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I receive frequent inquiries from transgender persons who want my advice concerning feminizing hormone regimens. Naturally, I believe that taking hormones under medical supervision is by far the best and safest course. 

But I also believe that transsexual women who decide for whatever reason to take hormones without medical supervision ought to have as much information as possible to guide them. Here are my thoughts: 

Estrogen is the most important part of any feminizing regimen. Some typical initial estrogen dosages for preoperative transsexual women who have not undergone SRS or orchiectomy (castration) are as follows:

estradiol (e.g., Estrace® or Estrofem®), 6-8 mg daily; OR

estradiol valerate (e.g., Progynova®), 6-8 mg daily; OR

conjugated equine estrogens (e.g., Premarin®), 5 mg daily;  OR

ethinyl estradiol (e.g., Estinyl®), 100 mcg (0.1 mg) daily (NOT RECOMMENDED); OR

Transdermal estrogen:

estradiol (e.g., Vivelle-Dot®, Estraderm®, Climara®, etc.), two 0.1 mg patches, applied simultaneously, changed per manufacturer’s recommended schedule (see note below); OR

Injectable (intramuscular) estrogen:

estradiol valerate (e.g., Delestrogen®), 20 mg IM every two weeks.

Occasionally half the suggested dosage may be sufficient. Sometimes the dosage will need to be increased, rarely even doubled. Beyond a certain point, larger dosages will not increase tissue response, but will only cause more side effects.

Oral estrogens are most commonly used, and are typically very satisfactory. Among the oral preparations, I prefer estradiol (or estradiol valerate, which is virtually identical). Estradiol is very inexpensive, and has low hepatic toxicity. Most clinical laboratories can perform estradiol blood levels; it is more difficult to obtain meaningful measurements of blood levels with conjugated equine estrogen or with ethinyl estradiol. Estradiol is also produced synthetically, without cruelty to animals. This is not the case with conjugated equine estrogen (Premarin®), which is prepared from the urine of pregnant mares.

Estradiol tablets can be taken sublingually (placed under the tongue to dissolve) instead of being swallowed. This may reduce possible liver toxicity, because with sublingual administration, much of the medication is absorbed directly into the blood stream, rather than being metabolized by the liver after first passing through the digestive tract. Less metabolism is also likely to result in higher levels of estradiol itself, and lower levels of its less-active metabolites, estrone and estriol. Micronized estradiol tablets are specifically designed for either oral or sublingual use and dissolve quickly under the tongue without an unpleasant taste.

Premarin® is by far the most expensive oral preparation. One of its few advantages is its relative potency, which is notably higher than estradiol on a milligram-per-milligram basis. This is because some of the equine estrogens in Premarin, especially equilin, have higher biologic potency than the estrogens normally found in humans.

Ethinyl estradiol is a chemically-modified form of natural estradiol. The ethinyl substitution results in a longer duration of action, and greatly increased potency. Consequently, typical milligram dosages of ethinyl estradiol are about one-fiftieth of typical milligram doses of estradiol. This is a preparation I do not recommend, due to its association with thromboembolic complications; see Toorians et al. (2003). Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people. Journal of Clinical Endocrinology and Metabolism, 88, 5723-5729.

I think that taking 81 mg of aspirin daily is a good precaution for persons taking oral estrogens, assuming no contraindication to aspirin exists.

Transdermal estrogen causes less clotting tendency than oral estrogen, which is possibly important to some patients. However, transdermal preparations are more expensive, and skin reactions to the adhesives employed are not uncommon. I recommend transdermal estrogen for most patients over the age of 40, to patients with risk factors such as cigarette smoking, and to patients with a personal or family history of cardiovascular disease. Transdermal patches should be changed according to the manufacturer’s recommended schedule: twice weekly for most patches, weekly for Climara®.

Injectable estrogen may cause less clotting tendency than oral estrogen and it is less expensive than transdermal estrogen. However, it requires the use of needles and syringes, and the ability to perform injections; it has a greater tendency to increase serum prolactin levels; and it is often associated with inadvertent or deliberate overdosage. Contrary to the belief of many consumers, there is no credible evidence that injectable estradiol produces superior feminization. I do not recommend the use of injectable estrogen and I no longer prescribe it in my practice.

If you have access to laboratory testing, a serum estradiol level of about 125-200 pg/ml – about one-third to one-half the normal female mid-cycle peak – is often considered ideal, at least for the first two years or so of feminizing therapy. It is not necessary or desirable to “cycle” estrogen, or any other medication, in an attempt to mimic the normal female menstrual cycle. Besides providing estrogen, a hormone regimen should also reduce testosterone to normal female levels. This usually requires adding an anti-androgen.

In persons who have not had an orchiectomy, reducing testosterone levels is also a concern. Although the desired reduction in testosterone can theoretically be accomplished with estrogen alone, the dosage required is usually in excess of what is needed for feminization. Adding an anti-androgen allows lower dosages of estrogen to be used; this is usually highly desirable. Typical dosages of anti-androgens are as follows:

spironolactone (e.g., Aldactone®), 100-300 mg daily in divided doses; OR

cyproterone acetate (e.g., Androcur®), 100-150 mg daily.

Sometimes 100 mg of spironolactone may be sufficient, but 200–300 mg is a more typical dose. The Vancouver group uses up to 600 mg daily, apparently without problems. Spironolactone is fairly inexpensive, is readily available, and is usually quite well tolerated. In my opinion, it should be regarded as the anti-androgen of choice for most patients. Cyproterone is actually a progestin (see below), but it is used primarily for its anti-androgenic effects and only secondarily for its progestational effects. It is not available in the US, but is popular elsewhere. One disadvantage of cyproterone is that it counteracts some of the desirable effects of estrogen on blood lipids. Cyproterone, when used in combination with estrogen, may also share some of the increased risks associated with the synthetic progestin medroxyprogesterone when so used (see below).

If you have access to laboratory testing, a serum testosterone level within the normal female range – about 5-85 ng/dl for total testosterone, or 0.1–2.2 pg/ml for free testosterone – is usually considered ideal. Within the female normal range, lower numbers are not necessarily better. Progestins (progesterone and synthetics) are sometimes added to a hormone regimen. I consider them unnecessary for most patients.

Progestins are most often given in an attempt to increase breast development. Based on limited anecdotal evidence, I think that improved breast development sometimes can occur, but that the effects are usually not very significant. Progestins can also inhibit testosterone production, and are sometimes used for this purpose. I consider progesterone and other progestins to be unnecessary for most patients, and I prescribe them only rarely. If you decide to take them, here are some typical dosages:

medroxyprogesterone (e.g., Provera®), 5-10 mg daily; OR

micronized progesterone (e.g., Prometrium®), 100 mg twice daily; OR

Injectable (intramuscular) progestins:

medroxyprogesterone (e.g., Depo-Provera®), 50 mg every two weeks; OR

progesterone in oil, 50 mg every two weeks.

Oral medroxyprogesterone, the most commonly used product, is very inexpensive, but it has the disadvantage of counteracting some of the beneficial effects of estrogen on blood lipids. Some people find that it causes depression or mental irritability. The recently published Women’s Health Initiative study has also documented an increased incidence of adverse complications in women taking medroxyprogesterone in combination with conjugated estrogens for hormone replacement; this increased incidence of adverse complications was not found with conjugated estrogens alone. Micronized progesterone is a reasonable alternative in those who want to take a progestin. It does not counteract the beneficial effects of estrogen on blood lipids. But micronized progesterone is more expensive, and is often harder to obtain. When taken by mouth, it is partially metabolized to 5-alpha and 5-beta pregnenolone; these metabolites can act as natural tranquilizers, and may promote sleep. This effect may be desirable in patients who suffer from anxiety or insomnia. After orchiectomy (castration) or SRS, dosages can be reduced. Following SRS, anti-androgens can be discontinued, and estrogen dosage can usually be decreased to one-half or one-quarter of the pre-op dosage, i.e.:

estradiol (e.g., Estrace® or Estrofem®), 1-2 mg daily; OR

estradiol valerate (e.g., Progynova®), 1-2 mg daily; OR

conjugated equine estrogens (e.g., Premarin®), 0.625-1.25 mg daily; OR

ethinyl estradiol (e.g., Estinyl®), 20-50 mcg (0.02-0.05 mg) daily; OR

Transdermal estrogen:

estradiol (e.g., Climara®, Estraderm®, or equivalent), 0.05-0.1 mg, changed per manufacturer’s recommended schedule; OR

Injectable (intramuscular) estrogen:

estradiol valerate (e.g., Delestrogen®), 5-10 mg IM every two weeks.