Female Sex Hormones, their Types, And Their Effects. Let’s get started by talking about the main medications of female sex hormone replacement therapy.
Types of Female sex Hormone Replacement Therapy
Estrogens are the major female sex hormone in women and are responsible for the development and maintenance of feminine secondary sexual characteristics,
Estrogens act by binding to and activating the estrogen receptor on cells in the body.
The estrogens that are used in transgender women are estradiol and estradiol esters such as estradiol valerate and estradiol cypionate.
Other, non-bioidentical estrogens such as Ethinylestradiol and conjugated estrogens are resistant to metabolism in the liver and have a higher impact on the liver resulting in a greater risk of blood clots, cardiovascular issues, insulin resistance, and other health problems.
For this reason, as well as the fact that high doses of estrogens are needed to suppress testosterone levels in transgender women who still possess gonads, these estrogens should ideally never be used as the estrogen component in male-to-female hormone replacement therapy.
Estrogen can be used alone at high doses to suppress testosterone levels in the female or castrate range. Higher doses of estrogens may have a greater risk of adverse health effects such as blood clots and cardiovascular issues, so the use of a lower and more physiological dose of estrogen may be optimal.
Alternatively, estrogen can be used at lower doses that result in more physiological estrogen levels in combination with appropriate doses of an antiandrogen, a secondary antigonadotropin, or a GnRH agonist or antagonist.
More on these later. Higher doses of estrogens may have a greater risk of adverse health effects such as blood clots and cardiovascular issues, so the use of lower and more physiological doses of estrogens may be optimal.
However, it should also be noted that overall risks of health complications with high-dose estradiol are low and much smaller than those of non-bioidentical estrogens like conjugated estrogens and ethinylestradiol.
Health complications are likely a (Female Sex Hormone) concern mainly to people with specific risk factors, including those who are of older age, who smoke, and who are obese, among others. In addition to potential health risks, however, there is some indication that high doses of estrogens may compromise breast development.
Effects in Body
And a feminine pattern of fat distribution.
There are other types of female sex hormones, known as progestogens. Unlike estrogens, progestogens are not known to be involved in the development of female secondary sexual characteristics and hence are not believed to contribute to the feminization of women.
Progestogens can suppress testosterone levels however and are sometimes used as an antiandrogen. Progestogens include progesterone and progestins, such as medroxyprogesterone acetate, Norethisterone, and hydroxyprogesterone caproate.
Progestins are synthetic progestogens, while progesterone is biologically identical to what is found naturally in the body.
Progesterone is mainly involved in the regulation of the female reproductive system,
The menstrual cycle,
Pregnancy, And Lactation.
Progestins are sometimes used at high (Female Sex Hormone) doses due to their ability to suppress testosterone. In general, it appears that bioidentical progesterone may be safer long-term than progestins in regards to health, and so progesterone may be the preferred progestogen for use in male-to-female HRT.
However, there is also an indication that progesterone may actually not fundamentally differ from progestins in terms of health. In addition to estrogens and progestogens,
There is another class of hormonal medications used in male-to-female HRT known as anti-androgens.
Anti-Androgens And Androgens
The addition of anti-androgens to estrogen therapy can suppress or block the remaining testosterone that isn’t suppressed by estrogen therapy alone.
These medications cancel the effects of androgens in the body. They work by a variety of different mechanisms of action. Androgen receptor antagonists work by directly blocking the effects of androgens and Antigonadotropins work by suppressing the gonadal production of androgens and preventing the creation of androgens.
Antiandrogens which are androgen receptor antagonists include steroidal anti-androgens like spironolactone and cyproterone acetate as well as nonsteroidal anti-androgens like bicalutamide.
Spironolactone and bicalutamide work by directly blocking the effects of androgens, however, they do not suppress testosterone levels, and their antiandrogenic ability is limited by this fact; relatively high doses are required for adequate prevention of the effects of testosterone, especially in the context of high testosterone levels.
However, pure AR antagonists like spironolactone and bicalutamide can be very useful when testosterone levels are incomplete but largely suppressed.
Because pure AR antagonists do not work by lowering testosterone levels, blood work is less useful for them. Spironolactone has anti mineralocorticoid side effects and has a rare risk of potentially life-threatening hyperkalemia in those with specific risk factors.
Monitoring of blood potassium levels during spironolactone therapy is advisable in those with risk factors for hyperkalemia but appears to not be necessary for people without such risk factors.
Risk factors for hyperkalemia include old age, chronic kidney disease, using potassium supplements, and using ACE inhibitors. Spironolactone has also been found to decrease the estradiol levels achieved by oral estradiol.
Bicalutamide is a more potent, and effective androgen receptor antagonist than spironolactone and has fewer side effects, including no anti mineralocorticoid effects of hyperkalemia risk. It has almost no side effects in women.
Bicalutamide also does not negatively interact with estradiol. It has a small risk of elevated liver enzymes and very rare occurrences of liver damage and lung disease.
It is advisable to monitor liver enzymes when taking bicalutamide. Bicalutamide has mostly been used to treat men with prostate cancer, but it has also been used to treat other androgen-dependent conditions and is becoming increasingly used in transgender women.
Due to its various advantages over spironolactone, it is possible that bicalutamide may eventually replace spironolactone as an antiandrogen for transgender women.
Cyproterone acetate works by blocking the effects of androgens, and also by strongly suppressing levels of testosterone to its very potent progestogenic activity.
The suppression of testosterone levels (Female Sex Hormone) by cyproterone acetate greatly improves its effectiveness as an antiandrogen; relatively low doses of cyproterone acetate may be able to maximally suppress the testosterone levels when in combination with low to moderate doses of estrogen.
Cyproterone acetate may have some risk of depression. It also has a risk of elevated liver enzymes and rare occurrences of liver damage, blood clots, and non-cancerous brain tumors.
Monitoring of liver enzymes and prolactin levels allows for the detection of liver problems and one of the types of brain tumor and is advisable during Cyproterone acetate therapy.
The side effects and risks of Cyproterone acetate may be reduced by using the lowest effective dosage, which may be far lower than what is often used clinically.
Cyproterone acetate is notably not approved for use in the United States, but it is available in most other countries.
Although estrogens and progestogens are antigonadotropins and therefore functionally antiandrogenic, they are not usually referred to as & Antiandrogens instead, the term is most commonly reserved to describe other antiandrogens, especially androgen receptor antagonists like spironolactone,
Cyproterone acetate, and bicalutamide. Some medications are classified as Antigonadotrophins, including certain high-dose estrogen and progestogen therapies.
Antigonadotrophins also include GnRH agonists and antagonists. GnRH agonists and antagonists work by completely blocking the effects of GnRH, which stops gonadal sex hormone production.
They are like reversible orchiectomy and are the ideal antiandrogens for use in transgender women. GnRH agonists and antagonists have essentially no side effects or risks if taken together with estrogen to prevent the withdrawal effects of sex hormone deficiency.
However, they, unfortunately, tend to be too expensive or unavailable. An exception may be buserelin, which has recently become available online at a very low cost in America.
Other medications known as androgen synthesis inhibitors are occasionally used in male-to-female hormone replacement therapy, although they are generally not likely to be beneficial.
Androgen Synthesis Inhibitors
Androgen synthesis inhibitors include 5α-reductase inhibitors like finasteride and dutasteride. Androgen synthesis inhibitors do not prevent the production or effect of testosterone, but instead prevent the conversion of testosterone into more potent forms such as dihydrotestosterone in certain tissues such as the skin, hair follicles, and prostate gland.
Because of this, their antiandrogenic effectiveness is limited to the treatment of scalp hair loss, excessive facial and body hair growth, and prostate disorders.5α-reductase inhibitors are inappropriate general antiandrogens in transgender women as they have little or no influence on the effects of testosterone elsewhere in the body.
They may also have a small risk of depression. If a 5α-reductase inhibitor is used, dutasteride is more effective than finasteride and is preferred. Sometimes androgens and anabolic steroids such as testosterone are added to male-to-female sex hormone replacement therapy.
This is done when androgen levels are low and androgen replacement is desired. Possible options for androgen therapy include testosterone, DHEA, and nandrolone decanoate.
It has been proposed that increasing levels of testosterone may provide benefits such as increased sexual desire, improved mood and energy, positive effects on skin health and cellulite, and increased muscle size and strength.
However, it should be noted that testosterone has only been shown to have slight effects on sexual desire in women even at well above-normal levels, and there is insufficient evidence to support mental benefits in women such as improved mood or energy at present.