Hormone replacement therapy (male-to-female)
Encyclopedia
Hormone replacement therapy (HRT) for transgender
and transsexual people changes the balance of sex hormone
s in their bodies. Some intersex
people also receive HRT, either starting in childhood to confirm the sex to which they were assigned, or later, if this assignment has proven to be incorrect. Some men may use HRT to have a hair-free body, as a result of less testosterone
in their bodies..
Its purpose is to cause the development of the secondary sex characteristic
s of the desired sex
. It cannot undo the changes produced by the first natural occurring puberty
, which necessitates sexual reassignment surgery and epilation
by either electrolysis
and/or laser hair removal
. The effects of hormonal therapy are often much more satisfying to trans men than trans women, as it is easier to produce secondary male sexual characteristics with androgens than it is to rid trans women of those established characteristics.
.
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 three 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 and orally delivered hormones can cause liver damage.
s causes among other changes:
For male-to-female transgender
ed people, HRT often includes antiandrogen
s in addition to the estrogen
s and progestogens mentioned above.
HRT does not usually cause facial hair
growth to be impeded or the voice
to change.
The psychological changes are harder to define, because HRT is usually the first physical action that takes place when transitioning. Thus, the act itself of beginning HRT has a significant psychological effect, which is hard to distinguish from hormonally induced changes.
Transgender
Transgender is a general term applied to a variety of individuals, behaviors, and groups involving tendencies to vary from culturally conventional gender roles....
and transsexual people changes the balance of sex hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s in their bodies. Some intersex
Intersex
Intersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
people also receive HRT, either starting in childhood to confirm the sex to which they were assigned, or later, if this assignment has proven to be incorrect. Some men may use HRT to have a hair-free body, as a result of less testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
in their bodies..
Its purpose is to cause the development of the secondary sex characteristic
Secondary sex characteristic
Secondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...
s of the desired sex
Sex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
. It cannot undo the changes produced by the first natural occurring puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, which necessitates sexual reassignment surgery and epilation
EPilation
EPilation is the first full-length release from Brisbane musician Tara Simmons. Although a full-length, EPilation contains no new material and is a compilation of Tara's first two EPs Pendulum and All The Amendments...
by either electrolysis
Electrolysis
In chemistry and manufacturing, electrolysis is a method of using a direct electric current to drive an otherwise non-spontaneous chemical reaction...
and/or laser hair removal
Laser hair removal
Laser hair removal was performed experimentally for about 20 years before it became commercially available in the mid 1990s. One of the first published articles describing laser hair removal was authored by the group at Massachusetts General Hospital in 1998...
. The effects of hormonal therapy are often much more satisfying to trans men than trans women, as it is easier to produce secondary male sexual characteristics with androgens than it is to rid trans 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 counseling is required. Some organizations still require a period of time living as the desired gender role. This period is sometimes called the Real Life Experience (RLE). People from the transgender community say that RLE is psychologically harmful and is a form of "gatekeeping" - barring the person from transitioning for as long as possible, if not permanently. See also Standards of care for gender identity disordersStandards of care for gender identity disorders
The Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People are non-binding protocols outlining the usual treatment for individuals who wish to undergo hormonal or surgical transition to the other sex...
.
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 three 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
Out-of-pocket expenses
Out-of-pocket expenses are direct outlays of cash which may or may not be later reimbursed.In operating a vehicle, gasoline, parking fees and tolls are considered out-of-pocket expenses for the trip...
, expense can also be prohibitive to pursuing such therapy.
However, self-administration of hormones is potentially dangerous and orally delivered hormones can cause liver damage.
Changes established at puberty
A number of skeletal and cartilaginous changes take place after the onset of puberty at various rates and times. Sometime in the late teen years epiphyseal closure (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.Changes
For transwomen, taking estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s causes among other changes:
- The growth of breastBreastThe breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
s, with concomitant enlargement of the nipples. - Redistribution of body fatFatFats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
. - Thinning of skinSkin-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
.
For male-to-female transgender
Transgender
Transgender is a general term applied to a variety of individuals, behaviors, and groups involving tendencies to vary from culturally conventional gender roles....
ed people, HRT often includes antiandrogen
Antiandrogen
Antiandrogens, or androgen antagonists, first discovered in the 1960s, prevent androgens from expressing their biological effects on responsive tissues. Antiandrogens alter the androgen pathway by blocking the appropriate receptors, competing for binding sites on the cell's surface, or affecting...
s in addition to the estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s and progestogens mentioned above.
HRT does not usually cause facial hair
Facial hair
Facial hair is a secondary sex characteristic of human males. Men often start developing facial hair in the later years of puberty or adolescence, approximately between 17–20 years of age, and most do not finish developing a fully adult beard until their early 20s or even later...
growth to be impeded or the voice
Human voice
The human voice consists of sound made by a human being using the vocal folds for talking, singing, laughing, crying, screaming, etc. Its frequency ranges from about 60 to 7000 Hz. The human voice is specifically that part of human sound production in which the vocal folds are the primary...
to change.
Irreversible changes
- Breast development
- Enlarged nipples and areolae
- Stretch marks (for some)
Reversible changes
- Decreased libidoLibidoLibido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
- Redistribution of body fat
- Reduced muscleMuscleMuscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
development - Various skinSkin-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
changes - Significantly reduced body hair
- Change in body odorBody odorBody odor or body odour, sometimes colloquially abbreviated as B.O., is the smell of bacteria growing on the body. The bacteria multiply rapidly in the presence of sweat, but sweat itself is almost completely odorless to humans....
and sweatSWEATSWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...
production - Less prominence of veins
- Ocular changes
- Reduced gonadal size
The psychological changes are harder to define, because HRT is usually the first physical action that takes place when transitioning. Thus, the act itself of beginning HRT has a significant psychological effect, which is hard to distinguish from hormonally induced changes.
Contraindications
- 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 veraPolycythemia veraPolycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
, sickle cell anaemia, paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...
, hyperlipidemiaHyperlipidemiaHyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
/hypercholesterolemiaHypercholesterolemiaHypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
, hyperlipoproteinaemia, hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, factor V leidenFactor V LeidenFactor V Leiden is the name given to a variant of human factor V that causes a hypercoagulability disorder. In this disorder the Leiden variant of factor V cannot be inactivated by activated protein C. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst Eurasians...
, prothrombin mutation, antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulantLupus anticoagulantLupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. It is important to note that this disease name is actually a misnomer...
s, plasminogen or fibrinolysisFibrinolysisFibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
disorders, protein C deficiencyProtein C deficiencyProtein C deficiency is a rare genetic trait that predisposes to thrombotic disease. It was first described in 1981. The disease belongs to a group of genetic disorders known as thrombophilias. The prevalence of protein C deficiency has been estimated to about 0.2% to 0.5% of the general population...
, protein S deficiencyProtein S deficiencyProtein S deficiency is a disorder associated with increased risk of venous thrombosis. Protein S, a vitamin K-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activated protein C in the proteolytic degradation of factor Va and factor VIIIa...
, or antithrombin III deficiencyAntithrombinAntithrombin is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites...
.
Estrogens
- Doses are often higher than replacement doses for women. Usually the dosage is reduced after an orchiectomy (the removal of the testes) or sex reassignment surgerySex reassignment surgerySex reassignment surgery is a term for the surgical procedures by which a person's physical appearance and function of their existing sexual characteristics are altered to resemble...
. 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 testosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
since anti-androgens were not used. In fact, high doses (though using a less potent estrogen, estradiol, that is endogenousEndogenousEndogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
to the human body rather than the risky ethinyl estradiol and conjugated estrogensPremarinPremarin is the commercial name for a compound cream of vaginally administered estrogens, consisting primarily of conjugated estrogens. Isolated from mares' urine , it is manufactured by Wyeth Pharmaceuticals and has been marketed since 1942...
used in the past) are recommended during the first ten or so years of HRTHRT-Medical:* Habit reversal training* Heart rate turbulence* Hormone replacement therapy , for women* Hormone replacement therapy , for men* Hormone replacement therapy , for trans women...
to 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 estradiolEstradiolEstradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, estradiol acetate, estradiol valerate, estradiol cypionate, estradiol enanthateEstradiolEstradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, conjugated estrogens, esterified estrogens, and ethinyl estradiol. - Injectable, implanted, nasal, oral, sub lingual, gel, spray, and transdermal patchTransdermal patchA transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...
formulations are available. - As dosage increases, risks increase as well. Therefore, those with relative contraindications should start at lower doses and increase dosage more gradually.
Progestogens
- Progestogens include progesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
and progestins (synthetic analogs of progesterone or 17-alpha hydroxyprogesterone17-Hydroxyprogesterone17-Hydroxyprogesterone is a C-21 steroid hormone produced during the synthesis of glucocorticoids and sex steroids.As a hormone, 17OHP also interacts with the progesterone receptor.-Production:...
). There are oral, sublingual, suppository, gel, and injectable formulations available. - Progestogens are involved in the full maturation of the breasts, particularly the mammary structuresMammary glandA mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
lobules, acini, and alveoli. - 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, and increase energy. 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.
- Progesterone in particular is essential for bone health and seems to have a role in skin elasticity, and nerveNerveA peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
tissue. Other effects that have been seen with progesterone in particular (not the synthetics) include reducing spasms and relaxing smooth muscleSmooth muscleSmooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
tone, gallbladderGallbladderIn vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated....
activity is reduced, bronchi are widened (helps respiration), an anti-inflammatory agent and reduces the immune response, normalizing blood clotting and vascular tone, zincZincZinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
and copperCopperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
levels, cell oxygen levels, and use of fat stores for energy. Progesterone also assists in thyroidThyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
function and bone building by osteoblasts. - Progestins (synthetic progestogens) are associated with an increase risk in breast cancer, which is not seen with micronised (natural) progesterone.
Anti-androgens
- SpironolactoneSpironolactoneSpironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
is the most frequently used anti-androgen in the United States because it is relatively safe and inexpensive. Cyproterone acetate is more commonly used outside of the US. - Spironolactone is a 'potassium-sparing diuretic' that is also used to treat low-renin hypertension, edema, hyperaldosteronismHyperaldosteronismHyperaldosteronism, also aldosteronism, is a medical condition where too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood.-Types:...
, and low potassium levels caused by other diuretics. It can cause high potassium levels, hyperkalemiaHyperkalemiaHyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
, 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 and is an androgen receptor antagonistReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
(prevents androgens from binding to androgen receptors). - CyproteroneCyproteroneCyproterone acetate is an antiandrogen...
acetate is derived from 17-alpha hydroxyprogesterone17-Hydroxyprogesterone17-Hydroxyprogesterone is a C-21 steroid hormone produced during the synthesis of glucocorticoids and sex steroids.As a hormone, 17OHP also interacts with the progesterone receptor.-Production:...
and suppresses luteinizing hormoneLuteinizing hormoneLuteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(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. - Other anti-androgens include bicalutamideBicalutamideBicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer and hirsutism...
, flutamideFlutamideFlutamide is an oral nonsteroidal antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer...
, and nilutamideNilutamideNilutamide is an antiandrogen medication used in the treatment of advanced stage prostate cancer. Nilutamide blocks the androgen receptor, preventing its interaction with testosterone. Because most prostate cancer cells rely on the stimulation of the androgen receptor for growth and survival,...
. 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 ketoconazoleKetoconazoleKetoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
and cimetidineCimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
. Ketoconazole has been used in those with prostatic cancer and hirsutismHirsutismHirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
. 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 alopeciaAndrogenetic alopeciaAndrogenic alopecia is the most common cause of hair loss and thinning in humans. Variants appear in both men and women. Androgenic alopecia also occurs in chimpanzees, and orangutans. In humans, this condition is also commonly known as male pattern baldness...
) and/or an enlarged prostate (benign prostatic hyperplasiaBenign prostatic hyperplasiaBenign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....
). DHT contributes to the manifestation and exacerbation of both. Two medications are currently available to prevent the creation of DHT, finasterideFinasterideFinasteride is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...
and dutasterideDutasterideDutasteride is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone ....
. DHT levels can be lowered up to approximately 60-75% with the former depending upon dosage and up to 93-94% with the latter.
GnRH agonists
- In both sexes, the hypothalamus releases GnRH (gonadotropin-releasing hormoneGonadotropin-releasing hormoneGonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
) to stimulate the pituitary to produce LH (luteinizing hormoneLuteinizing hormoneLuteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
) and FSH (follicle-stimulating hormoneFollicle-stimulating hormoneFollicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
) which in turn cause the gonads to produce sex steroidSteroidA steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s. In adolescents of either sex with relevant indicators, GnRH agonists, such as goserelin acetateGoserelinGoserelin acetate is an injectable gonadotropin releasing hormone superagonist , also known as a luteinizing hormone releasing hormone agonist. Structurally, it is a decapeptide...
can be used to suspend the advance of sex steroid-induced, inappropriate pubertal changes for a period without inducing any changes towards the sex with which the patient currently identifies. 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 World Professional Association for Transgender Health Standards of CareStandards of care for gender identity disordersThe Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People are non-binding protocols outlining the usual treatment for individuals who wish to undergo hormonal or surgical transition to the other sex...
permit from Tanner stageTanner stageThe Tanner scale is a scale of physical development in children, adolescents and adults. The scale defines physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair, and was first...
2, but do not allow the addition of 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.
Cardiovascular
- 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 embolismPulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(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.
- 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). A study of prostate cancer patients also showed an increased number of deaths unrelated to cancer among patients taking 150 mg/day bicalutamide. This prompted Health Canada to withdraw its approval for 150 mg bicalutamide as monotherapy. 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 insufficiencyAdrenal insufficiencyAdrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
and hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
due to the action of DHT during episodes of bicalutamide withdrawalWithdrawalWithdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
. Because bicalutamide is extremely lipophilic, it is difficult to avoid periods of low serum concentration due to the uptake of bicalutamide into fat cells.
Hair
- 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 electrolysisElectrologyElectrology is the practice of electrical epilation to permanently remove human hair. The actual process of removing the hair is referred to as electrolysis.-Overview:...
/laser hair removalLaser hair removalLaser hair removal was performed experimentally for about 20 years before it became commercially available in the mid 1990s. One of the first published articles describing laser hair removal was authored by the group at Massachusetts General Hospital in 1998...
than 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. - Body hair (chest, periareolar, shoulders, back, abdomen, rear, thighs, tops of hands, tops of feet) will, over time, turn from terminalTerminal hairTerminal hairs are thick, long, and dark, as compared with vellus hair. During puberty, the increase in androgenic hormone levels causes vellus hair to be replaced with terminal hair in certain parts of the human body...
("normal") hairs to vellusVellusVellus hair, colloquially called 'peach fuzz' or 'bum fluff', is short, fine, light-colored, and barely noticeable hair that develops on most of a person's body from his/her childhood. Exceptions include the lips, the back of the ear, the palm of the hand, the sole of the foot, some external...
hairs (very tiny, blonde "baby" hairs). Hair on the arms, perianal, and perinealPerinealPerineal can refer to:* The perineum* Perineal artery* Perineal nerve...
will reduce but may not turn to vellus hair on the latter two regions (some cis 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.
Urogynecological effects
- Transgender women report a sometimes significant reduction in libidoLibidoLibido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
all 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 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 orchiectomy still 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 spermSpermThe term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
and testosteroneTestosteroneTestosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
. When testosterone is dramatically reduced spermatogenesisSpermatogenesisSpermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
is halted almost completely, when the cells that are involved in these processes go unused they atrophy (shrink). - The prostateProstateThe prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
shrinks - The bladderBladderBladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
shrinks - The line that runs down the underside of the penisPenisThe penis is a biological feature of male animals including both vertebrates and invertebrates...
and down the middle of the scrotum, the peno-scrotal raphePerineal rapheThe perineal raphe is a visible line or ridge of tissue on the human body that extends from the anus through the perineum.In men, this raphe continues through the midline of the scrotum and upwards through the posterior midline aspect of the penis...
(where the urogenital folds fused early in the womb), will darken. - Minor water retentionWater retentionWater retention can refer to:*Water retention , an abnormal accumulation of fluid in the circulatory system or within the tissues or cavities of the body...
is likely
Childbearing
- Childbearing, as experienced by women, is impossible with today's technology. Pre-operative sperm bankSperm bankA sperm bank, semen bank or cryobank is a facility that collects and stores human sperm mainly from sperm donors, primarily for the purpose of achieving pregnancies through third party reproduction, notably by artificial insemination...
ing can be done, however, allowing artificial inseminationArtificial inseminationArtificial insemination, or AI, is the process by which sperm is placed into the reproductive tract of a female for the purpose of impregnating the female by using means other than sexual intercourse or natural insemination...
to 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 uterusUterusThe uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
long enough to carry a child to term as anti-rejection drugsImmunosuppressive drugImmunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
do not seem to affect the fetus. The DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
in a donated ovumOvumAn ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
can be removed and replaced with the DNA of the receiver. Further in the future stem cell biotechnologyStem cellThis article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
may also make this possible, with no need for anti-rejection drugs.
Bone
- Both estrogenEstrogenEstrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s and androgens are necessary in both biological males and females for healthy boneBoneBones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
. (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.
Drug interactions
- 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.
Skin
- The uppermost layer of skin, the stratum corneumStratum corneumThe stratum corneum is the outermost layer of the epidermis, consisting of dead cells that lack nuclei and organelles. The purpose of the stratum corneum is to form a barrier to protect underlying tissue from infection, dehydration, chemicals and mechanical stress...
, 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 glandSebaceous glandThe sebaceous glands are microscopic glands in the skin that secrete an oily/waxy matter, called sebum, to lubricate and waterproof the skin and hair of mammals...
activity (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."
- Many 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).
- More subcutaneous (under skin) adipose (fat) tissue accumulates. This gives a more puffy/softer appearance. Consequently dimpling, or celluliteCelluliteCellulite is a topographic skin change that occurs in most postpubertal females. It presents as a modification of skin topography evident by skin dimpling and nodularity that occurs mainly in women on the pelvic region, lower limbs, and abdomen, and is caused by the herniation of subcutaneous fat...
, 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 marksStretch marksStretch marks or striae , as they are called in dermatology, are a form of scarring on the skin with an off-color hue. They are caused by tearing of the dermis, and over time can diminish but not disappear completely....
(striae distensae) may appear on the skin in these areas.
Ocular changes
- The lens of the eyes changes in curvature.
- Due to decreased androgens, the meibomian glandMeibomian glandThe meibomian glands are a special kind of sebaceous gland at the rim of the eyelids inside the tarsal plate, responsible for the supply of meibum, an oily substance that prevents evaporation of the eye's tear film. They prevent tear spillage onto the cheek, trapping tears between the oiled edge...
s (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.
Senses
- Sensitivity to male body odor(s) (including male pheromones) may be positively correlated with elevated estrogen levels. Overall, olfactory senses may increase. Progestogens, however, often lower the sensitivity to male pheromones.
Mammary gland development
- BreastBreastThe breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
, nippleNippleIn its most general form, a nipple is a structure from which a fluid emanates. More specifically, it is the projection on the breasts or udder of a mammal by which breast milk is delivered to a mother's young. In this sense, it is often called a teat, especially when referring to non-humans, and...
, and areolar development takes 4–6 years to complete depending upon geneticsGeneticsGenetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, and sometimes as long as 10 years. It is normal for there to be a "stall" in breast growth during feminizationFeminizationFeminization can refer to:*Feminization the hormonally induced development of female sexual characteristics*Feminization a sexual or lifestyle practice where a person assumes a female role...
, or for the size of one breast to be a little bigger than the other. MtF who undergo HRTHRT-Medical:* Habit reversal training* Heart rate turbulence* Hormone replacement therapy , for women* Hormone replacement therapy , for men* Hormone replacement therapy , for trans women...
often experience breast development which is below the comparable cis femaleFemaleFemale is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
norm (many seek breast augmentationBreast augmentationBreast augmentation denotes the breast implant and fat-graft mammoplasty procedures for correcting the defects, and for enhancing the size, form, and feel of a woman’s breasts...
); it is rare for a HRT patient to opt for breast reductionBreast reductionReduction mammoplasty is the plastic surgery procedure for correcting over-sized breasts...
. 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 in cis females, i.e., if a cis 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 transwoman opts to have breast augmentation, the implants used are, on the average, larger than those commonly used by cis females. - The nipples will become more sensitive to stimulationStimulationStimulation is the action of various agents on nerves, muscles, or a sensory end organ, by which activity is evoked; especially, the nervous impulse produced by various agents on nerves, or a sensory end organ, by which the part connected with the nerve is thrown into a state of activity.The word...
.
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.
Gastrointestinal
- 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.
Neurological/Psychiatric
- Mood changes can occur - including the development of depression, particularly in those who take progestinProgestinA progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
s. Medroxyprogesterone acetateMedroxyprogesteroneMedroxyprogesterone is a pregnane that acts as a progestin. An acylated derivative, medroxyprogesterone 17-acetate is clinically used as a drug. Compared to MPA, MP is approximately 100 fold less potent as a progestin...
, in particular, has been shown to cause depression in certain individuals, perhaps due to its possible effect on dopamine levels. - Migraines can be made worse or unmasked by estrogen therapy
- Estrogens can induce the development of prolactinomaProlactinomaA prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
s, 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 hypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
. - Some people have noticed a feeling of self-contentment after starting HRT.
- Recent studies have indicated that cross-hormone therapy in transwomen may result in a reduction in brain volume towards female proportions.
Metabolic
- 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.
External links
- Tom Waddell Clinic Transgender Protocol - MTF and FTM clinical protocols aimed at providers