risks breast cancer. With actual human identical hormones, what people refer to as natural hormones that are commonly available, there is no increased risk. In fact, there is perhaps a slightly reduced risk.
The WHI trial showed a 40% reduction in heart attacks in women who started hormone replacement therapy within 10 years of menopause and continued them long-term. A Danish study, using human estrogen rather than horse estrogen in addition to synthetic progestin found that not only did hormone replacement lower the rate of heart disease, but the longer women were on it, the more protection they had both from their heart disease as well as from all-cause mortality. In the 16 year follow-up of the Danish health study on hormone replacement, women had about a 50% reduction in heart attacks, and over 70% reduction in premature deaths.
The WHI trial, as well as other studies, showed a slight increase risk of breast cancer in women taking synthetic hormone drugs, and neutral or slight protection against breast cancer when taking actual hormones.
But there was a missing link. Testosterone is a dominant hormone in a young healthy woman, about five to twenty times more abundant than estrogen.
In 2004, a study was done in Australia, adding testosterone pellets to standard hormone replacement therapy. In this study, they added testosterone to estrogen and synthetic progestin.
They dosed the testosterone at about 1 mg per pound of body weight. The pellets were inserted under the skin to give long-term release. This was known to have a long-term safety record and give very predictable results. The estrogen chosen was somewhat random. They use both horse synthetic estrogen, as well as human-identical estrogen, estradiol.
They followed the women for about six years, and the average age of the women at the initiation of the study was about 56 years old.
What they found was pretty remarkable. In Australia, at that time, it was estimated that about 380/100,000 woman-years would develop breast cancer. A person-year is a statistical comparison. So we do say the risk is 380 relatively speaking.
For the women on synthetic hormone drugs and testosterone, the breast cancer rate dropped down to 283/100,000 woman years.
And for the women who were not on synthetic progestin, but only estrogen and testosterone the rate of breast cancer fell down even lower to 73/100,000 woman years. An amazing 80% reduction in the expected risk of breast cancer!
Numerous papers have been printed on the subject since that time. Testosterone is used at the dose of about 1 mg per pound of body weight used as a pellet, or an implant. The implants breakdown over about three months and is then repeated. The place through a small incision in the skin. There are no adverse drug events related to testosterone replacement therapy. It has additional benefits such as improved sexuality, improved skin, improved fullness of hair, improved energy and leads to weight loss. Overweight women lost an average of five pounds in six months.
A long-term study performed by researchers in breast cancer as well as members of the national institutes of health initiated a ten-year study initiated 2008. (This means this study still has one year to go). In this study they used testosterone alone in most women, only occasionally adding estrogen. What they found was, over several years, all symptoms of menopause improved. There were no adverse drug events and a 50 to 75% reduction in rates of breast cancer. The reduction in breast cancer rates were based on how long the women were on testosterone replacement. The longer they were on it, the more protection they had. Again, they use the same dosing, about 1 mg per pound as a testosterone pellet.
Hormone replacement therapy has huge implications for both men and women. There is been a significant amount of bias in the medical community, the FDA, and various medical societies. There are some who recommend that men and women just experience “normal aging” and not treat hormone deficiency. But, that would be as absurd as not treating hypertension, diabetes, heart disease, or cancer.
We are talking about a treatment that specifically deals with diseases that are associated with “normal aging.” In both men and women, hormone replacement therapy has been linked to cardiac protection, less cancer, less hypertension, better cardiac lipids, and favorable effects on weight, sexuality, mood, and quality of life.
As a side note, in 2016, a study was published on an evaluation of 83,000 men in the Veterans Administration health system that had low testosterone. About half the men with low testosterone were treated with testosterone replacement, and the other half were not treated. These men were about 66 years on average.
They were followed for six years, and the men testosterone replacement had one-half the death rate, and one-half the amount of heart attacks and strokes. Not to mention that testosterone replacement therapy has a substantially favorable effect on weight maintenance, potentially reversing diabetes, improving quality of life. Yet, the FDA has still not approved testosterone replacement for men with low testosterone unless they have a specific disease to their testicles or the brain, or an extra female chromosome. There is a 50% less chance of dying, more affected than in any other drug. The FDA says it “shouldn’t be used” because of something to treat those conditions. It’s unbelievable but true.
For women entering menopause, or getting symptoms of hormone imbalance, you do have an option. While laboratory evaluation is done, treatment decisions are based more on the clinical findings than the lab. Typically, a woman who still is having periods is put on a testosterone pellet, 1 mg per pound of body weight. And started on progesterone, the natural human type orally.
As she enters menopause, and stop having periods, estrogen level drops. At this point we would add an estrogen pellet. The estrogen pellet be comprised of estriol and estradiol. Generally, about 10 mg, 1/10 the amount of testosterone as this is how the ratio naturally is in your body when you’re much younger.
For women with specific concerns about breast cancer, and at no real risk factor for the potential for heart disease, she may choose to forgo estrogen replacement therapy. Estrogen replacement has been implicated in the development breast cancer, but it turns out we were just wrong. Yet, that does not reduce the bias in the medical community or the public at large.
In that case she can go on just testosterone alone. As studies have shown with over a thousand women for several years, it works just fine for relieving symptoms of menopause, and what reduces the risk of breast cancer by over 50%. While there is no evidence that you get as much cardiac protection, you will get some, but long-term studies, following women for up to 16 years, show over 50% reduction in heart attacks and premature death when estrogen is added.
In cases where women have had a diagnosis of breast cancer and have been treated, the use of estrogen has been controversial. Studies have shown that the recurrence rate is no higher when estrogen is added. However, there still may be fear, and/or bias, against use of estrogen in the setting. In this situation, I would have used testosterone pellet along with an estrogen blocker. Again you’ll get all the benefits of hormone replacement, but not likely as much cardiac protection, although no more risk.
In summary, it is important that you understand that you have choices in your health care. There were two decades, the 1980s and 1990s, where doctors were prescribing hormone replacement routinely for women because we knew it protected their hearts made them feel better and improve their quality of life. A major paradigm change occurred after the initial WHI results were posted, that led to an immediate 50% reduction in hormone prescriptions and is permanently biased physicians since that time. They haven’t read the updated studies that showed was actually a 40% reduction of heart attacks on women with hormone replacement, and that full hormone replacement including testosterone reduced risk of breast cancer by over 50%. These clinical studies did not make the news, newspapers, magazines, or talk shows the way the original WHI results did – which were flawed.
It is important for our community to spread the word and get doctors to read the clinical studies that have been published since 2002 WHI. We have allowed bias, and misinterpretation of clinical results, affect prescribing habits in our nation at the detriment to millions of women’s health.
In my new book, Testosterone: Strong Enough for a Man, Made for a Woman, I detail the results of those studies so that you can understand them without being an expert in reading medical literature, statistics, and clinical data. Please read this to get a better understanding of something that is of critical importance to your future health.