Hormone replacement therapy (male-to-female)
Hormone replacement therapy (HRT) for
transgenderand transsexualpeople replaces the hormones naturally occurring in their bodies with those of the other sex. However, not all cases of hormone replacement therapy are used by transgendered people. Some reasons for this include men who wish to have a hair-free body, as a result of less of the testosterone, androgens in their body. Its purpose is to cause the development of the secondary sex characteristics of the desired gender. It can not undo the changes produced by the first natural occurring pubertyof transgender people, this is done by sexual reassignment surgeryand for transwomenby epilation. Some intersexpeople also receive HRT, either starting in childhood to confirm the gender they were assigned, or later, if this assignment has proven to be incorrect.
While some people argue that hormonal therapy does not truly masculinize or feminize, the question is one of definitions. If by masculinize and feminize one means to completely reproduce the male or female biological state, that cannot be done with current medical or surgical therapy. However, the goal of HRT, and indeed all somatic treatments, is to provide patients with a more satisfying body that is more congruent with their true psychological gender identity. It should be noted that the effects of hormonal therapy are often much more satisfying to transgender men than transgender women. It is easier to produce secondary male sexual characteristics with androgens than it is to rid transgender women of those established characteristics.
Formal requirements for HRT
The requirements for hormone replacement therapy vary immensely, often at least a certain time of psychological counselling is required, and so is a time of living in the desired gender role, if that is at all possible, in order to assure that they can psychologically function in that gender role. This period is sometimes called the Real Life Experience (RLE). "See also
Standards of care for gender identity disorders."
Some individuals choose to self-administer their medication ("do-it-yourself"), often because available doctors have too little experience in this matter, or no doctor is available in the first place. Sometimes, trans persons choose to self-administer because their doctor will not prescribe hormones without a letter from the patient's therapist stating that the patient meets the diagnostic criteria for GID and is making an informed decision to transition. Many therapists require at least 3 months of continuous psychotherapy and/or a real life test in order to write such a letter as is suggested in the HBIGDA Standards of Care. In these circumstances, the individual may self-administer until they can get these authorizations, feeling that they shouldn't have to wait for a medical professional to be convinced of their situation. In addition, as many individuals must pay for evaluation and care out-of-pocket, expense can also be prohibitive to pursuing such therapy.
However, "self-administration of hormones is potentially dangerous". Individuals seeking physicians who are knowledgeable and willing to treat transgender patients may wish to consult transgender support groups or a directory of LGBT-friendly doctors, in the USA for example the Gay and Lesbian Medical Association's referral service at [http://www.GLMA.org GLMA.org] .
Changes established at puberty
A number of skeletal and
cartilaginouschanges take place after the onset of puberty at various rates and times. Sometime in the late teen years epiphyseal clusure(in other words, the ends of bones are fused closed) takes place and the length of bones is fixed for life. Consequently total height and the length of arms, legs, hands, and feet are not affected by HRT. However, details of bone shape change throughout life, bones becoming heavier and more deeply sculptured under the influence of testosterone. Many of these differences are described in the Desmond Morris book Manwatching.
* Pelvis: The pelvis in females tends to be wider than in males and tilted forward; the pelvis in males tends to be more circular and tilted upwards.
* Hands: Male hands and feet tend to be larger than female hands and feet in persons of equal height.
* Upper Arm: The upper arm in females tends to be significantly longer (about 1") than in males of the same height.
* Head: Females tend to have smaller heads than males of the same height.
* Chest: Female ribcages tend to be narrower than those of males in the same height.
Facial changes develop gradually over time, and sexual dimorphism (physical difference between the sexes) tends to increase with age. Within a population of similar body size and ethnicity:
* Brow: Males tend to develop heavier bony brows than females.
* Cheeks: Female cheeks tend to be fuller and more rounded. Under the influence of estrogen, fat is deposited beneath the skin and overall facial and body contours become softer.
* Nose: The tips of the nasal bones tend to grow more in males than females, creating a larger (longer or wider) nose.
* Jaw: The jaw in males tends to grow wider and more deeply sculptured than in females.
* Larynx: At puberty, the bones and cartilage of the voicebox tend to enlarge less in females than males. In some males, the larynx becomes visible as a bony "adam's apple."
* Lips: Females tend to have thicker, fleshier lips than males of the same size.
For transwomen, taking
estrogens causes among other changes:
* the growth of
breasts, with concomitant enlargement of the nipples, and
* redistribution of body
* thinning of
transgendered people, HRT often includes antiandrogens in addition to the estrogens and progestogens mentioned above.
HRT does not usually cause
facial hairgrowth to be impeded or the voice to change.
* breast development,
* enlarged nipples and areolae
* stretch marks (for some)
* redistribution of body fat,
* significantly reduced
* change in
body odorand sweatproduction,
* less prominence of
* ocular changes,
* gonadal size
psychologicalchanges are harder to define, because HRT is usually the first physical action that takes place when transitioning. This fact alone has a significant psychological impact, which is hard to distinguish from hormonally induced changes. Many also report feeling more confident.
* Absolute: history of estrogen sensitive cancer (for example breast cancer), history of
thromboembolic disease(unless provided with concurrent anti-coagulation therapy), or history of macroprolactinoma.
* Relative: Liver, kidney, or heart disease and stroke (or any of the risk factors for heart disease: high cholesterol, diabetes, obesity, smoking); Strong family history of breast cancer or thromboembolic disease; Gallbladder disease; circulation or clotting conditions such as
peripheral vascular disease, polycythemia vera, sickle cell anaemia, paroxysmal nocturnal hemoglobinuria, hyperlipidemia/ hypercholesterolemia, hyperlipoproteinaemia, hypertension, factor V leiden, prothrombin mutation, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulants, plasminogenor fibrinolysisdisorders, protein C deficiency, protein S deficiency, or antithrombin III deficiency.
Types of therapy
* Doses are often higher than replacement doses for
cisgenderwomen. Usually the dosage is reduced after an orchiectomy(the removal of the testes) or sex reassignment surgery. However, the practice of lowering estrogen doses after such operations has been carried over from the days when very high doses of estrogen were required to decrease testosteronesince anti-androgens were not used. In fact, high doses (though using a less potent estrogen, estradiol, that is endogenousto the human body rather than the risky ethinyl estradioland conjugated estrogens used in the past) are recommended during the first ten or so years of HRTto fully develop, with or without having had an orchiectomy or sex reassignment. After usually ten years or so the dosages can be reduced.
* Many different variations of estradiol exist as well as other types of estrogens although the ones most commonly used are either micronized
estradiol, estradiol acetate, estradiol valerate, estradiol cypionate, estradiol enanthate, conjugated estrogens, esterified estrogens, and ethinyl estradiol.
* Injectable, implanted, nasal, oral, sublingual, gel, and
transdermal patchformulations are available.
* As dosage increases, risks increase as well. Therefore, women with relative contraindications should start at lower doses and increase dosage more gradually.
Progestogensinclude progesteroneand progestins(synthetic analogs of progesterone or 17-alpha hydroxyprogesterone). There are oral, sublingual, suppository, gel, and injectable formulations available.
* Progestogens are involved in the full maturation of the breasts, particularly the mammary structures lobules, acini, and alveoli. [cite journal|author=Orentreich N, Durr NP |year=1974 |month=Jul |title=Mammogenesis in transsexuals |url=http://www.nature.com/jid/journal/v63/n1/full/5617468a.html |journal=Journal of Investigative Dermatology |issue=1 |pages=142–6 |doi= |id= | |volume=63 ] [cite journal |author=Mauvais-Jarvis P, Kuttenn F, Gompel A, Malet C, Fournier S |title= [Estradiol-progesterone interaction in normal and pathological human breast cells] |language=French |journal=Ann. Endocrinol. (Paris) |volume=47 |issue=3 |pages=179–87 |year=1986 |pmid=3535636 |doi= |url=] [cite book|title=New Comprehensive Biochemistry: Hormones and Their Actions, Part I |editor=Cooke BA, King RJB, van der Molen HJ (eds.) |volume=vol. 18a |year=1988 |publisher=Elsevier |location=Amsterdam |pages=] [cite journal|author=Cyrlak D, Wong CH |year=1993 |month=Dec |title=Mammographic changes in postmenopausal women undergoing hormonal replacement therapy |pmid=8249722 |journal=American Journal of Roentgenology |issue=6 |pages=1177–83 |doi= |id= | |volume=161 ] [cite journal|author=Gorins A, Denis C |year=1995 |month= |title=Effects of progesterone and progestational hormones on the mammary gland |pmid=7794024 |journal=Archives d'anatomie et de cytologie pathologiques |issue=1-2 |pages=28–35 |doi= |id= | |volume=43 ] [cite journal|author=Futterweit W |year=1998 |month=Apr |title=Endocrine therapy of transsexualism and potential complications of long-term treatment |pmid=9562902 |journal=Archives of Sexual Behavior |issue=2 |pages=209–26 |doi= |id= | |volume=27 ] [cite book|title=Current Concepts in Transgender Identity |editor=Denny D (ed.) |others=chap. by Basson R, Prior JC |year=1998 |publisher=Garland Publishing |location=New York |pages= |chapter=17. Hormonal Therapy in Gender Dysphoria: The Male-to-Female Transsexual|isbn=081531793X|author=edited by Dallas Denny.|oclc=37156496 ] [cite web |url=http://www2.ulg.ac.be/gynecobs/fc21.html#gbpuber |title=Hormone Dependence of the Mammary Tissue |accessdate= |accessmonthday= June 14 |accessdaymonth= |accessyear=2008 |author= |last=Colin |first=Claude ] [cite journal|author=Shyamala G |year=1999 |month=Jan |title=Progesterone signaling and mammary gland morphogenesis |pmid=10219909 |journal=Journal of Mammary Gland Biology and Neoplasia |issue=1 |pages=89–104 |doi= |id= | |volume=4 ] [cite journal|author=Kanhai RC, Hage JJ et al. |year=2000 |month=Jan |title=Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men |pmid=10632490 |journal=The American Journal of Surgical Pathology |issue=1 |pages=74–80 |doi= |id= | |volume=24 ] [cite journal|author=Schams D, Kohlenberg S et al. |year=2003 |month=May |title=Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution |pmid=12740019 |journal=Journal of Endocrinology |issue=2 |pages=305–17 |doi= |id= | |volume=177 ] [cite journal|author=Lamote I, Meyer E et al. |year=2004 |month=Mar |title=Sex steroids and growth factors in the regulation of mammary gland proliferation, differentiation, and involution |pmid=15072917 |journal=Steroids |issue=3 |pages=145–59 |doi= |id= | |volume=69 ] [cite web |url=http://www.endotext.org/male/male14/male14.htm |title=Gynecomastia: Etiology, Diagnosis, and Treatment |accessdate= |accessmonthday= June 14 |accessdaymonth= |accessyear=2008 |author=Swerdloff RS, Ng J, and Palomeno GE |year=2004 |month=Mar ] [cite journal|author=Baltzell K, Eder S, Wrensch M |year=2005 |month=Jan |title=Breast carcinogenesis: can the examination of ductal fluid enhance our understanding? |pmid=15660141 |journal=Oncology Nursing Forum |issue=1 |pages=33–9 |doi= |id= | |volume=32 ] [cite web |url=http://www.isrec.ch/research/groups/research_groups_detail_eid_1692_lid_2.htm |title=Genetic dissection of signaling pathways important in breast development and breast cancer |accessdate= |accessmonthday= June 14 |accessdaymonth= |accessyear=2008 |author=Brisken C ]
* Progestogens also help fat distribution, increase female libidinal feelings, increase appetite, slight increase in skin oil, increases blood flow to the skin, increases the ability to sweat and lose extra heat, increase in body temperature enabling one to better tolerate the cold, healthier nails, produce a sense of calm and promote sleep, [cite journal|author=Friess E, Tagaya H et al. |year=1997 |month=May |title=Progesterone-induced changes in sleep in male subjects |pmid=9176190 |journal=American Journal of Physiology |issue=5 |pages=E885–91 |doi= |id= | |volume=272 ] [cite journal|author=Montplaisir J, Lorrain J et al. |year=2001 |month=Jan-Feb |title=Sleep in menopause: differential effects of two forms of hormone replacement therapy |pmid=11201509 |journal=Menopause |issue=1 |pages=10–6 |doi= |id= | |volume=8 ] [cite journal|author=Söderpalm AH, Lindsey S et al. |year=2004 |month=Apr |title=Administration of progesterone produces mild sedative-like effects in men and women |pmid=14644065 |journal=Psychoneuroendocrinology |issue=3 |pages=339–54 |doi= |id= | |volume=29 ] [cite journal|author=van Broekhoven F, Bäckström T, Verkes RJ |year=2006 |month=Nov |title=Oral progesterone decreases saccadic eye velocity and increases sedation in women |pmid=17034954 |journal=Psychoneuroendocrinology |issue=10 |pages=1190–9 |doi= |id= | |volume=31 ] and increase energy. Progesterone in particular is essential for bone health and seems to have a role in skin elasticity, and
nervetissue. Other effects that have been seen with progesterone in particular (not the synthetics) include reducing spasms and relaxing smooth muscletone, gallbladderactivity is reduced, bronchiare widened (helps respiration) [cite journal|author=Golparvar M, Ahmadi F, Saghaei M |year=2005 |month=Jan |title=Effects of progesterone on the ventilatoryperformance in adult trauma patients during partial support mechanical ventilation |url=http://www.ams.ac.ir/AIM/0581/008.pdf |journal=Archives of Iranian Medicine |issue=1 |pages=27–31 |doi= |id= | |volume=8 ] , an anti-inflammatory agent and reduces the immune response, normalizing blood clottingand vascular tone, zincand copperlevels, cell oxygen levels, and use of fat stores for energy. Progesterone also assists in thyroidfunction and bone building by osteoblasts. However, progestogens may increase skin oil and libido too much for some and there may be acne breakouts due to the increase in skin oil.
Spironolactoneis the most frequently used anti-androgen in the United States because it is relatively safe and inexpensive. Cyproterone acetateis more commonly used outside of the US.
* Spironolactone is a 'potassium sparing diuretic' that is also used to treat low-renin hypertension, edema,
hyperaldosteronism, and low potassium levels caused by other diuretics. It can cause high potassium levels, hyperkalemia, and is therefore contra-indicated in people with renal failure or who otherwise have elevated potassium levels. Spironolactone prevents the formation of testosterone in the testis (though not in the adrenals) by inhibiting enzymes involved in its production [cite journal|author=Menard RH, Stripp B, Gillette JR |year=1974 |month=Jun |title=Spironolactone and testicular cytochrome P-450: decreased testosterone formation in several species and changes in hepatic drug metabolism |pmid=4831127 |journal=Endocrinology |issue=6 |pages=1628–36 |doi= |id= | |volume=94 ] [cite journal|author=Stripp B, Taylor AA et al. |year=1975 |month=Oct |title=Effect of spironolactone on sex hormones in man |pmid=1176584 |journal=The Journal of Clinical Endocrinology and Metabolism |issue=4 |pages=777–81 |doi= |id= | |volume=41 ] [cite journal|author=Pozzi AG, Ceballos NR |year=2000 |month=Aug |title=Human chorionic gonadotropin-induced spermiation in Bufo arenarum is not mediated by steroid biosynthesis |pmid=10936036 |journal=General and Comparative Endocrinology |issue=2 |pages=164–71 |doi= |id= | |volume=119 ] [cite journal|author=Canosa LF, Ceballos NR |year=2001 |month=Aug |title=Effects of different steroid-biosynthesis inhibitors on the testicular steroidogenesis of the toad Bufo arenarum |pmid=11585264 |journal=Journal of Comparative Physiology |issue=6 |pages=519–26 |doi= |id= | |volume=171 ] and is an androgen receptor antagonist(prevents androgens from binding to androgen receptors).cite journal |author=Boisselle A, Dionne FT, Tremblay RR|title=Interaction of spironolactone with rat skin androgen receptor|journal=Canadian Journal of Biochemistry|year=July 1979|volume=57|issue=7|pages=1042–6 |pmid=487244] cite journal |author=Yamasaki K, Sawaki M et al.|title=Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals|journal=Toxicology|year=February 2004|volume=195|issue=2-3|pages=177–86 |pmid=14751673 |doi=10.1016/j.tox.2003.09.012]
Cyproteroneacetate is derived from 17-alpha hydroxyprogesterone and suppresses luteinizing hormone(which in turn reduces testosterone levels), blocks androgens from binding to androgen receptors, and is a weak progestin. It has been used to treat prostate cancer. If used long-term in dosages of 150 milligrams or higher it can possibly lead to liver damage or failure. [cite journal|author=Kaiser E, Gruner HS |year=1987 |month= |title=Liver structure and function during long-term treatment with cyproterone acetate |pmid=2955749 |journal=Archives of Gynecology |issue=4 |pages=217–23 |doi= |id= | |volume=240 ] [cite journal|author=Willemse PH, Dikkeschei LD et al. |year=1988 |month=Mar |title=Clinical and endocrine effects of cyproterone acetate in postmenopausal patients with advanced breast cancer |pmid=2968261 |journal=European Journal of Cancer & Clinical Oncology |issue=3 |pages=417–21 |doi= |id= | |volume=24 ] [cite journal|author=Hinkel A, Berges RR et al. |year=1996 |month= |title=Cyproterone acetate in the treatment of advanced prostatic cancer: retrospective analysis of liver toxicity in the long-term follow-up of 89 patients |pmid=8977068 |journal=European Urology |issue=4 |pages=464–70 |doi= |id= | |volume=30 ] [cite journal|author=Watanabe S, Cui Y et al. |year=1997 |month=Sep |title=Follow-up study of children with precocious puberty treated withcyproterone acetate |pmid=9337516 |journal=Journal of Epidemiology |issue=3 |pages=173–8 |doi= |id= | |volume=7 ] [cite journal|author=Migliari R, Muscas G et al. |year=1999 |month=Dec |title=Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy |pmid=9337516 |journal=The Italian Archives of Urology, Andrology |issue=5 |pages=293–302 |doi= |id= | |volume=71 ] [cite journal|author=Laron Z, Kauli R |year=2000 |month=Jul |title=Experience with cyproterone acetate in the treatment of precocious puberty |pmid=10969925 |journal=Journal of Pediatric Endocrinology & Metabolism |issue=Suppl 1 |pages=805–10 |doi= |id= | |volume=13 ] [cite journal|author=Giordano N, Nardi P et al. |year=2001 |month=Sep |title=Acute hepatitis induced by cyproterone acetate |pmid=11573856 |journal=The Annals of Pharmacotherapy |issue=9 |pages=1053–5 |doi= |id= | |volume=35 ] [cite journal|author=Lin AD, Chen KK et al. |year=2003 |month=Dec |title=Antiandrogen-associated hepatotoxicity in the management of advanced prostate cancer |pmid=15015823 |journal=Journal of the Chinese Medical Association |issue=12 |pages=735–40 |doi= |id= | |volume=66 ] [cite journal|author=Savidou I, Deutsch M et al. |year=2006 |month=Dec |title=Hepatotoxicity induced by cyproterone acetate: a report of three cases |pmid=17167851 |journal=World Journal of Gastroenterology |issue=46 |pages=7551–5 |doi= |id= | |volume=12 ]
* Other anti-androgens include
bicalutamide, flutamide, and nilutamide. Unlike the two medications above, these do not lower testosterone levels but rather prevent testosterone and dihydrotestosterone from binding to androgen receptors. Because these have a weak action at the brain they do not lower libido or decrease erections. Two other anti-androgens that are rarely prescribed are ketoconazoleand cimetidine. Ketoconazole has been used in those with prostatic cancerand hirsutism. Cimetidine has also been used in hirsutism. Ketoconazole has the potential of liver toxicity over long-term use and cimetidine is a relatively weak anti-androgen.
* Certain anti-androgens do not lower testosterone levels or prevent its action upon tissues but rather its metabolite, dihydrotestosterone (DHT), from forming. These medications can be used when the patient has male-pattern hair loss (
androgenetic alopecia) and/or an enlarged prostate ( benign prostatic hyperplasia). DHT contributes to the manifestation and exacerbation of both. Two medications are currently available to prevent the creation of DHT, finasterideand dutasteride. DHT levels can be lowered up to approximately 60-75% with the former depending upon dosage and up to 93-94% with the latter.
* In both sexes, the hypothalamus releases GnRH (
gonadotropin-releasing hormone) to stimulate the pituitaryto produce LH ( luteinizing hormone) and FSH ( follicle-stimulating hormone) which in turn cause the gonads to produce sex steroids. In adolescents of either sex with relevant indicators, GnRH agonists, such as goserelin acetate can be used to suspend the advance of sex steroid-induced, inappropriate pubertal changes for a period without inducing any changes in the gender-appropriate direction. GnRH agonists work by initially over stimulating the pituitary then rapidly desensitizing it to the effects of GnRH. After an initial surge, over a period of weeks, gonadal androgen production is greatly reduced. There is considerable controversy over the earliest age, and for how long it is clinically, morally and legally safe to do this. The current, sixth edition of the Harry Benjamin International Gender Dysphoria AssociationStandards of Care permit from Tanner stage2, but do not allow the addition of gender-appropriate hormones until 16, which could be five or more years. The sex steroids do have important other functions. Also skeletal growth, which is often considered to be masculinising, is not hindered by GnRH agonists.
* GnRH agonists are often prescribed to prevent the reactivation of testicular function where surgeons require the cessation of estrogens prior to surgery.
* The high cost of GnRH agonists is often a significant factor.
* The most significant cardiovascular risk for transgender women is the pro-thrombotic effect of estrogens (Increased blood clotting.) This manifests most significantly as an increased risk for thromboembolic disease:
deep venous thrombosis(DVT) and pulmonary embolism(PE) which occurs when DVTs break off and migrate through the venous system to the lungs. It is important for any person on female hormones to immediately seek medical care if she develops pain or swelling of one leg (especially calf) as this is the predominant symptom of a DVT, or if she develops symptoms of PE: chest pain, shortness of breath, fainting, or palpitations (even without leg pain or swelling).
* In practice this becomes very important to transgender women undergoing surgery. Ethinyl and conjugated oral estrogens should be withheld for a week before and until two weeks after surgery.
* DVTs occur more frequently in the first year of treatment with estrogens. However this may represent a 'screening by treatment' of patients who may have genetic predispositions to thromboembolic disease, with those who are "more likely to develop DVTs" doing so early on in therapy. However, if patients have a family history of thromboembolic disease, screening for known disease may be appropriate.
* DVT risk is higher with oral estrogen (particularly ethinyl estradiol and conjugated estrogens) rather than injectable, transdermal, implantable, and nasal estrogens. [cite journal|author=Henriksson P, Eriksson A et al. |year=1988 |month= |title=Cardiovascular follow-up of patients with prostatic cancer treated with single-drug polyestradiol phosphate |pmid=3211807 |journal=Prostate |issue=3 |pages=257–61 |doi= |id= | |volume=13 ] [cite journal|author=von Schoultz B, Carlström K et al. |year=1989 |month= |title=Estrogen therapy and liver function--metabolic effects of oral and parenteral administration |pmid=2664738 |journal=Prostate |issue=4 |pages=389–95 |doi= |id= | |volume=14 ] [cite journal|author=Aro J, Haapiainen R et al. |year=1990 |month= |title=The effect of parenteral estrogen versus orchiectomy on blood coagulation and fibrinolysis in prostatic cancer patients |pmid=2178941 |journal=European Urology |issue=2 |pages=161–5 |doi= |id= | |volume=17 ] [cite journal|author=Henriksson P, Blombäck M et al. |year=1990 |month=Mar |title=Effect of parenteral oestrogen on the coagulation system in patients with prostatic carcinoma |pmid=2110842 |journal=British Journal of Urology |issue=3 |pages=282–5 |doi= |id= | |volume=65 ] [cite journal|author=Aro J |year=1991 |month= |title=Cardiovascular and all-cause mortality in prostatic cancer patients treated with estrogens or orchiectomy as compared to the standard population |pmid=2006119 |journal=Prostate |issue=2 |pages=131–7 |doi= |id= | |volume=18 ] [cite journal|author=Henriksson P, Stege R |year=1991 |month= |title=Cost comparison of parenteral estrogen and conventional hormonal treatment in patients with prostatic cancer |pmid=1907600 |journal=International Journal of Technology Assessment in Health Care |issue=2 |pages=220–5 |doi= |id= | |volume=7 ] [cite journal|author=Henriksson P |year=1991 |month=Jan-Feb |title=Estrogen in patients with prostatic cancer. An assessment of the risks and benefits |pmid=2029353 |journal=Drug Safety |issue=1 |pages=47–53 |doi= |id= | |volume=6 ] [cite journal|author=Caine YG, Bauer KA et al. |year=1992 |month=Oct |title=Coagulation activation following estrogen administration to postmenopausal women |pmid=1333098 |journal=Thrombosis and Haemostasis |issue=4 |pages=392–5 |doi= |id= | |volume=68 ] [cite journal|author=Stege R, Sander S |year=1993 |month=Mar |title=Endocrine treatment of prostatic cancer. A renaissance for parenteral estrogen |pmid=8480286 |journal=Tidsskrift for den Norske laegeforening |issue=7 |pages=833–5 |doi= |id= | |volume=113 ] [cite journal|author=Stege R, Carlström K et al. |year=1995 |month=Sep |title=Intramuscular depot estrogens (Estradurin) in treatment of patients with prostate carcinoma. Historical aspects, mechanism of action, results and current clinical status |pmid=7483157 |journal=Der Urologe. Ausg. A |issue=5 |pages=398–403 |doi= |id= | |volume=34 ] [cite journal|author=Cox RL, Crawford ED |year=1995 |month=Dec |title=Estrogens in the treatment of prostate cancer |pmid=7500443 |journal=Journal of Urology |issue=6 |pages=1991–8 |doi= |id= | |volume=154 ] cite journal |author=Henriksson P, Carlström K et al.|title=Time for revival of estrogens in the treatment of advanced prostatic carcinoma? 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Oncology|year=2006|volume=3|issue=10|pages=552–63|pmid=17019433 |doi=10.1038/ncponc0602] cite journal |author=Basurto L, Saucedo R et al.|title=Effect of pulsed estrogen therapy on hemostatic markers in comparison with oral estrogen regimen in postmenopausal women|journal=Gynecologic and Obstetric Investigation|year=2006|volume=61|issue=2|pages=61–4|pmid=16192735 |doi=10.1159/000088603] cite journal |author=Hemelaar M, Rosing J et al.|title=Less effect of intranasal than oral hormone therapy on factors associated with venous thrombosis risk in healthy postmenopausal women|journal=Arteriosclerosis, Thrombosis, and Vascular Biology|year=July 2006|volume=26|issue=7|pages=1660–6|pmid=16645152 |doi=10.1161/01.ATV.0000224325.96659.53] cite journal |author=Hedlund PO, Damber JE et al.|title=Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5|journal=Scandinavian Journal of Urology and Nephrology|year=2008|volume=42|issue=3|pages=220–9|pmid=18432528 |doi=10.1080/00365590801943274] cite journal |author=Canonico M, Plu-Bureau G, et al.|title=Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis|journal=British Medical Journal|year=May 2008|volume=336|issue=7655|pages=1227–31|pmid=18495631 |doi=10.1136/bmj.39555.441944.BE]
* DVT risk also increases with age and with smoking, so many clinicians advise using the safer estrogen formulations in patients who smoke or are older than age 40.
* If screening is undertaken for known pro-thrombotic mutations such as Factor V-Leiden, antithrombin III, and protein C or S deficiency, it should be done so to "increase the safety" of hormonal therapy and not as a screen for who may undertake hormonal therapy. Given that the risk of warfarin treatment in a relatively young, well-informed, and otherwise healthy population is quite low and that the risk of adverse physical and psychological outcome for untreated transgender patients is high, a prothrombotic mutation is not an absolute contraindication for hormonal therapy. (See: Levy, et al “Endocrine Intervention for Transsexuals” Clin Endo 2003. 59:409-418.)
* The antiandrogen bicalutamide is associated with an increased risk of heart failure when used as monotherapy (without any other drugs). [cite web |url=http://www.casodex.net/gUserFiles/Casodex150mgmonograph.pdf |title=Casodex monograph |accessdate= |accessmonthday= June 14 |accessdaymonth= |accessyear=2008 ] A study of prostate cancer patients also showed an increased number of deaths unrelated to cancer among patients taking 150mg/day bicalutamide. [cite journal|author=Iversen P, Johansson JE et al. |year=2004 |month=Nov |title=Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6 |pmid=15540741 |journal=Journal of Urology |issue=5 |pages=1871–6 |doi= |id= | |volume=172 ] This prompted Health Canada to withdraw its approval for 150mg bicalutamide as monotherapy. [cite web |url=http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/public/_2003/casodex_pa-ap-eng.php |title=Important Safety Information Regarding Casodex 150 mg |accessdate= |accessmonthday= June 14 |accessdaymonth= |accessyear=2008 ] The increased death rate has not been observed where bicalutamide was combined with a method of reducing androgen production. The exact reasons for the heart failure and deaths have not been completely determined, however a likely cause is acute
adrenal insufficiencyand hypotensiondue to the action of DHT [cite journal |author=Rossi R, Zatelli MC, Valentini A, "et al" |title=Evidence for androgen receptor gene expression and growth inhibitory effect of dihydrotestosterone on human adrenocortical cells |journal=J. Endocrinol. |volume=159 |issue=3 |pages=373–80 |year=1998 |month=Dec|pmid=9834454 |doi= |url=http://joe.endocrinology-journals.org/cgi/pmidlookup?view=long&pmid=9834454] during episodes of bicalutamide withdrawal. Because bicalutamide is extremely lipophilic, it is difficult to avoid periods of low serum concentration due to the uptake of bicalutamide into fat cells.
* Current facial hair is only slightly affected (some reduction in density, coverage, and slower growth) by anti-androgens. Those who are less than a decade past puberty and/or whose ethnicity generally lacks a significant amount of facial hair will have better results with anti-androgens. Those taking anti-androgens will have better results with electrolysis/
laser hair removalthan those who are not. If one is still in their teens or early twenties, there will be prevention of new facial hairs from developing if testosterone levels are within the female range.cite web|url=http://www.transgendercare.com/medical/hormonal/hormone-tx_assch_gooren.htm |title=Hormone Treatment in Transsexuals | accessmonthday= June 13 |accessdaymonth= |accessyear=2008 |month= |year=1992 |author=Asscheman H, Gooren LJ] cite journal|author=Giltay EJ, Gooren LJ |year=2000 |month=Aug |title=Effects of sex steroid deprivation/administration on hair growth and skin sebum production in transsexual males and females |pmid=10946903 |journal=Journal of Clinical Endocrinology and Metabolism |issue=8 |pages=2913–21 |doi= |id= | |volume=85 ]
* Body hair (chest, periareolar, shoulders, back, abdomen, rear, thighs, tops of hands, tops of feet) will, over time, turn from terminal ("normal") hairs to
vellushairs (very tiny, blonde "baby" hairs). Hair on the arms, perianal, and perinealwill reduce but may not turn to vellus hair on the latter two regions (some natal females also have some hair in these areas). Underarm hair will slightly change in texture and length, pubic hair becomes more typically female in pattern. Lower leg hair becomes less dense in concentration. All depend upon genetics.
* Head hair may slightly change in texture, curl, and color (new hairs that is, not hair that has already formed and reached the surface prior to HRT), this is especially likely with hair growth from previously bald areas.
* Eyebrow hair becomes less "bushy" or scattered.
*Transgender women report a sometimes significant reduction in
libidoall depending upon the dosage of anti-androgens. A small number of post-operative transsexual women may take small amounts of testosterone to boost the libido. Many pre-operative transsexual women simply wait until after sex-reassignment surgery to begin an active sex life (due to how they feel towards their genitals and/or, for heterosexual or bisexual transsexual women, an aversion to anal sex) and for newly post-operative women how satisfied they are with the results. Raising estrogen dosage or adding a progestogen has also raised the libido of some transwomen.
*Spontaneous and morning erections decrease in frequency significantly, however some who have had an
orchiectomystill experience morning erections. Voluntary erections can be maintained since the brain is the most important sex organ, a developed repertoire of fantasies and good visualization is a must. It also depends on how one views their own genitals (disgust, strong aversion to, tolerable, etc.).
*Testi volume is reduced by about 25% with typical dosages and as much as 50% in higher dosages, especially after a year of HRT.This is in response to the decrease in
Leydig cells, Sertoli cells, and interstitial tissue, which produce both spermand testosterone. When testosterone is dramatically reduced spermatogenesisis halted almost completely, when the cells that are involved in these processes go unused they atrophy (shrink).
*The line that runs down the underside of the
penisand down the middle of the scrotum, the peno-scrotalraphe (where the urogenital folds fused early in the womb), will darken.
water retentionis likely
* Childbearing, as experienced by
cisgenderwomen, is impossible with today's technology. Pre-operative sperm banking can be done, however, allowing artificial inseminationto be used to produce genetic offspring with someone else at a later date. Medical advances in the near future may one day make this possible by using a donor uteruslong enough to carry a child to term as anti-rejection drugs do not seem to affect the fetus. [ [http://www.saukvalley.com/articles/2007/01/23/features/health_and_medical/288035642038177.txt Doctors plan uterus transplants to help women with removed, damaged wombs have babies] - Associated Press] cite journal |author=Fageeh W, Raffa H et al.|title=Transplantation of the human uterus|journal=International Journal of Gynaecology and Obstetrics|year=March 2002|volume=76|issue=3|pages=245–51|pmid=11880127 |doi=10.1016/S0020-7292(01)00597-5] cite journal |author=Del Priore G, Stega J et al.|title=Human uterus retrieval from a multi-organ donor|journal=Obstetrics and Gynecology|year=January 2007|volume=109|issue=1|pages=101–4|pmid=17197594] cite journal |author=Nair A, Stega J et al.|title=Uterus Transplant: Evidence and Ethics|journal=Annals of the New York Academy of Sciences|year=April 2008|volume=1127|pages=83–91|pmid=18443334 |doi=10.1196/annals.1434.003] The DNAin a donated ovumcan be removed and replaced with the DNA of the receiver. Further in the future stem cell biotechnology may also make this possible, with no need for anti-rejection drugs.
estrogens and androgens are necessary in both biological males and females for healthy bone. (Young healthy women produce about 10 mg of testosterone monthly. Higher bone mineral density in males is associated with higher serum estrogen.)
* Bone is not static. It is constantly being reabsorbed and created. Osteoporosis results when bone formation occurs at a rate less than bone reabsorption.
* Estrogen is the predominant sex hormone that slows bone loss (even in men.)
* Both estrogen and testosterone help stimulate bone formation (T, especially at puberty.)
* The hips will rotate slightly forward due to changes in the tendons so hip discomfort is not uncommon.
* Any drug can cause adverse reactions with other medications so it is wise to check with a doctor or pharmacist when starting any new medication.
* Of the estrogen formulations commonly used, ethinyl estradiol (commonly found in birth control pills) has the greatest number of adverse reactions.
* The uppermost layer of skin, the
stratum corneum, becomes thinner and therefore more translucent and pinkish (spider veins may appear or be more noticeable), less collagen, more susceptible to tearing and irritation from scratching or shaving, increased tactile sensation, and slightly lighter in color due to a slight decrease in melanin (pigment).
* Skin becomes softer
Sebaceous glandactivity (which is triggered by androgens) lessens which lowers the amount of sebum(oil) production on the skin and scalp, consequently the skin becomes less prone to the formation of acne due to the less quantity of oil that is produced. Dry skin becomes a problem and lotions and oils may be necessary.
* The skin's pores become smaller due to the low quantities of sebum produced
* Body odor (skin, sweat, and urine) will become less "metallic," "sharp," or "acrid" and more "sweet" and "musky."
apocrine glands(type of sweat glands) become inactive and body odor decreases. Sebum also contributes to body odor, the production of which is reduced by anti-androgens (as described above).
subcutaneous(under skin) adipose(fat) tissue accumulates. This gives a more puffy/softer appearance. Consequently dimpling, or cellulite, will be more apparent on the thighs and buttocks due to this along with the thinness of the skin.
* Susceptibility to sunburn increases possibly due to the thinner skin and/or less skin pigment.
* Because of the increase in adipose tissue in the hips, thighs, and rear,
stretch marks(striae distensae) may appear on the skin in these areas.
* The lens of the eyes changes in curvature
* Due to decreased androgens, the
meibomian glands (aka., tarsal, palpebral, or tarsoconjunctival glands. A type of sebaceous gland on the upper and lower eyelids that open at the edges of the lids) produce less oil (oil that makes up the lipid layer of tear film which prevents the evaporation of the watery layer beneath) and a tendency for dry eyes may be a problem.cite journal |author=Krenzer KL, Dana MR et al.|title=Effect of androgen deficiency on the human meibomian gland and ocular surface|journal=Journal of Clinical Endocrinolgy and Metabolism|year=December 2000|volume=85|issue=12|pages=4874–4882|pmid=11134156 |doi=10.1210/jc.85.12.4874] cite journal |author=Sullivan DA, Sullivan BD et al.|title=Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye|journal=Annals of the New York Academy of Sciences|year=June 2002|volume=966|pages=211–222|pmid=12114274] cite journal |author=Sullivan BD, Evans JE|title=Complete androgen insensitivity syndrome: effect on human meibomian gland secretions|journal=Archives of Ophthalmology|year=December 2002|volume=120|issue=12|pages=1689–1699|pmid=12470144] cite journal |author=Cermak JM, Krenzer KL et al.|title=Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?|journal=Cornea|year=August 2003|volume=22|issue=6|pages=516–521|pmid=12883343 |doi=10.1097/00003226-200308000-00006] cite journal |author=Oprea L, Tiberghien A et al.|title=Hormonal regulatory influence in tear film|journal=Journal francais d'ophtalmologie|year=October 2004|volume=27|issue=8|pages=933–941|pmid=15547478 |doi=10.1016/S0181-5512(04)96241-9] There are reports of eye color slightly lightening. Though this has no studies.
* Sensitivity to male body odor(s) (including male pheromones) may be positively correlated with elevated estrogen levels. Overall, olefactory senses may increase. Progestogens, however, often lowers the sensitivity to male pheromones.
Mammary gland development
Breast, nipple, and areolar development takes 4-6 years to complete depending upon genetics, and sometimes as long as 10 years. It is normal for there to be a "stall" in breast growth during feminization, or for the size of one breast to be a little bigger than the other. MtF who undergo HRToften experience breast development which is below the comparable natal femalenorm (many seek breast augmentation); it is rare for a HRT patient to opt for breast reduction. The size of the rib cage and shoulder width also play a role in the perceivable "size" of the breasts; both characteristics are usually smaller than in natal females, i.e., if a natal female and a transsexual female were to have the same cup size, the transsexual female's breasts would most likely appear smaller. Thus when a transwomanopts to have breast augmentation, the implantsused are, on the average, larger than those commonly used by natal females.
* The nipples will become more sensitive to
Adipose tissue distribution
* Fat distribution in the body slowly changes over months and years. The body will now tend to accumulate new adipose tissue (fat) in a typically female pattern. This includes the hips, thighs, rear, pubis, upper arms, and breasts. The body will now tend to use/burn the old adipose tissue in the waist making the waist appear smaller as well as on the shoulders and back.
* Subcutaneous adipose tissue increases in the face (cheeks and lips) making the face appear puffier, appears to "round out" the face, and the face appears less "drawn" or "hollow" with slightly less emphasis on the jaw due to the lower portion of the cheeks having filled in.
* Estrogens may predispose to gallbladder disease - especially in older and obese people
* Estrogens (especially oral forms) may cause elevations in transaminases (liver function tests) indicating liver toxicity. LFTs should therefore be periodically monitored in transgender women
* Mood changes can occur - including the development of depression, particularly in those who take
* Migraines can be made worse or unmasked by estrogen therapy
* Estrogens can induce the development of prolactinomas, which is why prolactin levels should periodically be monitored in transgender women. Milk discharge from the nipples can be a sign of elevated prolactin levels. If a prolactinoma becomes large enough, it can cause visual changes (especially decreased peripheral vision), headaches, mood changes, depression, dizziness, nausea, vomiting, and symptoms of pituitary failure like
* Recent studies have indicated that cross-hormone therapy in transwomen may result in a reduction in brain volume towards female proportions.cite journal|author=Hulshoff, Cohen-Kettenis et al. |year=2006 |month=Jul |title=Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure |url=http://www.eje-online.org/cgi/content/abstract/155/suppl_1/S107 |journal=European Journal of Endocrinology |issue=Suppl 1 |pages=107–114 |doi=10.1530/eje.1.02248 |id=ISSN|0804-4643 | |volume=155 ] It should be noted that brain volume has nothing to do with
* Estrogen therapy causes decreased insulin sensitivity which places transgender women at increased risk of developing type II diabetes.
* One's metabolism slows down and one tends to gain weight, lose energy, need more sleep, and become cold more easily. Due to androgen deprivation a loss of muscle tone, a slower metabolism, and physical weakness becomes more evident. Building muscle will take twice as much work as before. However, the addition of a progestogen may increase energy although an increase in appetite may be seen as well.
Hormone replacement therapy (female-to-male)
* [http://www.tg2tg.org/forums/lifestyles/therapy/mtf-faq.htm MtF Hormone FAQ]
* [http://www.dph.sf.ca.us/chn/HlthCtrs/HlthCtrDocs/TransGendprotocols.pdf Tom Waddell Clinic Transgender Protocol] - MTF and FTM clinical protocols aimed at providers
* [http://www.tsroadmap.com Transsexual Road Map] - Making informed decisions and setting realistic, achievable transition goals
*cite journal |author=Moore E, Wisniewski A, Dobs A |title=Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue=8 |pages=3467–73 |year=2003 |month=Aug |pmid=12915619 |doi= |url=http://jcem.endojournals.org/cgi/content/full/88/8/3467
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