Transgender Therapy: Male to Female Transition

A study in the Netherlands suggested that 1 out of every 12,000 men are transgendered. The exact prevalence in the United States however is unknown. Most male to female (MTF) transgender patients relate a long-standing history of feeling uncomfortable in their assigned gender. Many MTF patients note a strong identification with the opposite sex, typically known as gender identity disorder or gender dysphoria, since childhood.

The cause of transgenderism is unknown, although an autopsy study reported changes in the hypothalamus of MTF transgendered patients which were identical to genetic females (JCEM 2000; 85:2034-2041).

Once psychiatric issues have been eliminated as a cause for altered gender identity, hormonal therapy is traditionally prescribed to aid in the transition of MTF patients. Unfortunately, there are few long-term studies to guide physicians regarding the optimal dosing and duration of medical therapy. Compared to other hormonal disorders, the treatment of transgendered patients is thus far more dependent on a physician's experience, as compared to published, data-supported clinical guidelines.

For most MTF transgendered patients, treatment goals include breast development and the reduction of male pattern hair growth.

Voice change requires re-training at a qualified center. It is not responsive to hormones.

Estrogen therapy is the primary hormonal therapy used to induce breast formation. Although many forms of estrogen are available, most endocrinologists begin treatment with an oral estrogen. Oral estrogens are typically selected since this form of therapy has been used in the majority of clinical trials.

Many MTF transgendered patients are interested in intramuscular (IM) estrogen due to suggestions within the transgendered community of improved breast tissue response. Due to the virtual absence of IM treatment regimens in most clinical trials, and the subsequent lack of safety data, IM regimens are not recommended.

Traditionally, estrogen therapy is begun at a low dose, with a cautious dose escalation over 3-12 months. Breast development is typically noted at 6-12 months. There is significant variability among MTF patients regarding time for breast response, and the degree of response. Breast development may be more evident in people who are thin. Anecdotally, transgender patients who are 10 years or less post-pubertal have a more significant breast response to treatment. There is however significant variability.

Blood testosterone levels should be monitored once estrogens are begun with a goal testosterone of <50 ng/dl. The greatest risk associated with estrogen therapy is a 20x increased risk of clots in the blood vessels. Fortunately, there doesn't appear to be an increased risk of heart-related death. Clotting complications typically appear within the first 4-12 weeks of therapy, but may occur at any time. Aspirin therapy is often added to estrogen treatment regimens because of this risk. If a clot occurs, estrogen therapy is discontinued to allow evaluation and treatment. Therapeutic options after a clot must be reviewed with a hematologist (blood specialist). This may include other medical therapies or a cautious re-trial of low-dose estrogen with appropriate anti-clotting protection. Whatever the treatment, careful regular follow-up is critically important.

A hematology evaluation may be recommended by your physician to rule out an underlying clotting abnormality which was "exposed" by estrogen.

Other potential risks of estrogen therapy include an increased rate of gallbladder stones, abnormal liver and lipid blood tests, mood changes, high blood pressure, breast cancer and elevated prolactin levels. Estrogen related risks appear to be dose-related. They may be more significant in older MTF patients. It is critical that you review all risks with your physician before beginning treatment with estrogen.

Your pre-treatment evaluation should include a thorough medical history and physical exam. An EKG should be included if there are heart-related risks. Laboratory testing should include a baseline comprehensive metabolic profile, as well as blood testosterone, estradiol, lipid, and prolactin levels. Blood tests should continue to be monitored throughout treatment. Discontinuation of cigarette smoking is an absolute necessity before estrogen therapy should be considered.

If a patient proceeds with sex reassignment surgery (SRS), the estrogen dose will be reduced significantly.

Although some studies suggest a menopausal replacement dose in SRS patients, this dose has not been sufficient for most post-op MTF patients in my practice.

"Top surgery" may also result in lower estrogen requirements.

Other potential changes associated with estrogen therapy include a reduction in libido (sex-drive) and testicle size as well as erectile dysfunction. There is a considerable variation in sexual response to hormonal therapy, with some patients reporting little or no effect.

Progesterone therapy has been recommended by some authors as an adjunct to estrogen. Since there is no convincing evidence to support this, as well as potential risks associated with Progesterone, I don't recommend this in MTF patients.

Anti-androgens such as Spironolactone are often added to aid in breast development and reduce male pattern hair growth. These drugs are typically well tolerated.

Combination Estrogen-Spironolactone therapy typically results in a reduction of male pattern hair growth within 6-12 months. Most MTF transgendered patients note a significant reduction in body hair, as well as a marked reduction in the need for electrolysis and other hair removal treatments, after one year of treatment. The response of facial hair to hormonal therapy is less significant.

If tolerated, and carefully managed, hormonal therapy can have a significant positive impact on the life of transgendered patients.