[PDF] Estrogeneration: How Estro
Josephine Heathershaw
The risk of things like blood clots, heart attacks, strokes, diabetes, and cancer as a result of hormone therapy are minimal, but may be elevated, especially for those with co-existing health conditions or starting hormone therapy after age 50. Generally, the size of any increase in risk for those in good health is small, and may be offset by improvements in quality of life and reductions in stress levels once they taking hormone therapy has begun. The biggest increase in risk when taking estrogen is when it is combined with cigarette smoking. In this case there is an increased risk of blood clots, and probably strokes and heart attacks. For those with an elevated risk of these conditions, or over the age of 50, forms of estrogen that are delivered through the skin, such as a patch, are generally the safest option.
In particular for those trans women over the age of 50, it might be appropriate to use testosterone blockers only, or with a lower dose of estrogen. Since most non-transgender women go through menopause with declining estrogen levels at age 50, this approach is similar to the natural female life course, and may be of particular value in those with other health risks.
Modern, healthy approaches to estrogen therapy have no risk of causing liver injury. However, in some cases, the flow of bile from the liver through the gallbladder may be slowed which can lead to an increased risk of gallstones. The degree of this increased risk is small.
Many trans women are interested in estrogen through injection. Estrogen injections tend to cause very high and fluctuating estrogen levels which can cause mood swings, weight gain, hot flashes, anxiety or migraines. Additionally, little is known about the effects of these high levels over the long term. If injections are used, it should be at a low dose and with an understanding that there may be uncomfortable side effects, and that switching off of injections to other forms may cause mood swings or hot flashes. Some trans women have encountered difficulties obtaining a consistent supply of injected estrogen due to ongoing problems with the supplier. Realistically, there is no evidence that injections lead to more rapid or a greater degree of feminization. In my practice, I generally avoid prescribing injections unless under very specific circumstances.
Contrary to what many may have heard, you can achieve the maximum effect of your transition with doses of estrogen that result in your blood levels being similar to those of a pre-menopausal, cisgender woman. Taking high doses does not necessarily make changes happen quicker. It could, however, endanger your health. You may encounter claims of complicated and at times questionable dosing regimens, or intensive monitoring of various blood tests, that make promises of drastic, almost magical effects. High doses of estrogens or other complicated hormonal regimens are not given to cisgender women who are seeking more exaggerated feminine features. In reality, beyond getting your hormone levels into the somewhat wide range of levels seen in pre-menopausal non-transgender women, there is no evidence at this time to support higher doses or complex regimens over straightforward and appropriate dosing schemes, as recommended by the Endocrine Society and our own UCSF Transgender Care Guidelines. The bottom line is that the primary predictor of feminizing effects is likely the lack of testosterone rather than levels of estrogen. Blood tests for estradiol, the most important estrogen in the body, and testosterone will be performed periodically to insure your treatment is aligned with your goals.
During the past decade there has been a substantial advance in our understanding of estrogen signaling both from a clinical as well as a preclinical perspective. Estrogen signaling is a balance between two opposing forces in the form of two distinct receptors (ER alpha and ER beta) and their splice variants. The prospect that these two pathways can be selectively stimulated or inhibited with subtype-selective drugs constitutes new and promising therapeutic opportunities in clinical areas as diverse as hormone replacement, autoimmune diseases, prostate and breast cancer, and depression. Molecular biological, biochemical, and structural studies have generated information which is invaluable for the development of more selective and effective ER ligands. We have also become aware that ERs do not function by themselves but require a number of coregulatory proteins whose cell-specific expression explains some of the distinct cellular actions of estrogen. Estrogen is an important morphogen, and many of its proliferative effects on the epithelial compartment of glands are mediated by growth factors secreted from the stromal compartment. Thus understanding the cross-talk between growth factor and estrogen signaling is essential for understanding both normal and malignant growth. In this review we focus on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling.
Breast cancer cells taken out during a biopsy or surgery will be tested to see if they have certain proteins that are estrogen or progesterone receptors. When the hormones estrogen and progesterone attach to these receptors, they stimulate the cancer to grow. Cancers are called hormone receptor-positive or hormone receptor-negative based on whether or not they have these receptors (proteins). Knowing the hormone receptor status is important in deciding treatment options. Ask your doctor about your hormone receptor status and what it means for you.
Receptors are proteins in or on cells that can attach to certain substances in the blood. Normal breast cells and some breast cancer cells have receptors that attach to the hormones estrogen and progesterone, and need these hormones for the cells to grow.
A test called an immunohistochemistry (IHC) test is used most often to find out if cancer cells have estrogen and progesterone receptors. The test results will help guide you and your cancer care team in making the best treatment decisions.
Test results will give you your hormone receptor status. It will say a tumor is hormone receptor-positive if at least 1% of the cells tested have estrogen and/or progesterone receptors. Otherwise, the test will say the tumor is hormone receptor-negative.
Hormone receptor-positive (or hormone-positive) breast cancer cells have either estrogen (ER) or progesterone (PR) receptors or both. These breast cancers can be treated with hormone therapy drugs that lower estrogen levels or block estrogen receptors. Hormone receptor-positive cancers tend to grow more slowly than those that are hormone receptor-negative. Women with hormone receptor-positive cancers tend to have a better outlook in the short-term, but these cancers can sometimes come back many years after treatment.
Estrogens are a group of hormones that play an important role in the normal sexual and reproductive development in women. They are also sex hormones. The woman's ovaries make most estrogen hormones, although the adrenal glands and fat cells also make small amounts of the hormones.
In addition to regulating the menstrual cycle, estrogen affects the reproductive tract, the urinary tract, the heart and blood vessels, bones, breasts, skin, hair, mucous membranes, pelvic muscles, and the brain. Secondary sexual characteristics, such as pubic and armpit hair, also start to grow when estrogen levels rise. Many organ systems, including the musculoskeletal and cardiovascular systems, and the brain are affected by estrogen.
To learn more about women's health, and specifically hormone replacement therapy, the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) started a large study in 1991 .It was called the Women's Health Initiative (WHI). The hormone trial had two studies: the estrogen-plus-progestin (HRT) study of women with a uterus and the estrogen-alone (ERT) study of women without a uterus. Both studies were concluded early when the research showed that hormone replacement did not help prevent heart disease and it increased risk for some medical problems.
These products are approved therapies for relief from moderate to severe hot flashes and symptoms of vaginal dryness. Although hormone therapy may help prevent osteoporosis, it should only be considered for women at high risk of osteoporosis who cannot take non-estrogen medicines. The FDA recommends hormone therapy be used at the lowest doses for the shortest duration needed to achieve treatment goals. Postmenopausal women who use or are considering using hormone therapy should discuss the possible benefits and risks to them with their healthcare provider.
Women need to be aware that taking a combined progesterone and estrogen regimen or estrogen alone is no longer recommended to prevent heart disease. A woman should discuss other alternatives of protecting the heart with her healthcare provider.
Women should discuss with their healthcare providers the value of taking combined progesterone and estrogen replacement therapy or estrogen to prevent osteoporosis. There may be alternative treatments based on a woman's health profile.
Estrogen is a steroid hormone associated with the female reproductive organs and is responsible for developing female sexual characteristics. Estrogen or estradiol is the most common form of estrogen hormone for FDA-approved treatment as hormone replacement therapy (HRT) in managing symptoms associated with menopause. Furthermore, this activity will highlight the mechanism of action, adverse event profile, off-label uses, administration and dosing, monitoring, and relevant interactions pertinent for interprofessional team members.
Objectives:
- Identify the mechanism of action of estrogen.Describe contraindications to estrogen use.Describe estrogen toxicity.Outline the working relationships among interprofessional healthcare providers to promote the safe use of estrogen and to promote medication adherence.