TG Medical: Cross Sex Hormones- Updated

Over the past two years I have written many articles relating to the initiation of cross-sex hormonal treatment and have usually opined that this be done in conjunction with your mental health specialist and your physician or endocrinologist, who is familiar with these hormones. It is not simply that your "Doctor Knows Best", but that your physician has the knowledge and the ability to test your hormonal blood levels to determine whether your medication is effective. From my reading, the albeit rare complications of stroke, pulmonary embolism and heart attack have been in self-medicated people who felt that more is better. In actuality, the hormonal receptors reach an early saturation point within the first 6 months and after 2-3 years your requirements for maintenance dosage should be markedly decreased. But you cannot know this without having your hormonal blood levels drawn since everybody's receptor response like breast size will be different. More hormones will not give you bigger breasts only bigger headaches. So I am going to describe the role of your physician in determining who is at risk and how you will benefit the most from the smallest effective dose of hormones.

The basics of treatment have not changed over the past 30 years, where the principles of suppressing the native hormone production and substituting the cross-sex hormones to achieve the desired secondary physical changes are paramount. But with each decade new hormones appear on the market and new principles of suppression are understood. So when you first see your Doctor he will discuss your commitment to life long hormonal changes and then proceed to examine your blood pressure, weight, all organ systems and genitals to illicit any medical history which would be a contraindication to therapy. The absolute contraindications include severe hypertension, cardiac disease, thrombophlebitis, liver problems, poorly controlled diabetes, a strong family history of breast cancer and marked obesity. Blood tests for serum testosterone, estradiol, prolactin, FSH and LH, cholesterol and serum lipids, liver, kidney and thyroid function are drawn. All of these will change to some degree as the treatment proceeds and will definitely need to be repeated every 3 months for the first two years to regulate your dosage. All of this is very expensive and that is only one reason why you should have a medical diagnosis of Gender Identity Dysphoria from your mental health specialist.

In the MTF TS, treatment consists of estrogens to achieve the female equivalent of premenopausal estradiol levels, greater than 50 picograms/dl. In most but not all, the serum testosterone will drop to less than 50 ng/dl, which approximates castrate levels and a progestational agent is added to improve breast formation. Treatment will usually begin with 50-100 micrograms daily of ethinyl estradiol or 1.25-2.5 mg of Premarin or 1-2 mg of micronized estradiol to achieve these levels. But the evolution of the transdermal patch may start a revolution. The patch can deliver a dosage range of 50-100 micrograms of estradiol per day and needs only to be changed twice per week. Transdermal Estradiol is absorbed very effectively through the skin into the bloodstream, avoids the first pass through the liver and appears to markedly decrease the risk of blood clotting. Transdermal estrogens appear to decrease Cholesterol, good, but may decrease HDLs, not good.  It has been recommended for men over 40, but it seems like it should be used by everyone. Granted Premarin is a fraction of the cost. The Combipatch combines 50 micrograms of Estradiol with .25 mg of a synthetic progestational agent, norethindrone. Typically oral Medroxyprogesterone (MPA) or Norethindrone 5-10 mgs. is given for a two week period each month or continuously to enhance breast formation. This may be stopped at any time. Monitoring by your physician at 3 months should reveal that the testes have stopped producing testosterone and that the estradiol level has been achieved. If not, the dosage will be adjusted. But what also is revealed is that Prolactin will be rising resulting in abnormal levels in 20% of the patients, and as in pregnancy, producing a breast discharge in 5%. Severe Prolactinemia can be treated with Bromocriptine.  Clinically the pituitary must be monitored for prolactin induced growth which is extremely rare. Many treatment regimens include daily Spironolactone, an antiandrogen, given in divided doses of 100-200 mg per day to decrease hair growth and improve blood pressure, while altering electrolytes which should be monitored.  Although liver enzyme elevations rarely produce clinical symptoms, women taking oral contraceptives and estrogens don�t realize that there is small incidence of liver and breast cancer along with everything else we doctors worry about.

What is new in the past decade is the class of antiandrogens such as the LHRH agonists, Leuprolide and Goserelin, which produce castrate levels of Testosterone with an injection given every 3 months. This has been the mainstay of treatment for Prostate Cancer and has been used to treat Endometriosis in women, where estrogens and progestins have been added back. It is safe with few side effects and there is a wealth of experience in treating men and women. Its effects are permanent after 1 year, but has been used in adolescents for shorter periods and found to be reversible.  There will still be a small amount of circulating testosterone which appears necessary for libido in men and women. The discovery of Finasteride and Dutasteride which block the conversion of testosterone to its active component dihydrotestosterone, reduces DHT by over 90% and seems like a more effective antiandrogen than Spironolactone. Next there is the class of androgen receptor blockers, such as Flutamide, Nilutamide and the most recent Bicalutamide. These are powerful antiandrogens and have produced breast enlargement in 50% of the men taking them without the addition of estrogens. I am definitely not suggesting these because of their serious side effects, but hope that in the future, small doses may find a place in decreasing beard growth and improving baldness, while increasing breast formation. They will not decrease testosterone to castrate levels.

At this time,  I would like to suggest a new paradigm for the treatment of the MTF TS, which would minimize the total estrogen dose and its complications. I think that I have thought about what will happen to all the known hormones and I believe that this would have minimal side effects. This should be reversible if terminated within one year.  First we would initiate an LHRH agonist, like Lupron given by injection every 4 months and within 3 weeks would reach the state of medical castration. Then at one year, we would institute the Combipatch with 50 micrograms of Estradiol and .25 milligrams of Norethindrone daily by changing the patch twice per week.  Then we could affect the peripheral hair, skin , etc. by using Dutasteride .5 mg daily which blocks, 5 alpha reductase 1 and 2, or DHT1 and DHT2, as we block the effect of the remaining testosterone without eliminating it. It may even rise a little but would be countered by the Estrogens. All of these doses could be adjusted according to their effect on serum Estradiol and Testosterone levels.  Sure there would be hot flashes and decreased bone density, but what menopausal woman hasn't faced that.

In the FTM TS, the treatment consists of injections of a Testosterone ester such as Testosterone cypionate or enanthate in doses of 200-400mg given by injection every 3 weeks. There is now a daily Transdermal patch and Androgel which can be used on the skin for maintenance therapy after the secondary sex characteristics have been achieved in 6-12 months. What needs to be monitored is the development of diabetes, increased red blood cells and liver abnormalities, which would require a decrease in dosage.  I have not talked about all the wonderful benefits of cross-sex hormone therapy, which many people speak to, only the need to have your physician help you survive and enjoy your journey.

With all the misinformation on the Internet regarding hormones, I felt that a recent review of the medical literature of 61 articles from seven major clinical centers published in the Journal of Clinical Endocrinology and Metabolism is pertinent. This included a review of the current patients and practices from The John Hopkins School of Medicine (JHSM). What was most striking was that 45% of the MTFs presenting for hormonal treatment to JHSM were on self- prescribed regimens of excessive multiple hormones. Presently JHSM is using oral Ethinyl Estradiol 100 mg/day or Conjugated Equine Estrogens like Premarin at a dose of 2.5 mg/day or Transdermal Estradiol at the equivalent of .05 mg/day for the over 40 group to suppress the serum Testosterone to less than 25 nanograms/dl.  For the FTM TS they are using injectable Testosterone Esters of 200 mg every other week or Transdermal Testosterone at 5 grams per day to achieve a serum Testosterone of about 500 ng/dl.  The Transdermal application gives more consistent blood levels. Below is a table of the other major centers with varying dosages based on clinical experience.

         Since the above treatment regimens are empiric and based on a small population it is impossible to know the true morbidity of these hormones in this population. But nevertheless the side effects have been documented  by observation and reported in each of the articles and combined in the following table with the number of observations along side. The numbers are meaningless for drawing conclusions as to what you should expect from hormones. Transdermal preparations may eventually be prescribed for all since they provide more consistent dosing and fewer side effects than the oral or injectable preparations.

         Best Wishes for your New Future.
         Cerise Richards, M.D.