Bioidentical Hormone Replacement Therapy for Breast Cancer Survivors

The Protective Effect of Testosterone on the Development of Invasive Breast Cancer

Several studies support the idea that testosterone actually protects some women from developing invasive breast cancer. A study of 1267 women treated with testosterone pellets started in 2008, showed a lower incidence rate of invasive breast cancer (165/100,000 women-years) in women taking testosterone pellet therapy as compared to women who never took hormonal treatment of any type ( 271/100,000 women- years). In another study using testosterone + estrogen pellets, the incidence of invasive breast cancer was 56 per 100,000 women-years over a 9 year period of observation. These studies suggest that treatment with testosterone pellet therapy exerts a protective effect on the development of invasive breast cancer since there were considerably fewer cancer cases in the groups treated with testosterone when compared to the number of cancer cases in women who never used any form of hormone replacement therapy.

Menopausal Treatment for Breast Cancer Survivors

Both estrogen and progesterone, which are the keystones of the treatment of menopausal hormone deficiency syndrome, are not to be used by any woman who has already been diagnosed with breast cancer. The reason that estrogen and progesterone are prohibited for use by breast cancer survivors is that both hormones are capable of causing the growth of breast tissue cells, which is a process called proliferation. Proliferation, itself, is not a problem unless there has already been malignant transformation of some of the cells in the breast. Under these circumstances, estrogen and progesterone can cause cancer cells to multiply and spread.

Testosterone, the forgotten female hormone, has the opposite effect on breast tissue than estrogen and progesterone. Testosterone has an anti-proliferative effect on breast tissue and inhibits the growth of both normal and cancerous breast tissue cells. Unfortunately, many physicians are not aware of the role of testosterone therapy in treating women with breast cancer. As early as the late 1930’s, women with metastatic breast cancer were treated with testosterone injections and testosterone subcutaneous implants, which seemed to help manage the clinical course of the disease in some cases by slowing its progression, while at the same time, improving their quality of the patient’s life. Most of the early publications on testosterone treatment on breast cancer were case reports, which do not have as much scientific power as double blind crossover studies that are required today to prove efficacy of therapy. Nevertheless, such studies do give some indication of potential effectiveness and have been the starting point for many important discoveries in the field of medicine. In a small series of women with metastatic breast cancer treated with testosterone injections, there was a 9% incidence of complete tumor regression and partial regression in tumor size in 48% of patients. There was, however, a high incidence of side effects, such as acne, excess facial, body hair and voice changes, which is very common when testosterone is given by injection to women. However, when testosterone therapy is given by subcutaneous pellet implants, these side effects are much less common and can be treated with a commonly used testosterone blocker called spironolactone, which had been developed to be used as a diuretic in the 1950’s.

A major benefit of testosterone treatment is that it has positive psychological effects, which is so important for people dealing with cancer. When receiving an adequate dose, people treated with testosterone pellets experience increases in energy and motivation, which are often low in cancer patients due to justifiable increases in anxiety and depression that naturally accompanies malignant disease and its treatment. Increased motivation to fight their disease is an important mindset to be maintained by people dealing with life threatening disease.

Testosterone has an antiproliferative effect on breast tissue, stopping the growth of breast tissue cells. An example of the anti-proliferative effect of testosterone is seen with its use in the treatment of women with a benign condition known as fibrocystic breast disease. Women with this condition suffer with extremely painful, swollen, dense breasts, especially during the last two weeks of the menstrual cycle. The breasts can be so dense that mammographic x- rays cannot penetrate the breast tissue adequately to rule out cancer. This condition can be reversed with testosterone treatment because of its antiproliferative effect on breast tissue. Within 3-9 months of testosterone therapy, swelling, pain and density of the breasts are reversed and breast density is improved to the point that makes mammographic screening possible.

The effect of hormones on both normal and cancerous cells is mediated through hormone receptors. Hormone receptors, found on the surface or in the cytoplasm of most cells of the human body, are the way in which hormones regulate the many physiologic functions required to allow the human body to function. A receptor is like a lock, into which a specific hormone fits. When a hormone binds with its specific receptor, like a key entering a lock, biochemical reactions are “ turned on” that direct cells to carry out their normal biologic functions. When estrogen or progesterone molecules bind on to its specific receptors, breast tissues will proliferate because cellular division will be stimulated, resulting in increased numbers of cells. Testosterone receptors, called androgen receptors (AR) are also found in breast tissue cells, as well as in many other types of cells throughout the body. When testosterone binds onto AR receptors in breast tissue, it stops cellular growth in both benign and malignant cells. If the cells are normal, cellular expansion is self-limited. However, in cases of malignancy, should the expansion in cell numbers go on unchecked, cellular proliferation will cause the cancer to spread to other parts of the body.

When breast cancers are found to have estrogen and progesterone receptors, they are known to be estrogen receptor positive (ER+), progesterone (PR+) tumors. When estrogen or progesterone is produced naturally by the ovaries or is taken as a medication, these hormones will bind on to receptors prognosis and stimulate the growth of cancer cells. Sixty to 80% of breast cancers are ER+ and PR+ positive. The prognosis is actually best for women with cancers having estrogen/progesterone receptors because these cancer cells can be “starved to death” by depriving them of estrogen and progesterone. Several drugs, such as Letrozole, Tamoxifen, Lh Releasing Factor agonists, and aromatase inhibitors (AI), are used to drive estrogen as well as progesterone levels, to undetectable levels.

Unfortunately, both pre or postmenopausal women treated with estrogen/progesterone suppression therapy will experience intense menopausal symptoms. When treatment for ER+/PR+ breast cancer is required for pre- or perimenopausal women whose ovaries are still producing estrogen, the ovaries must first be completely turned off with Lh-RF agonists or other similar medications, effectively putting a woman into an acute menopausal state, much the same as if she had her ovaries removed surgically. Once the ovaries are shut down and there is virtually no ovarian estrogen or testosterone produced, an aromatase inhibitor therapy to block estrogen production by the adrenal glands or by fat cells in the body is started. Since the majority of breast cancer cases are found in postmenopausal women in whom the ovaries are no longer producing estrogen and testosterone, ovarian suppression is unnecessary, and aromatase inhibitors can be used on their own to suppress extraovarian production of estrogen. Although postmenopausal women have already passed the stage of menopausal symptoms, these symptoms are likely to reoccur because of a further reduction in estrogen levels beyond which the body had previously acclimatized itself.

Estrogen deprivation causes a woman treated with anti estrogen medications to be launched into an intensely symptomatic menopause. Needless to say, when deprived of estrogen, women certainly do not feel at their very best. Estrogen deficient women experience significant muscle and joint pain, as well having acceleration of bone loss, leading to the possibility of pathologic fractures. Since treatment with aromatase inhibitors is long term, lasting between 5-10 years, osteoporosis is a significant problem that must be dealt with at the same time that a woman starts on hormonal suppression therapy. Testosterone pellet therapy eliminates symptoms of extreme estrogen deficiency- hot flashes, vaginal dryness, loss of libido, brain fog, memory issues, mood swings and insomnia- and allows women to enjoy a good quality of life while undergoing treatment for breast cancer. Testosterone pellet therapy concomitant with estrogen suppression will also not only prevent the inevitable progression of osteopenia to osteoporosis, but also will cause bone regrowth. One study showed an increase of 8% per year in bone density in women on testosterone pellet therapy.

Despite the severity of symptoms caused by estrogen suppression therapy that is the mainstay of treatment for ER+ breast cancer, it seems that many physicians are still not offering testosterone treatment to their patients to relieve menopausal symptoms and to prevent the acceleration of osteoporosis. In addition, side effects caused by estrogen deprivation are unpleasant enough to seriously affect the quality of life for most women. To be sure, a person's quality of life is an important factor for a physician to consider when choosing a patient’s anti - cancer treatment protocol. With the addition of testosterone pellets, the side effects of estrogen deficiency can be attenuated to the point that a patient will be able to continue the long term estrogen suppressive therapy that is required to get the optimal therapeutic result.

Testosterone pellets should also be considered as an “add-on” to anti estrogen breast cancer therapy, both for symptomatic relief of side effects, as well as for its anti proliferative effect on breast cancer cells.Testosterone is a safe and effective medication for women with breast cancer ( See the section on the Safety of Testosterone Pellet Therapy). Testosterone pellets can be used on their own or with an aromatase inhibitor, anastrozole, added to the testosterone pellet. A testosterone/anastrozole (aromatase inhibitor) combination pellet should be used in women requiring menopausal hormone replacement therapy who may be at risk for the development of breast cancer. An aromatase inhibitor should also be used to treat women with ER+/PR+ breast cancer taking testosterone because a small amount of testosterone can be converted to estrogen by a process known as aromatization. In all breast cancer survivors, their estrogen ( estradiol +estrone) levels are periodically measured to ensure that the aromatase dose is adequate to ensure adequate estrogen suppression. Combination pellets are also a good option for people unable to tolerate oral aromatase inhibitors because of gastrointestinal or other side effects.

Summary

It is important for all women who are breast cancer survivors and who are suffering with menopausal symptoms, either as a result of natural menopause or because of treatment with anti- estrogen drugs used to treat their cancer, to be aware that treatment with testosterone is an effective, yet safe, option to make their troublesome symptoms of hormone deficiency resolve, without the use of estrogen, and to restore the quality of their lives to what it was before cancer struck. In addition, the antiproliferative effect of testosterone on breast tissue, both benign and malignant, makes it an ideal supplemental therapy to reduce the possibility of cancer recurrence or metastasis.

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