**Know-How of the Hormonal Therapy and the Effect of the Male Hormone on Uterus in the Female to Male Transsexuals**

Seok Kwun Kim1 and Myoungseok Han2 *1Department of Plastic and Reconstructive Surgery, 2Department of Obstetrics and Gynecology, Dong-A University School of Medicine, South Korea* 

## **1. Introduction**

334 Hysterectomy

To MS, Fonseca EB, Molina FS, et al: Maternal characteristics and cervical length in the

To MS, Skentou C, Liao AW, Cacho A, Nicolaides KH. Cervical length and funneling at 23

Topping J, Farquharson RG. Transabdominal cervical cerclage. Br J Hosp Med. 1995;54:510-

Turnquest MA, Britton KA, Brown HL. Outcome of patients undergoing trasabdominal

Weiner CP, Lee KY, Buhimschi CS, Christner R, Buhimschi IA. 2005. Proteomic biomarkers

Word RA, Li XH, Hnat M, et al: Dynamics of cervical remodelling during pregnancy and parturition: mechanisms and current concepts. Sem Reprod Med 25:69-79,2007 Yellon SM, Ebner CA, Elovitz MA: Medroxyprogesterone acetate modulates remodelling,

Zeisler H, Journa EA, Bancher –Todesca D, et al. Prophylactic cerclage in pregnancy. Effect on women with a history of conization. J Reprod Med 1997;42:390-392

cerclage: a descriptive study. J Matern Fetal Med. 1999;9:225-227

inflammation-induced preterm birth. Reprod Sci 16:257-264,2009

41

12

194:1360-65,2006

Ultrasound Obstet Gynecol 2001;18:200-203

and Gynecology.192:710-718

premature rupture of the membranes. Eur J Obstet Gynecol Repord Biol 47 (1992)

prediction of spontaneous early preterm delivery in twins. Am J Obstet Gynecol

weeks of gestation in the prediction of spontaneous early preterm delivery.

that predict the clinical success of rescue cerclage. American Journal of Obstetrics

immune cell census, and nerve fibers in the cervix of a mouse model for

Management of the patient with gender identity disorder involves many different aspects of medical care. Transsexualism is a multidimensional phenomenon that requires a multidisciplinary approach in both the diagnostic and treatment phases. Endocrinologists have to work together with mental health professionals and surgeons to provide full counselling, confirm the diagnosis and avoid mistakes or regrets. Hormonal therapy not only has a therapeutic role but also an important diagnostic tool.

Trends in Europe are toward treatment of patients at early age if the diagnosis is appropriately established. This may begin with blocking agents that temporarily suppress pubertal transformation. Secondary sexual trait suppression allows much more successful gender transformation.

Hormonal therapy is used to suppress secondary sexual characteristic of the biological sex, to induce the secondary sex characteristics of the new sex. This therapy should continue lifelong[1].

## **2. Masculinizing effect in female to male hormonal therapy**

Endocrinologic masculinization is achieved by the use of testosterone to induce male physical characteristics. Testosterone works primarily by direct stimulation of receptors in target tissues. It elevates serum testosterone level to a male reference range rather than a decrease in serum estradiol[2]. Testosterone also has antigonadotropic action in high doses.

Rapidity and degree of change from testosterone therapy depends on the agents used, dosage, and the patient's responsiveness to endocrine therapy. Typically, within the first 1-3 months patients experience oilier skin and acne, increased libido, increased muscle mass and upper body strength, and redistribution of the fat to a more masculine pattern[3, 12].

Know-How of the Hormonal Therapy and the Effect

**3. Recommended masculinizing male hormone regimen** 

Serum testosterone level should be maintained <55 ng/dl.

Androderm® patch is also applied 5 – 10 g daily [23].

of comprehensive care of all health concerns.

adjustment, and every 6 - 12 months thereafter.

[23].

therapy.

of the Male Hormone on Uterus in the Female to Male Transsexuals 337

Most commonly used preparations are injectable testoterone esters (Jenatestoterone®) administration intramuscularly in dose 200 - 250 mg every two weeks [21]. Sometimes, masculinization effect is low or when patient wants to bring rapid masculinization testosterone esters administrated intramuscularly in dose 200 - 250 mg every week. Serum testosterone level is checked every 3 months for first year and then 1 - 2 times per year afterward for appropriate signs of feminization and for development of adverse reaction.

At least 12 months of treatment of testosterone can achieve the masculinization. After oophorectomy or achievement of masculinization, administration of testosterone will be reduced to every three or four weeks. Serum testosterone level should be needed to keep within the middle or lower-middle end of the male range. Long acting testosterone undecanoate 1000 mg is available and injections may leave a space at 10 - 12 weeks [22], but masculinizing effect is not certain. Transdermal gel and transdermal patch can be used and also provide good, steady-state testosterone level. AndroGel® is applied 5 - 10 g qd.

To preserve bone density following oophorectomy, testosterone supplementation should be maintained throughout life, and calcium and vitamine D supplementation is recommended

At minimum, patients should be seen every month after initiating treatment or while adjusting medication dosages, then every 3 months for the first year, then every six months thereafter. The primary focus of monitoring cross-sex hormone use is to assess the degree of masculinization and the possible presence of adverse effects of medication. However, as with monitoring of any long-term medication, monitoring should take place in the context

Mascullinization takes place gradually over a period of years. Observed changes to male pattern hair growth and voice should be noted, and the patient should be asked about changes to menstrual pattern, mood, clitoral growth, libido, and sexual function. Other changes should also be noted. To avoid a supraphysiological dose of testosterone, serum free testosterone should be checked 2 - 4 weeks after the starting dose or after a dose

All exams should include assessment of weight, cardiovascular risk, diabetes risk, and blood pressure. There are case reports of destabilization of bipolar disorder, schizophrenia, and schizoaffective disorder in non-transgender men with the use of testosterone. Mental health should be monitored carefully in FTMs with these condition for the duration of testosterone

At minimum, laboratory tests should include fasting blood glucose, hemoglobin, lipid profile, and liver enzymes. The fasting blood glucose should be checked 3 and 6 months after starting testosterone or after a dose adjustment, then annually increase frequency and

**4. Recommended monitoring following initial testosterone therapy** 

The voice changes to crack and deepen within the first 3-6 months, but it can take a year or more for the voice pitch to fully drop [13].

In 75% FTMs testosterone will cause voice pitch to drop to a level sufficient for passability as male even on the telephone [4].

The clitoral enlargement begins within the first few months of testosterone initiation and typically plateaus within the first year [14, 15]. The degree of enlargement is variable with studies reporting a range of 3.5 – 6 cm maximal when stretched [14, 15, 16]. Clitoral growth dose not appear to be enhanced by topical application of testosterone to the clitoris.

Long-term testosterone use causes vaginal and cervical atrophy [3, 17], with decreased vaginal secretion and difficult penetration [12].

In most cases, menses stop within 1 – 6 months [5-8, 14-16, 18, 19]. If after three months menses have not stopped, the dosage of testosterone may be increased until serum free testosterone is within upper quartile of the normal male range or menses stop. Despite endometrial atrophy, cessation of menses, and reduced fertility there is evidence of ovulation even after several years of testosterone administration [17].

There is gradual increased growth, coarseness, and thickness of hair on the torso and extremities in the first year [3, 4, 6, 7, 16]. Facial hair increases more slowly, typically taking 1 - 4 years to reach full growth. Some patients experience male pattern baldness during this later stage of masculinization [4, 6-8, 11, 20].

Voice change, facial hair growth and male pattern baldness are not reversible, which other changes are reversible if hormone is stopped. Clitoral growth and sterility may or may not reversible(Table 1).


Table 1. Masculinizing effects in FTM transsexual persons

The voice changes to crack and deepen within the first 3-6 months, but it can take a year or

In 75% FTMs testosterone will cause voice pitch to drop to a level sufficient for passability as

The clitoral enlargement begins within the first few months of testosterone initiation and typically plateaus within the first year [14, 15]. The degree of enlargement is variable with studies reporting a range of 3.5 – 6 cm maximal when stretched [14, 15, 16]. Clitoral growth

Long-term testosterone use causes vaginal and cervical atrophy [3, 17], with decreased

In most cases, menses stop within 1 – 6 months [5-8, 14-16, 18, 19]. If after three months menses have not stopped, the dosage of testosterone may be increased until serum free testosterone is within upper quartile of the normal male range or menses stop. Despite endometrial atrophy, cessation of menses, and reduced fertility there is evidence of

There is gradual increased growth, coarseness, and thickness of hair on the torso and extremities in the first year [3, 4, 6, 7, 16]. Facial hair increases more slowly, typically taking 1 - 4 years to reach full growth. Some patients experience male pattern baldness during this

Voice change, facial hair growth and male pattern baldness are not reversible, which other changes are reversible if hormone is stopped. Clitoral growth and sterility may or may not

**Effect Onset**

Skin oiliness/acne 1-6 1-2

Facial/body hair growth 6-12 4-5

Increased muscle mass/strength 6-12 2-5

Fat redistribution 1-6 2-5

Clitoral enlargement 3-6 1-2

Vaginal atrophy 3-6 1-2

Deepening of voice 6-12 1-2

Scalp hair loss 6-12

Cessation of menses 2-6

Table 1. Masculinizing effects in FTM transsexual persons

**(months)**

**Maximum (yr)**

dose not appear to be enhanced by topical application of testosterone to the clitoris.

ovulation even after several years of testosterone administration [17].

more for the voice pitch to fully drop [13].

vaginal secretion and difficult penetration [12].

later stage of masculinization [4, 6-8, 11, 20].

reversible(Table 1).

male even on the telephone [4].

## **3. Recommended masculinizing male hormone regimen**

Most commonly used preparations are injectable testoterone esters (Jenatestoterone®) administration intramuscularly in dose 200 - 250 mg every two weeks [21]. Sometimes, masculinization effect is low or when patient wants to bring rapid masculinization testosterone esters administrated intramuscularly in dose 200 - 250 mg every week. Serum testosterone level is checked every 3 months for first year and then 1 - 2 times per year afterward for appropriate signs of feminization and for development of adverse reaction. Serum testosterone level should be maintained <55 ng/dl.

At least 12 months of treatment of testosterone can achieve the masculinization. After oophorectomy or achievement of masculinization, administration of testosterone will be reduced to every three or four weeks. Serum testosterone level should be needed to keep within the middle or lower-middle end of the male range. Long acting testosterone undecanoate 1000 mg is available and injections may leave a space at 10 - 12 weeks [22], but masculinizing effect is not certain. Transdermal gel and transdermal patch can be used and also provide good, steady-state testosterone level. AndroGel® is applied 5 - 10 g qd. Androderm® patch is also applied 5 – 10 g daily [23].

To preserve bone density following oophorectomy, testosterone supplementation should be maintained throughout life, and calcium and vitamine D supplementation is recommended [23].

## **4. Recommended monitoring following initial testosterone therapy**

At minimum, patients should be seen every month after initiating treatment or while adjusting medication dosages, then every 3 months for the first year, then every six months thereafter. The primary focus of monitoring cross-sex hormone use is to assess the degree of masculinization and the possible presence of adverse effects of medication. However, as with monitoring of any long-term medication, monitoring should take place in the context of comprehensive care of all health concerns.

Mascullinization takes place gradually over a period of years. Observed changes to male pattern hair growth and voice should be noted, and the patient should be asked about changes to menstrual pattern, mood, clitoral growth, libido, and sexual function. Other changes should also be noted. To avoid a supraphysiological dose of testosterone, serum free testosterone should be checked 2 - 4 weeks after the starting dose or after a dose adjustment, and every 6 - 12 months thereafter.

All exams should include assessment of weight, cardiovascular risk, diabetes risk, and blood pressure. There are case reports of destabilization of bipolar disorder, schizophrenia, and schizoaffective disorder in non-transgender men with the use of testosterone. Mental health should be monitored carefully in FTMs with these condition for the duration of testosterone therapy.

At minimum, laboratory tests should include fasting blood glucose, hemoglobin, lipid profile, and liver enzymes. The fasting blood glucose should be checked 3 and 6 months after starting testosterone or after a dose adjustment, then annually increase frequency and

Know-How of the Hormonal Therapy and the Effect

4. Decreased serum high-density lipoprotein (HDL) cholesterol

1. Water and sodium retention

3. Decreased carbohydrate tolerance

7. Emotional or psychiatric problems

2. Increased erythropoiesis

5. Elevated liver enzymes

6. Weight increase >10%

10. Endometrial hyperplasia

11. Aggression and hypersexuality

14. Decreased bone mineral density after gonadectomy

Table 2. Side Effects of Androgen Therapy in F-T-M Transsexuals

**6. The effect of the testosterone on uterus and ovary** 

Human endometrium is a steroid-hormone-dependent tissue whose growth and remodeling respond to estrogen and progesterone secreted from ovary. Increasing circulating estradiol (E2) levels, a consequence of ovarian follicular growth named as 'follicular' phase of the cycle, promote endometrial cellular proliferation and tissue thickness, from approximately 2 mm after the postmenstrual repair phase, to 10–12 mm in the periovulatory period. [34] Although myometrial tissues are also influenced by estrogen stimulation for the growth and

Testosterone treatments to the female to male transsexuals are a usual method to induce masculinization. Testosterone is one of the potent circulating androgens which are produced from testis and ovary. Ovary and adrenal gland in women produce not only female sex hormones and mineralcorticoid, but also androgens, such as testosterone, androstenedione and dehydroepiandrostenedione or its sulfate. Several studies have shown that high plasma androgen levels are associated with adverse reproductive outcome, including infertility and increased incidence of miscarriage.[35, 36] Those clinical features imply that androgens have a potency to affect the endometrial cellular function and promote histological changes.

remodeling, they do not show such dramatic change as much as endometrium.

12. Decreased insulin sensitivity

8. Sleep apnea

13. Increased IGF

15. Ovarian cancer

9. Acne

of the Male Hormone on Uterus in the Female to Male Transsexuals 339

monitor A1c if elevated lipids, significant weight gain, elevated fasting glucose levels, personal history of glucose intolerance, or family history of diabetes. Hemoglobin should be checked 3 and 6 months after starting testosterone or after a dose adjustment, then annually. Lipid profile is needed to evaluate 3 and 6 months after starting testosterone or after a dose adjustment, then annually. Liver enzymes also should be checked 3 and 6 months after starting testosterone or after dose increase, then annually.

## **5. Effect of the long-term treatment of testosterone on health**

The goal of treatment in the FTM is to induce virilization, deepening of the voice, production of male-pattern body hair growth, and physical contours, and cessation of menses.

The principal hormonal treatment used to accomplish these goals is testosterone preparation. After reassignment surgery, which includes oophorectomy and hysterectomy, hormonal therapy must be continued. It is reasonable to assume that the principles of treatment are very similar to a person without their own gonadal hormone secretion.

An unresolved question is whether in the long term all functions of sex steroids of a subject are adequately covered by cross-sex hormones and whether the administration of cross-sex hormones is appropriate safe. Nearly all hormone related biochemical processes can be sex reversed by administration of cross-sex hormone.

The complication of cross-sex hormone therapy is underreported. Although complications occurring in the long term are seen in general practice, and these complication are only occasionally reported in the scientific literature.

Polycythemia and erythrocytosis were observed in testosterone administration as a rare complication[24, 25]. Relative contraindication (e.g. persons who smoke, have diabetes, have liver diseases,etc) to therapy have been published and should have an in-depth discussion with their physician to balance the risk and benefit of therapy[26]. The worrisome complication of water and sodium retention increased body weight, decreased insulin sensitivity, obstructive sleep apnea, acne, poor lipid profile, and an increase in hematocrit have raised the concern for cardiac and thromboembolytic events.

Cerebral vascular accidents have been reported for individuals with supraphysiological level of testosterone[27, 28]. Polycystic ovarian disease is a risk factor for endometrial cancer[27] As the association between polycystic ovarian disease and risk of endometrial and ovarian malignancy are not entirely clear and seen in greater numbers in transsexual people before androgen therapy than in the general population[28, 29]. Mild endometrial hyperplasia has been appreciated on removal of the uterus[30]. A case reported in 2 transsexuals with ovarian cancer[31]. Recommendation for hysterectomy and bilatel salpingoooporectomy, generally carried out around 15 months after the start of testosterore treatment in the male to female transsexuals, has yet to be fully justified, at least on the grounds of enhanced risk of malignancy.

Total hysterectomy after 2 years of testosterone therapy, followed by 50% reduction in hormone man be a way to avoid these risks[32, 33](Table 2).

1. Water and sodium retention



338 Hysterectomy

monitor A1c if elevated lipids, significant weight gain, elevated fasting glucose levels, personal history of glucose intolerance, or family history of diabetes. Hemoglobin should be checked 3 and 6 months after starting testosterone or after a dose adjustment, then annually. Lipid profile is needed to evaluate 3 and 6 months after starting testosterone or after a dose adjustment, then annually. Liver enzymes also should be checked 3 and 6 months after

The goal of treatment in the FTM is to induce virilization, deepening of the voice, production of male-pattern body hair growth, and physical contours, and cessation of

The principal hormonal treatment used to accomplish these goals is testosterone preparation. After reassignment surgery, which includes oophorectomy and hysterectomy, hormonal therapy must be continued. It is reasonable to assume that the principles of

An unresolved question is whether in the long term all functions of sex steroids of a subject are adequately covered by cross-sex hormones and whether the administration of cross-sex hormones is appropriate safe. Nearly all hormone related biochemical processes can be sex

The complication of cross-sex hormone therapy is underreported. Although complications occurring in the long term are seen in general practice, and these complication are only

Polycythemia and erythrocytosis were observed in testosterone administration as a rare complication[24, 25]. Relative contraindication (e.g. persons who smoke, have diabetes, have liver diseases,etc) to therapy have been published and should have an in-depth discussion with their physician to balance the risk and benefit of therapy[26]. The worrisome complication of water and sodium retention increased body weight, decreased insulin sensitivity, obstructive sleep apnea, acne, poor lipid profile, and an increase in hematocrit

Cerebral vascular accidents have been reported for individuals with supraphysiological level of testosterone[27, 28]. Polycystic ovarian disease is a risk factor for endometrial cancer[27] As the association between polycystic ovarian disease and risk of endometrial and ovarian malignancy are not entirely clear and seen in greater numbers in transsexual people before androgen therapy than in the general population[28, 29]. Mild endometrial hyperplasia has been appreciated on removal of the uterus[30]. A case reported in 2 transsexuals with ovarian cancer[31]. Recommendation for hysterectomy and bilatel salpingoooporectomy, generally carried out around 15 months after the start of testosterore treatment in the male to female transsexuals, has yet to be fully justified, at least on the

Total hysterectomy after 2 years of testosterone therapy, followed by 50% reduction in

treatment are very similar to a person without their own gonadal hormone secretion.

starting testosterone or after dose increase, then annually.

reversed by administration of cross-sex hormone.

occasionally reported in the scientific literature.

grounds of enhanced risk of malignancy.

have raised the concern for cardiac and thromboembolytic events.

hormone man be a way to avoid these risks[32, 33](Table 2).

menses.

**5. Effect of the long-term treatment of testosterone on health** 

Table 2. Side Effects of Androgen Therapy in F-T-M Transsexuals

## **6. The effect of the testosterone on uterus and ovary**

Human endometrium is a steroid-hormone-dependent tissue whose growth and remodeling respond to estrogen and progesterone secreted from ovary. Increasing circulating estradiol (E2) levels, a consequence of ovarian follicular growth named as 'follicular' phase of the cycle, promote endometrial cellular proliferation and tissue thickness, from approximately 2 mm after the postmenstrual repair phase, to 10–12 mm in the periovulatory period. [34] Although myometrial tissues are also influenced by estrogen stimulation for the growth and remodeling, they do not show such dramatic change as much as endometrium.

Testosterone treatments to the female to male transsexuals are a usual method to induce masculinization. Testosterone is one of the potent circulating androgens which are produced from testis and ovary. Ovary and adrenal gland in women produce not only female sex hormones and mineralcorticoid, but also androgens, such as testosterone, androstenedione and dehydroepiandrostenedione or its sulfate. Several studies have shown that high plasma androgen levels are associated with adverse reproductive outcome, including infertility and increased incidence of miscarriage.[35, 36] Those clinical features imply that androgens have a potency to affect the endometrial cellular function and promote histological changes.

Know-How of the Hormonal Therapy and the Effect

of the Male Hormone on Uterus in the Female to Male Transsexuals 341

Fig. 2. Atrophy of endometrium (H-E, ×200). (Kor J Fertil Steril 2005;32:325-330)

Fig. 3. Multiple cystic follicles in the ovarian cortex (H-E, X10) (Kor J Fertil Steril 2005;32:325-

330)

Polycystic ovary syndrome (PCOS), which is characterized by high circulating testosterone and androstenedione level, expresses different endometrial pattern, such as endometrial hyperplasia or cancer, compared to women with normal androgen level.[37] Those pathologic changes in PCOS patients are attributed to estrogen stimulation to the endometrium, which is aromatized from circulating androgens. Hyperandrogenic symptoms like acne or hirsutism are found in some PCOS patients.

However, it is rarely reported what effect on the uterus would be observed after long term exogenous testosterone treatment among FTM patients. Although it is easily acceptable that there are no definite gross changes of uterus and ovary, interesting histological features are expressed in a few articles. In 1986, Miller et al. reported histologic characteristics of uterus extirpated from FTMs. In the study, severe atrophied uterine cervix was found and variable degrees of atrophic change of endometrium were observed as well.[38] Such changes have been also observed in our previous histologic study on the extirpated uterus from 16 FTMs.(Fig.1, Fig.2) These changes are comparable with proliferative change of endometrium in PCOS. This means that androgen action on endometrium in FTMs is much higher than that of PCOS patients. Meanwhile, we also found that ovarian histologic changes in FTMs were polycystic appearance similar to those of PCOS.[39](Fig. 3) It is thought that the polycystic change of ovary might be due to multiple follicle recruitment action caused by androgen, which is thought to be the pathophysiologic theory about PCOS.

Finally, it is concluded that the histolgic changes of endometrium and ovary are atrophic and polycystic appearance according to the duration of testosterone treatments. Molecular mechanisms on those changes would be clarified in the future.

Fig. 1. Atrophied epithelium of exocervix (H-E, X400) (Kor J Fertil Steril 2005;32:325-330)

Polycystic ovary syndrome (PCOS), which is characterized by high circulating testosterone and androstenedione level, expresses different endometrial pattern, such as endometrial hyperplasia or cancer, compared to women with normal androgen level.[37] Those pathologic changes in PCOS patients are attributed to estrogen stimulation to the endometrium, which is aromatized from circulating androgens. Hyperandrogenic

However, it is rarely reported what effect on the uterus would be observed after long term exogenous testosterone treatment among FTM patients. Although it is easily acceptable that there are no definite gross changes of uterus and ovary, interesting histological features are expressed in a few articles. In 1986, Miller et al. reported histologic characteristics of uterus extirpated from FTMs. In the study, severe atrophied uterine cervix was found and variable degrees of atrophic change of endometrium were observed as well.[38] Such changes have been also observed in our previous histologic study on the extirpated uterus from 16 FTMs.(Fig.1, Fig.2) These changes are comparable with proliferative change of endometrium in PCOS. This means that androgen action on endometrium in FTMs is much higher than that of PCOS patients. Meanwhile, we also found that ovarian histologic changes in FTMs were polycystic appearance similar to those of PCOS.[39](Fig. 3) It is thought that the polycystic change of ovary might be due to multiple follicle recruitment action caused by

Finally, it is concluded that the histolgic changes of endometrium and ovary are atrophic and polycystic appearance according to the duration of testosterone treatments. Molecular

Fig. 1. Atrophied epithelium of exocervix (H-E, X400) (Kor J Fertil Steril 2005;32:325-330)

symptoms like acne or hirsutism are found in some PCOS patients.

androgen, which is thought to be the pathophysiologic theory about PCOS.

mechanisms on those changes would be clarified in the future.

Fig. 2. Atrophy of endometrium (H-E, ×200). (Kor J Fertil Steril 2005;32:325-330)

Fig. 3. Multiple cystic follicles in the ovarian cortex (H-E, X10) (Kor J Fertil Steril 2005;32:325- 330)

Know-How of the Hormonal Therapy and the Effect

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of the Male Hormone on Uterus in the Female to Male Transsexuals 343

[11] Dimensions (2003). Informed consent for testostorone therapy for female-to-male

[12] The Gender Centre Inc. (2001). Testosterone hormone information II. Sydney, Australia:

[13] Van Borsel, J., De Cuypere, G., Rubens, R., & Destaerke, B. (2000). Voice problems in

[14] Gooren, L. J. G. (n.d.). Transsexualism: Introduction and general aspects of treatment.

[15] Meyer, W. J., III, Webb, A., Stuart, C. A., Finkelstein, J. W., Lawrence, B., & Walker, P.

[16] Meyer, W. J., III, Finkelstein, J. W., Stuart, C. A., Webb, A., Smith, E. R., Payer, A. F., &

[17] Miller, N., Bedard, Y. C., Cooter, N. B., & Shaul, D. L. (1986). Histological changes in the

[18] Futterweit, W. (1998). Endocrine therapy of transsexualism and potential complications

[19] Israel, G. E, & Tarver, D. E. I. (1997). Transgender care: Recommended guidelines,

[20] Feldman, J. & Bockting, W. O. (2003). Transgender health. Minnesota Medicine, 86, 25-

[21] Louis, J. G., Erik J. G., & Mathijs, C. B. (2008). Long-Term Treatment of Transsexuals

[22] Louis, G. (2005). Hormone Treatment of the Adult Transsexual Patient. Horm Res, 64(2),

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[25] Ammus, S. (1989) The role of androgens in the treatment of hematologic disorders. Adv

[26] Nagelberg, S., Laue, L., Loriaux, L., Liu, L., & Sherins, R. (1986) Cerebrovascular

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accident associated with testosterone therapy in a 21-year-old hypogonadal man. N

## **7. Conclusions**

The use of hormonal therapy in transsexualism is associated with appropriate physical change. Side effects in carefully monitored patients are usually few but are more likely to cause serious complications when therapy is too aggressive. This is particularly true in the FTM transsexual patients who are likely candidates for complications of dyslipoproteinemia which include premature atherogenesis, diabetes mellitus, hypertension, increased insulin resistance, and obesity. Investigators propose that initial treatment with androgen therapy which must be supraphysiological to suppress gonadotropins and virilize the patient should be kept to maximum of no more than 2 years. Following sex reassignment surgery, the dosage should be reduced by half in most patients.

It is likely to reduce not only the duration of large dosage androgen therapy but also the potential risk of endometrial hyperplasia and uterine carcinoma. The role of the concerned physician is to be fully aware of potential risk of this therapy so as to adjust treatment and minimize potential complications.

#### **8. References**


The use of hormonal therapy in transsexualism is associated with appropriate physical change. Side effects in carefully monitored patients are usually few but are more likely to cause serious complications when therapy is too aggressive. This is particularly true in the FTM transsexual patients who are likely candidates for complications of dyslipoproteinemia which include premature atherogenesis, diabetes mellitus, hypertension, increased insulin resistance, and obesity. Investigators propose that initial treatment with androgen therapy which must be supraphysiological to suppress gonadotropins and virilize the patient should be kept to maximum of no more than 2 years. Following sex reassignment surgery, the

It is likely to reduce not only the duration of large dosage androgen therapy but also the potential risk of endometrial hyperplasia and uterine carcinoma. The role of the concerned physician is to be fully aware of potential risk of this therapy so as to adjust treatment and

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a review of treatment regimens, outcomes, and adverse effects. Journal of Clinical

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Monihan, M., Vormohr, J., & Zevin, B. (2001). Protocols for hormonal reassignment of gender. San Francisco: San Francisco Department of Public Health. Retrieved January 1, 2005, from http://www.dph.sf.ca.us/chn/HlthCtrs/HlthCtrDocs/

steroid hormones on regional fat depots as assessed by magnetic resonance

Effects of cross-sex hormone treatment on emotionality in transsexuals. International Journal of Transgenderism, 5. Retrieved January 1, 2005, from

surgery, 2nd ed. Philadelphia, PA: Sounders., 1305-1316.

Endocrinology & Metabolism, 88, 3467-3473.

Watertown, MA: Together Lifeworks.

TransGendprotocols.pdf

**7. Conclusions** 

dosage should be reduced by half in most patients.

minimize potential complications.

**8. References** 

413-9.


**23**

*Ireland* 

**The Role of Prophylactic Oophorectomy**

**1.1 Historical perspective of prophylactic-oophorectomy in ovarian and breast** 

Prophylactic salpingo-oophorectomy (PO) entails removal of the ovaries prior to the clinical occurrence of cancer. Prophylactic removal of the ovaries, during hysterectomy or other abdominal surgery, to prevent ovarian cancer in postmenopausal women was popularised in the 1940s by Crossen, who stated *"the involuting ovaries have fulfilled their reproductive and endocrine function. They are....vestigial structures which carry a special tendency to cancer*" (Crossen, 1942). The first report of prophylactic oophorectomy for familial ovarian cancer was in 1950 when A.M Liber described a family of five sisters and their mother, all with histologically confirmed papillary adenocarcinoma of the ovary; it was recommended that family members should undergo frequent gynaecologic screening, and that prophylactic

The role of oophorectomy in the management of breast cancer dates further back to 1889 when it was first proposed by Albert Schinzinger (Schinzinger, 1889); he observed that the prognosis for breast cancer appeared better in older women than younger women and postulated that oophorectomy would initiate atrophy of the breast and any cancer within the breast. Shinzinger suggested oophorectomy both as therapy for advanced breast cancer and prophylaxis against local recurrence, but he never actually performed the surgery; it was George Thomas Beatson who first performed a bilateral oophorectomy on a patient with metastatic breast cancer in 1895 , this was reported in the Lancet in 1896 (Beatson, 1896). A subsequent report detailed that this patient experienced remission of her disease and lived another four years. Beatson hypothesized that oophorectomy caused fatty degeneration of the malignant cells accounting for its beneficial effect in breast cancer (Beatson, 1896; Thomson, 1902). An English surgeon, Stanley Boyd performed the first oophorectomy as adjuvant breast cancer therapy in 1897 (Boyd, 1897). He commented "my working hypothesis is that internal secretion of the ovaries in some cases favors the growth of the cancer" and subsequently reported that that one third of breast cancer patients benefited from oophorectomy as adjuvant therapy (Boyd, 1900), in this way the rationale for hormonal treatment of breast cancer was first implied. In 1968 Feinleib observed that

**cancers before the era of BRCA1/BRCA2 testing** 

oophorectomy should be considered (Liber, 1950)

**1. Introduction** 

**in the Management of Hereditary**

A.J. Lowery and K.J. Sweeney

**Breast & Ovarian Cancer Syndrome** 

*Department of Surgery, National University of Ireland Galway,* 

