Testosterone for Women – The Most Important Webinar and Testosterone Study to Date

Testosterone for Women – The Most Important Webinar and Testosterone Study to Date

Testosterone for Women- The Most Important Webinar and Testosterone Study to Date

April 2023

April’s webinar will be the last in the series of webinars addressing the use of testosterone in women. This last webinar is most pertinent to women that have active breast cancer, are breast cancer survivors, or those that wish to protect against breast cancer. The intent of these testosterone webinars is to introduce medical studies/literature/discussions/expert opinions as to the safety and efficacy of testosterone use in women. We addressed the how, where, when, and why issues surrounding the use of testosterone in the prior webinars. We have attempted to provide you with as much literature as we could find that no other medical academy or association has provided. One of my pet peeves is the continual denigration for the use of testosterone by so-called experts that claim the use of testosterone is not supported by the literature or science. Nonsense. Seemingly I find that the authors of the various testosterone guidelines are the specialists that have the least experience in prescribing testosterone as well as the least exposure to the plethora of literature supporting the safety and efficacy of testosterone, in both women as well as in men. The credible literature that exists, the long-term safety data proving no harm, as well as the tremendous experience of experts fully support the use of testosterone in women. Not using testosterone replacement puts women at risk of many disease states as well as an increased risk of morbidity and mortality. The dictum in medicine holds true for not causing harm with any therapy. On the other hand, based on the tremendous literature and science proving benefit, it would appear obvious that we are causing harm by not prescribing testosterone to women.

Treat the Patient not the Level

As unfortunate as it is, the specialists that we would expect to know the most about hormones are endocrinologists, gynecologists, and oncologists. However, the specialty guidelines dictate that we must stay within the box and not deviate outside that box as it pertains to lab test results. In other words, serum levels are used to guide therapy and levels must not be allowed to extend above the range of normal based on that particular lab test. Conceptually, we are worlds apart from medical society guidelines as we choose to treat based on symptoms and symptom improvement and not numbers. We use serum levels as a guide to therapy but not as the only marker to adjust therapy. Some authors will use a supraphysiologic level to restrict therapy thereby ignoring the patient’s symptoms. All the testosterone studies demonstrate that hormone levels do not predict symptoms or improvement in symptoms. Symptoms, therefore, should guide therapy and not numbers.

Women, Testosterone and Breast Cancer

This entire webinar series for women is predicated on the studies and literature demonstrating that symptom improvement, and breast cancer treatment and prevention, can only be achieved with supraphysiologic levels and doses of hormones. Studies demonstrate that maintaining serum levels with the physiologic range of “normal” provide no benefit, yet that is what the expert guidelines dictate. AACE and ACOG published guidelines are based on opinion and not science. Our recommendations are based on outcome studies demonstrating what doses and levels work and what doses and levels don’t work. This has created significant confusion and problems for clinicians that measure levels as our peers frown upon hormone levels that are outside or above the range of “normal.” This webinar will continue to address those issues. In the current study reviewed in this webinar, testosterone use in high doses for prolonged periods of time is safe in women. In this study the researchers studied women trans-gendering to males, and they proved that high dose testosterone when used for 6 years was safe without worry or concern of supraphysiologic levels of estradiol from aromatization.

Guidelines vs What the Research Shows

Upon reading guidelines from the various medical academies, the recommendations from the foregoing academies for use of testosterone in women are recommended only for the treatment of hypoactive sexual desire disorder. The plethora of data demonstrating the benefit of testosterone in protecting against cardiovascular disease, cerebrovascular disease, breast cancer, diabetes, osteoporosis, and dementia is ignored. Despite the supporting data, expert opinion often ignores the literature that supports multiple health benefits as well as quality of life benefits. Their claim is always that there is no long-term study or safety data. I presented multiple studies demonstrating long-term safety and benefits that seem to get ignored by some authors in order to conform to the bias against the use of compounded bioidentical hormones by some medical societies. Since testosterone is not FDA approved for women and compounded testosterone fills that niche, and since ACCE and ACOG are against the use of compounded hormones, then we would expect to encounter this pushback and denigration against the use of compounded testosterone. Experts claim that there are no long-term studies, but this is not true as I presented many of those studies in this webinar series. There are no long-term studies on most of the commonly prescribed medicines that we use on a daily basis, but that seems to be OK. It appears that hormones, particularly testosterone, are held to a different standard. The many peer-reviewed studies published in our most peer-reviewed medical journals get conveniently ignored thereby putting the health of women at risk when the guidelines reflect only a restricted use for testosterone in women. Nevertheless, there are many health benefits for women to enjoy besides the improvement in sexual function. I have reviewed the many health and feel-good benefits in the prior webinars. It is unconscionable that we ignore this data.

Testosterone and Breast Cancer

The only harm demonstrated in long-term studies is not any serious harm, rather it involves side effects on the skin and integument (acne & hirsutism) that are easily remedied by dosage adjustments and use of spironolactone. Still, what are any potential major side effects, problems, complications, and harms other than skin side effects? We are still searching for some harm, but our peers are quick to point out a potential harm in the form of estrogen-related side effects from the aromatization of testosterone into estradiol and the resultant stimulation of the endometrium resulting in endometrial cancer.

Since estradiol is derived from testosterone, it only makes sense that prescribing testosterone to women without adequate progesterone opposition would likely result in endometrial cancer. Most oncologists will assume that any testosterone that is administered to a woman who is a breast cancer survivor will be contraindicated due to the assumption that any dose of testosterone will increase the E2 levels thereby making the use of testosterone contraindicated. As the result, most oncologists will reject the use of testosterone in breast cancer patients citing these concerns of increased breast cancer and endometrial cancer. However, testosterone has been a very successful chemo-hormonal agent in the treatment of breast cancer for over 40 years, without any demonstration any worsening of breast cancer or endometrial proliferation. So, who is right and how should we proceed?

Progesterone and Testosterone has  Apoptotic Effects on Breast Cancer Cells

In the last 5 testosterone webinars I presented all the data and studies demonstrating the tremendous benefits of testosterone in treating and preventing breast cancer. Assuming that prescribed testosterone will raise the levels of E2 in women from aromatization, then perhaps the apoptotic effect of testosterone overrides any risk of increased E2 levels from aromatization. However, and more importantly, there is not one study demonstrating any increase in endometrial proliferation or endometrial cancer in women that have been prescribed testosterone-alone. If there truly was an increase in E2 levels in women taking testosterone, then we should observe it in some study, but we don’t. There is ample evidence of tamoxifen causing an increase risk and incidence of endometrial cancer due to the stimulatory effect of tamoxifen on the endometrium. Unfortunately, most oncologists will reject any suggestion to simultaneously prescribe micronized progesterone for endometrial protection when tamoxifen is prescribed. Again, their thought process is that “progesterone” causes breast cancer and therefore is contraindicated in breast cancer patients. Unfortunately, oncologists are not hormone experts and will not understand that both micronized progesterone and testosterone have apoptotic effects on breast cancer cells, and both have been successfully utilized in the treatment of active breast cancer. I have successfully treated many breast cancer patients with both P4 and testosterone, always providing the patient with the literature and RCTs demonstrating the benefits of these hormones in treating active breast cancer. I have also treated and reversed endometrial proliferation from tamoxifen use, when the oncologist insisted on a prophylactic hysterectomy and rejected any use of P4 for endometrial protection. Unfortunately, there is no venue for oncologists to learn/understand/appreciate the difference in various hormones.

So, where do we go from here? Well, to the medical literature, of course. Throughout this entire webinar series, I have presented studies proving that symptom improvement typically only occurs with high dose testosterone replacement and at supraphysiologic levels. As you can imagine, many PMDs and peers have difficulty when seeing lab reports for their patients that demonstrate supraphysiologic levels (which is why I insist that the PMD never check hormone levels). This is most disconcerting in breast cancer patients where it is assumed that testosterone use increases levels of estradiol thereby worsening breast cancer risk. And I know that this will not make sense to you, but it doesn’t. All testosterone studies demonstrate an apoptotic effect on breast cancer cells via stimulation of the AR.  For years now, I have stated that testosterone administration does not increase the serum level of E2 in women and I base that on measuring serum E2 levels in every patient to whom I prescribe testosterone. It only makes sense that using testosterone should increase estradiol levels via aromatization, particularly in the high doses recommended to breast cancer patients. Certainly, increasing E2 levels which would increase breast cancer cell stimulation is the opposite of what we would want to do. However, in every patient to whom I prescribe testosterone, I measure testosterone and E2 levels. And the E2 levels DO NOT INCREASE. It did not make sense to me either, but that is what I continuously observed. In fact, most have E2 levels that are in the low level of menopause, around 10-20 pg/mL. I will show you those lab results along with case presentations in this webinar with the explanation as to why this unexpected result occurs. I know, you still don’t believe me because it just does not make sense. Well, I didn’t believe it myself as it made no sense to me either.

Testosterone Does not Increase Estradiol Levels in Women

This webinar will provide the literature proof that testosterone administration to women does not increase E2 levels (it does in men but not in women). Researchers studied high-dose testosterone replacement in biologically female patients that were transgender males (females became males). The expected result was that testosterone administration should increase E2 levels. It didn’t. Not only did the E2 levels not increase, but they decreased! The concerns regarding aromatization of testosterone into supraphysiologic levels of E2 were not evident. Even AACE guidelines state that E2 levels in transgender males should be lowered with aromatase inhibitors to prevent endometrial malignancies. The alternative is prophylactic hysterectomy and oophorectomy. However, many studies prove the decrease in E2 levels by several different mechanisms which we will review. A regression analysis revealed a statistically significant decrease in BMI and E2 levels with increasing serum testosterone levels.

OBJECTIVES:

  1. Review studies demonstrating serum E2 levels achieved with high dose testosterone replacement in transgender males (originally biologically female XX) is not of concern.
  2. Discuss the lack of data demonstrating any MACE or adverse health outcome to high dose testosterone administration to transgender males, particularly in female reproductive tissues.
  3. Recall that outcome studies proved a decrease in E2 levels in women after testosterone administration, the opposite of what would be expected.
  4. Contrast the different effects in outcome studies between men and women regarding aromatization of testosterone into E2.
  5. Evaluate other outcome RCTs demonstrating no evidence of an increase in serum E2 levels that could act as an added cancer risk to female reproductive tissue.
  6. Identify those studies that prove there is no evidence for elevated estradiol levels that would need to be mitigated with aromatase inhibitors as dictated in recent AACE guidelines.
  7. Review labs demonstrating typical E2 and testosterone lab values attained in my patient population of breast cancer patients.
  8. Discuss the risks and harms of estrogen deprivation from the use of testosterone-alone.

CASE PRESENTATION:

Your 58 y/o female patient, s/p mastectomy for breast cancer 6 years ago, calls to explain that she does not feel well after stopping her hormone regimen as advised by her new oncologist. The admonition and belittling by her oncologist for taking hormones was very unsettling and disconcerting as she was led to believe that the hormones that she had been taking were harmful and could lead to increased risk of cancer recurrence. Now she feels miserable off the hormones, the same as before when she stopped her hormone regimen which consists of high dose P4 and testosterone. Your patient wants to continue her HRT regimen but not if it could cause potential harm. She also does not wish to go against the advice of her very prominent and experienced oncologist. A lengthy discussion ensued as you had to explain the differing viewpoints and that the response from the oncologist is expected and appropriate based on their understanding of hormones and cancer. All hormones are forbidden in breast cancer survivors based on the understanding that both estrogen and progestin increase the stimulation of breast cancer.

After completing the webinar series on testosterone for women, you provide the various studies demonstrating the safety and efficacy of testosterone, both as a treatment for active cancer as well as prophylaxis against breast cancer recurrence. The same goes for micronized progesterone. In addition, both P4 and testosterone can mitigate the side effects of tamoxifen and aromatase inhibitors, which the patient stopped after 5 years. Without being condescending toward the oncologist, you politely explain that the oncologist may not be aware of the literature support for testosterone and P4 in being so efficacious in both the treatment of and prevention of breast cancer. The oncologist is just doing what they were taught and trained to do. At the risk of being confrontational and having a poor working relationship with the oncologist, you advise the patient not to give the extensive literature review to the oncologist. Rather instead, you advise the patient to inform the oncologist that she will stop the HRT regimen and to show appreciation for the advice and education on hormones. The patient can then base her treatment decision on all the literature that you have provided demonstrating the tremendous benefits and lack of harm in the HRT regimen you have prescribed.

Respectfully, Neal