Male to Female Hormone Therapy- Action & Cautions.

NOTE- There is so much information on the web for hormone use. The following is based on my clinical experience with clients and current research; it is not offered for self treatment or but to assist educational knowledge.

ESTROGEN-To combat the effect of Testosterone we need to use two types of medication. Estrogen will create the female characteristics and secondly suppress testosterone; it can be given by pill, injection or transdermal; by patch or gel.

I prefer to offer the trans-dermal method, as it appears to be safer and easier on the body compared with oral administration (Toorians , Thomassen, Zweegman, Magdeleyns, Tans, Gooren, Rosing. 2003).  For instance, Estrogen increases the chance of blood clotting and therefore heart attack or stroke; also it increases triglyceride levels, which can also result in heart disease.

ANTI-ANDROGEN- The second medication is an anti-androgen, which block Testosterone and allow estrogen to work on the body;

Spironolactone -This drug was originally developed as an antihypertensive/diuretic; it is also a weak androgen receptor antagonist. It is much less effective as an antiandrogen than cyproterone or flutamide, but can find use in patients who have hypertension or severe fluid retention, either pre-existing or as a result of hormone treatment. Side effects may include lassitude, loss of concentration, and various gastrointestinal problems. There is a risk of potassium retention. Doses range typically from 100 to 400mg daily.

Cyproterone Acetate - (brand names Androcur, Cyprostat). It is an androgen receptor antagonist and weak gonadal androgen production inhibitor; normal dose is 50mg daily, which may be increased to 100 or in exceptional cases 150mg daily if required. In these doses there are some risks associated with the drug, particularly a heightened risk of thromboembolic disease or liver damage. Carbohydrate metabolism changes are also reported; patients should receive regular blood tests (LFT and fasting glucose) and BP checks. Possible side effects include severe lassitude, loss of concentration and depression, also weight gain and nausea. Anecdotal reports suggest that the side effects can be lessened by taking the drug after meals; opinions differ as to the best time of day to take a single dose to minimize the tiredness effect: patients are best advised to experiment for themselves, though after lunch or after the evening meal seem to be the usual choices.

Flutamide -This is a relatively new drug which has been used with success in some transsexual patients, particularly those who have experienced unacceptable side effects with cyproterone. There is relatively little clinical data available for this drug in transsexual patients. It is a strong androgen receptor antagonist. Like cyproterone it can be hepatotoxic, it can also have significant adverse haematological effects (reduced platelet, leukocyte or erythrocyte count) or cause hypertension, and it can also produce less serious side effects such as fluid retention. Regular LFTs and blood checks are advisable when using this drug. This drug also produces psychological side effects which can be severe in some patients. Depression, anxiety or nervousness can be extreme, and patients should be made aware of this possibility. Lassitude, insomnia and gastrointestinal disturbances have also been reported. Typical dose is 250mg to 750mg daily (one to three 250mg tablets).

Finasteride -This drug is not suitable as a general antiandrogen, but can be useful in countering male-pattern baldness in transsexuals. Classed as an androgen conversion inhibitor, it blocks the conversion of testosterone to DHT. It is generally free from significant side effects, but does not appear to affect male sex drive. Typical dosage is 5mg daily.

PROGESTERONE- To use or not to use? There has always been debate over the use of Progesterone in a cross-hormonal therapy there is some indication that progesterone administered with estrogen may promote extra breast growth by increasing the volume of the lactation and ducting tissues. Some studies relating to birth control pills usage by natal females would seem to show that progesterone’s administered with estrogens reduce the risk of cancer from administration of estrogens alone. Yet, in some people, synthetic progesterone’s have a slightly androgenic effect and can apparently even antagonize estrogen absorption resulting in testosterone increase, although many believe that the use of non-synthetic progesterone may overcome this adverse effect and provide a healthier balance for an aggressive estrogen dosage.

Post-opProgestrogens are not necessary for physical health post-op, but many post-ops find them beneficial psychologically, and if the patient is still feminising then the usual benefits of progestrogen therapy (particularly in breast size and texture) will be obtained.

Does that answer the question of progesterone use? I think the jury is still out and that it’s use is debatable as the benefit of increased breast form may be outweighed by the possibility of increased mood swings and increased androgen/ testosterone.

It is important to remember that the M2F is and remains genetically male and we must guard against treating as a genetic female, for instance; I see no value in cycling to mimic female menstrual cycle as this results in hormonal shifts and physiological and psychological changes in both genders.

Cycling, (not with a bicycle)- Some endocrinologists attempt to mimic a female menstrual cycle by decreasing or eliminating estrogen for one week of the month and/or adding or increasing progesterone for the same week. Generally this type of treatment is only preformed with patients who are also receiving anti-androgens so as to mitigate the effect of causing large variations in the endogenous androgen level. At this time we are not aware of any specific evidence that this type of treatment is either beneficial or harmful, although there are some indications that cycling progesterone’s may decrease the beneficial effect of estrogen on cardiovascular health, and may also promote extreme mood swings similar to PMS in genetic females.

Anticoagulants- It is common practice to administer low dose Aspirin (ASA) especially to patients over 40 yrs. to reduce the risk of clotting and DVT formation. This has been questioned in the past as to the increased risk of gastrointestinal inflammation and ulcer formation, however, a dose of 80mg. daily may be prudent as the benefits of reduced clot formation for cardiac, pulmonary thrombi and stroke and especially in patients with cardiovascular disease and/ or hypertension (High blood pressure).

-If there is a concern about the use of anti-coagulants the use of transdermal estrogen has shown to have benefits in anticoagulation opposed to other routes of administration.

     “Oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic     potential, whereas opposed transdermal estrogen appears without any substantial effects on hemostasis. Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen, they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women, especially to those at high risk of thrombotic disease.”(Scarabin, Alhenc-Gelas, Plu-Bureau, Taisne, Agher,Aiach, 1997).

Regular tests & procedures- Blood, especially liver enzymes, are important to assess for the effectiveness of the hormone therapy and monitor for liver damage due to medication and also clotting levels. Initial Thyroid levels are important tests to evaluate, as Hypothyroidism will reduce metabolism and reduce the effects of any hormone therapy.

Prolactin levels should be assessed initially and if a significant amount of nipple discharge is found. This can result in high estrogen doses or recent increases and may signal that the body has passed a safe level of estrogen therapy, this can be adjusted and titrated by an increase in anti-androgen.

Breast cancer risk factors seem tend to be low in comparison to females receiving estrogen replacement therapy. However monthly breast self-exams, and mammograms every 2 years before age 40, then every year thereafter.

How soon do these effects begin? -With effective and continuous dosages, most of the changes to which particular body is genetically prone will start within 2 to 4 months of entering therapy, becoming irreversible within 6 to 12 months, start beginning to level somewhat within 2 years, and be mostly done within approximately 5 years. The leveling generally takes longer if the testes are not removed. Orchiectomy- At 4-5 years, or earlier, of medication therapy the patient should seriously consider surgical castration also called Orchiectomy. This will allow dramatic reduction of the medication and cessation of the anti-androgen.

These timelines are of course generalizations based on what many have typically reported, but do not necessarily mean that everyone will find development, or reversibility, to be within these limits. 

References.

     Toorians AW, Thomassen MC, Zweegman S, Magdeleyns EJ, Tans G, Gooren LJ, Rosing J. Journal of Clinical Endocrinol Metababolism. 2003 Dec;88(12):5723-9. Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people.
Departments of Endocrinology/Andrology, Vrije Universiteit University Medical Center, 1007 MB Amsterdam, The Netherlands. 

   Scarabin, Alhenc-Gelas, Plu-Bureau, Taisne, Agher,Aiach, Effects of Oral and Transdermal Estrogen/Progesterone Regimens on Blood Coagulation and Fibrinolysis in Postmenopausal Women, 1997. Retrieved Feburary 2^nd. 2007 from http://atvb.ahajournals.org/cgi/content/abstract/17/11/3071

   This is a continuing work, which I will be reviewing, also my apologies to F2M’s. You are important and information will be posted shortly.

 Rob Gouldstone Dec. 2007