Transgender Care Health Information Archive
A Look at Medications
Forms of Feminizing Hormone Therapy
The general process of supplementing a woman's natural hormones is often called hormone replacement therapy or HRT. The oldest form of supplemental hormones is estrogen. When estrogen is taken alone (that is, not mixed with a progestin), it is called unopposed estrogen (also, estrogen replacement therapy or ERT). When estrogen is taken in combination with progestins, the process is called combined hormone therapy.
For transgender women, the standard HRT regimen is inadequate. The latest and most effective therapies include more potent estrogens and anti-androgens. This combination of medications not only offers greater feminization, but also provides a greater reduction of the masculinizing effects from past virilization. Each regimen and form of administration not only has its own specific benefits, but also carries with it a variety of differing risks.
Over the years, we have used many different feminizing and de-masculinizing drugs with our patients in order to maximize the positive benefits while reducing any negative side effects. The feedback from these ongoing treatment methods coupled with consultations with other professionals, and discussions with patients who have experienced other regimens have allowed us to compile a sizeable amount of data concerning the administration of hormonal therapies.
The following is a brief synopsis of medications that are used in feminizing hormone programs.
ESTROGENS - ORAL USE
17-Beta Estradiol provides the most potent estrogen available, and is most commonly taken by mouth. It may also be administered by way of a skin patch or injected into muscle, whereby the drug travels expeditiously through the bloodstream to the areas it affects or targets.
Oral estradiol provides a very effective means of feminization. Its dosing and subsequent adjustments, like other medications to follow, is dependant on measured testosterone levels, the degree of feminization achieved, side effects and other impediments to a healthy condition.
Oral estradiol is usually supplied in 0.5 mg (milligram), 1.0 mg, and 2.0 mg tablets.
Conjugated Estrogens-Naturally Occurring (e.g., Premarin)
The most common mixture of natural estrogens is called Premarin. Derived from the urine of pregnant mares, Premarin contains a number of different (conjugated) estrogens and is obtained through the extraction process. Compounds derived from such a process not only subject animals to unduly harsh conditions, but may contain additional substances that create a potential for unknown or adverse effects. In our observation, there is a greater likelihood of mood swings and depression seen in patients using naturally derived estrogens as compared to synthesized preparations such as estradiol.
Conjugated Estrogens-Synthesized (Cenestin)
Conjugated estrogens may be synthesized also. One such medication, Cenestin, is a slow-release conjugated estrogens product derived from plant sources. Cenestin contains the same three primary and six minor estrogens found in Premarin.
Other plant-derived estrogens, called esterified estrogens, are usually made from modified soy (Estratab, Menest).
Estropipate (Ogen, Ortho-Est) is a version of estrone, a weaker form of estrogen.
ESTROGENS - FOR INJECTION
Estradiol Valerate is formulated as a longer-acting product that is usually contained in an oil preparation. Like oral medications, injectable preparations are manufactured in differing strengths. In the case of Estradiol Valerate, the drug is typically formulated in a concentration between 10mg to 40mg of active ingredient per milliliter (mL).
While some may be fearful of injection, the amount administered will usually be contained in one mL. To give an idea about that amount of liquid, a small spoon holds about 5 milliliters. Estradiol Valerate may be typically injected weekly to monthly, with the frequency/concentration based on the measured testosterone levels for the patient.
The more direct route of administration provided by injection may speed the physical change by creating a higher and more constant source of estrogen. Ideally, injection should require less processing by the liver, but all to often improper administration (poor or no monitoring, self-medicating, etc.) instead creates undue health risks.
ESTROGENS - TOPICAL USE (Through the skin)
Interestingly, some of the most ineffective as well as some of the most beneficial preparations are available in topical form.
Estrogen creams (e.g., Premarin cream) are sometimes applied to areas of the skin, such as the breasts. The benefits from such an approach usually range from very minimal to unfelt.
Medication skin patches, also called transdermal or percutaneous patches, provide a very effective means of medicating. In this approach, the estrogen (estradiol is used) is transferred into the body directly through the skin. The transdermal approach offers ample delivery of medication for full feminization. And its consistent and prolonged release make for a safe and sensible approach.
But the transdermal approach is pricey, being probably the most expensive means of administration. Some individuals suffer skin irritation related to the adhesive. For others, the presence of a patch is awkward or tends to come loose from the skin, especially during sustained activity, such as sports or outdoor activities. The adherence problem can be addressed with the use of a skin preparation that helps the patch stay in place even in the presence of moist conditions or heavy perspiration. See A Sticky Solution to Transdermal Adhesion Problems.
Transdermal patches uniformly contain estradiol as the active medication, produced in 0.05mg (50 micrograms, 50 mcg) and 0.1 mg (100 mcg) concentrations, and are branded under a variety of names such as Climara and Alora. The reader will notice that the dose amount contained in the patch is about one-tenth to one-twentieth as the same drug that is taken orally. These concentrations are considered potent since transdermal entry of the drug is many factors more efficient than oral administration.
PROGESTINS (PROGESTERONE) - ORAL USE
As mentioned in Section 5, progestins have an arguable positive effect for the transgender individual. It is likely that if a progestin is chosen, a minimal dose of oral medroxyprogesterone acetate (Provera) may be given on a cyclic basis. Such a typical regimen may provide for its use for about ten days of the month. Less likely would be its use on an uninterrupted basis.
PROGESTINS (PROGESTERONE) - FOR INJECTION
A progestin may also be given by injection. The same medication, medroxyprogesterone acetate, is available in an aqueous suspension for injection. It is typically branded as Depo-Provera and its typical use is to provide long-term (about three months) contraception from a single injection. Another injectable medication sometimes chosen for transgender use is hydroprogesterone caproate (Proluton Depot). From our experience, we do not see a benefit from the use of injectable progestins. Patients have regularly expressed complaints and have suffered adverse side effects.
The use of an anti-androgen has been used for many years by endocrinologists as a biochemical means of controlling unwanted hair growth in the genetic female. In recent years, this treatment approach had been introduced in treatment of transgendered women and is now being widely practiced.
It has been our experience that anti-androgens have a role second only to estrogen in the feminizing process. Further, without the use of anti-androgens, adequate and desirable demasculinization will likely be greatly curtailed. And following genital surgery or castration, continued use of anti-androgens is strongly recommended if continued feminization is expected.
The drug most commonly used for the task of diminishing one's response to androgens is spironolactone (branded as Aldactone). Like many other drugs in the category of anti-androgen, spironolactone is used other than for its primary or generally intended purpose. In the case of spironolactone, it is a diuretic and anti-hypertensive medication.
Spironolactone is a good choice for an anti-androgen. It is generally well tolerated, even when administered over a period of years. And when by happenstance, a mildly hypertensive patient enters into transgender treatment, often spironolactone can be provided as a substitute; by doing so, the medication now serves a dual purpose. While spironolactone is a potassium saving diuretic, the normal monitoring of blood chemistry during transgender treatment assures its safe administration.
Patients often report increased unpleasant side effects (such as a need for frequent urination) when doses over 300mg per day are taken. Typically doses of 200mg daily or less are well tolerated.
Finasteride (Proscar, Propecia)
Another good choice for an anti-androgen is finasteride (Proscar, Propecia), and is able to be used in concert with spironolactone. The primary use of Proscar (finasteride 5 mg) was in the treatment of benign prostatic enlargement, but with its reintroduction as Propecia (finasteride 1 mg), the drug is being largely marketed to promote scalp hair growth. For transgendered women, finasteride when given in the larger dose promotes not only scalp hair growth but acts as an potent anti-androgen as it is highly effective in inhibiting the conversion of testosterone to DHT (dehydrotestosterone) responsible for male sexual characteristics. Finasteride is usually physically well tolerated over long durations, but is expensive.
Anti-Androgens whose potential risk may outweigh their benefit
Keep in mind that unlike estrogens, the drugs that are used as anti-androgens, when initially released, were typically intended for a variety of medical conditions, including some very serious conditions. In effect, through clinical use, these drugs have been re-purposed for a feminization regimen.
Typically, drugs that address more serious medical conditions (e.g., cancer) have effects that may be not only potent, but harmful and unexpected, as their potential hazards may far outweigh their benefits. Simply put, these drugs may be more harm than good. Such drugs include:
Leuprolide acetate (Lupron)
Leuprolide acetate (Lupron) is used as an anti-androgen as it has the potential to reduce testosterone to castrate levels. It is an analog of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. Lupron is normally used in the treatment of advanced prostatic cancer when orchiectomy (removal of the testicles) or estrogen administration are either not indicated or unacceptable to the patient.
Lupron does carry a variety of risks that have been associated with its use including a variety of cardiovascular difficulties (congestive heart failure, ECG changes/ischemia, blood pressure changes, murmur), musculoskeletal pain and fluid retention. While the non-transgender male suffering from prostatic cancer may consider these risks acceptable as compared to castration or estrogens, these same risks seem absurd in the parlance of a feminization regimen.
Flutamide (Eulexin) is another drug used ordinarily in the treatment of prostatic cancer and has somehow been adopted as acceptable medication in transgender treatment. Flutamide carries the risk of liver injury to the patient.
Ketoconazole (Nizoral) similarly carries the potential of injury to the liver, however its normal use is as an anti-fungal agent.
Cyproterone acetate (Androcur)
Cyproterone acetate (Androcur) is an anti-androgen that has been used to treat hypersexuality and sexual deviation in men; it is also used in the treatment of cancer of the prostate. It is used, in part, to treat severe acne in women. Its high-dose treatment sufficient for a feminization regimen may cause liver damage, resulting in jaundice or hepatitis.
When one considers the advancements and availability of sound medical management in the area of transgender treatment, most often the feminization regimen required for the transgendered individual can be handled with little complication. Today, there are well trained providers available worldwide.
Sadly, too few individuals have addressed their own internal conflicts and fears concerning their transgenderism. As a result, addressing one's transgender concerns may unsettle the individual wishing to pursue proper and sound medical treatment. The individual who may readily appreciate the risks associated with self-medication and less than acceptable therapies under other circumstances, may opt for such solutions in the transgender milieu. And accordingly, the likelihood of serious health risks and poor outcomes is unacceptably high as a result. Sensibility and proper medical management are the cornerstones for a successful outcome.
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