Prolactinoma induced by estrogen and cyproterone acetate in a male-to-female transsexual

doi:10.1016/j.fertnstert.2010.01.076

Fertility and Sterility

Volume 94, Issue 3, August 2010, Pages 1097.e13-1097.e15

https://doi.org/10.1016/j.fertnstert.2010.01.076 Get rights and content

Objective

To report a case of a microprolactinoma in a male-to-female transsexual treated with estrogens and cyproterone acetate.

Design

Case report.

Setting

Endocrinology unit in a university hospital.

Patient(s)

A 33-year-old male-to-female transsexual with prolactin level of 10 ng/mL.

Intervention(s)

Treatment with equine-conjugated estrogens (2.5 mg/day, orally) and cyproterone acetate (100 mg/day, orally) during 6 months.

Main Outcome Measure(s)

Her levels of prolactin were repeatedly found to be elevated to a maximum of 133 ng/mL, and magnetic resonance imaging (MRI) revealed a pituitary mass of 5 × 4 × 4 mm.

Result(s)

Discontinuation of the cross-sex hormone treatment did not reduce the levels of prolactin. The use of dopaminergic-agonist therapy normalized them and reduced the size of the microadenoma. After sex-reassignment surgery, she was treated with low-dose estradiol transdermal patches and presented normal levels of prolactin and appropriate levels of 17β-estradiol and testosterone with a stable image in MRI.

Conclusion(s)

We report a case of prolactinoma after treatment with equine-conjugated estrogens and cyproterone acetate. We recommend long-term follow-up observation consisting of a periodic evaluation of prolactin levels and any symptoms suggestive of hyperprolactinemia to detect as early as possible complications derived from cross-sex hormone therapy.

Section snippets

Material and methods

We report the case of a patient in whom high levels of prolactin and a pituitary mass were detected after cross-sex hormone treatment with equine-conjugated estrogens and cyproterone acetate. The patient required antidopaminergic treatment as a result.

Results

A 33-year-old genetic male diagnosed with gender identity disorder was referred to the endocrinology department of our hospital for cross-sex hormone therapy. A physical examination revealed sex characteristics corresponding to the male sex, with adult grade genital development (G5 P5) and testicular volume of 20 Prader milliliters. The patient's weight was 72 kg, height was 1.82 m (body mass index 21.7 kg/m²), and blood pressure was 125/60 mm Hg. Gynecomastia was absent. The patient denied any

Discussion

The development of hormone-related tumors in transsexual patients receiving treatment with cross-sex hormone therapy is infrequent. The probability of developing such tumors is known to increase proportionally with the duration of the treatment and with the age of the patient. Among male-to-female transsexuals, cases of breast and prostate cancer have been reported, but very few reports of prolactinomas have been published (1), despite the considerable frequency of pituitary adenomas in the

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Estrogen-induced prolactinoma in a man
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Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration: a morphologic study
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Lactotroph hyperplasia in an estrogen treated male-to-female transsexual patient
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There are more references available in the full text version of this article.

Cited by (38)

Person-centered cancer genetic counseling for transgender and gender diverse patients
2023, Principles of Gender-Specific Medicine: Sex and Gender-Specific Biology in the Postgenomic Era
Low-Dose Cyproterone Acetate Treatment for Transgender Women
2021, Journal of Sexual Medicine
Citation Excerpt :
It should be noted that a possible detrimental role of the estradiol treatment in this context cannot be ruled out, given that serum estradiol levels were slightly higher in the high-dose group. Hyperprolactinemia associated with hormone-affirming therapy in transgender women has traditionally been attributed to the use of supra-physiologic doses of estrogen.26 There are accumulating data indicating that hyperprolactinemia is induced mainly by the CPA component of the hormone treatment.10,27
Transgender women with intact gonads receive lifelong hormonal treatment to suppress physiologic androgen production, the optimal efficacious and safe cyproterone acetate (CPA) dose has not been established.
To assess the effectiveness and safety of low-dose (10–20 mg/day) compared with high-dose (50–100 mg/day) CPA treatment.
We conducted a historical cohort study of transgender women treated at a tertiary center for transgender health.
Serum levels of testosterone, estradiol, prolactin, gonadotrophins, liver enzymes, and lipids.
There were 38 transgender women in the low-dose group and 26 in the high-dose group. Age (median 24.9 years, interquartile range [IQR] 21–30 vs 25 years, IQR 19–35) and follow-up time (median 12 months, IQR 6–23 vs 15 months, IQR 12–36) were similar in the low- and high-dose groups, respectively. Serum gonadotropins and testosterone were suppressed to a similar level at all time points in both groups. Prolactin levels increased significantly in both groups, however, with a more substantial increase in the high- vs the low-dose group (804 ± 121 vs 398 ± 69 mIU/ml at 12 months, respectively, P = .004). Total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride levels were not significantly affected by the dose.
We suggest an adjustment of current clinical practice guidelines to recommend lower doses of CPA for the treatment of transgender women.
This is the first demonstration that low-dose CPA treatment of transgender women is effective. Limitations include a relatively small sample and retrospective study design.
Low-dose CPA treatment of transgender women is as effective as high-dose treatment and possibly safer.
Zohar NE, Sofer Y, Yaish I, et al. Low-Dose Cyproterone Acetate Treatment for Transgender Women. J Sex Med 2021;18:1292–1298.
Primary and Preventative Care for Transgender Patients
2019, Comprehensive Care of the Transgender Patient
Hormone Treatment for the Adolescent Transgender Patient
2019, Comprehensive Care of the Transgender Patient
Hormonal treatment of male to female transgender
2018, Encyclopedia of Endocrine Diseases
Transgenderism is an umbrella term for those whose gender identity/gender expression differs from what is usual for the sex assigned at birth. Gender identity/expression is not necessarily binary. Transgender people experience the discrepancy between the body and their gender identity as mental distress. They seek to adapt their bodies to their gender identity by means of hormonal and surgical treatment. Transgenderism has moved from the margins of medicine to an accepted medical issue. Guidelines for its hormonal treatment have been developed.
Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents
2017, Journal of Sexual Medicine
Citation Excerpt :
Because of these potent effects and the high costs of GnRHas, CA is used in our center in adolescents who already have established secondary sexual characteristics (Tanner stage ≥ 4) to alleviate distress before the addition of estrogens. Increases of prolactin levels and stimulatory effects on meningiomas and prolactinomas have been reported.16,17 According to the 2009 Endocrine Society clinical practice guideline, puberty-suppressing therapy in transgender adolescents can be associated with cross-sex hormones (CSHs) from at least 16 years of age.18
Cyproterone acetate (CA) is an antiandrogenic progestin commonly used in adult transwomen to suppress endogenous androgens, often in combination with estrogens to induce feminization.
To assess the (side) effects and biochemical changes of CA alone and in combination with estrogens in adolescent trans-girls.
This study was a retrospective analysis of clinical and biochemical data from 27 trans-girls who presented at Tanner stage G4 and were treated with CA monotherapy for at least 6 months (mean = 12 months) and then in combination with incremental doses of estrogens (CA + E; mean = 16 months). Statistical analysis of data included paired or unpaired Student t-test or Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate.
Anthropometrics, reported beneficial and side effects, safety parameters, and hormone levels.
Physical changes included decrease of facial and non-facial hair growth. One third showed breast development under CA (Tanner stages B2–B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5% respectively, during CA + E. Reported side effects during CA and CA + E were breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes were observed. Main safety parameters showed the following changes. Hemoglobin and hematocrit decreased and liver enzymes transiently and modestly increased during CA. Triglycerides and cholesterol levels slightly decreased during CA but returned to baseline during CA + E; glucose metabolism was unaffected. Relevant hormonal changes included a decrease in gonadotropins during CA + E and in total and free testosterone levels throughout treatment. Prolactin levels increased during CA and were restored during CA + E.
CA produced modest feminizing effects in trans-girls and therefore might be a valuable alternative in situations in which gonadotropin-releasing hormone analogues are not the treatment of choice and/or are not reimbursed.
This is the first study to report on the effects of CA in the treatment of trans-girls and one of the few to report on the use of estrogens in this population. Limitations are the modest sample size and the retrospective nature of this study.
Treatment with CA in late-pubertal trans-girls overall was safe and well tolerated and induced mild clinical and biochemical feminizing changes. Rapid further feminization was observed with incremental doses of E.
Tack LJW, Heyse R, Craen M, et al. Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents. J Sex Med 2017;14:747–757.

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: K.G-M. has nothing to disclose. A.M-G. has nothing to disclose. M.R. has nothing to disclose. M.G-B. has nothing to disclose. A.H-M. has nothing to disclose.

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Case reportProlactinoma induced by estrogen and cyproterone acetate in a male-to-female transsexual

Objective

Design

Setting

Patient(s)

Intervention(s)

Main Outcome Measure(s)

Result(s)

Conclusion(s)

Section snippets

Material and methods

Results

Discussion

J Steroid Biochem Mol Biol

Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience

J Clin Endocrinol Metab

Estrogen-induced prolactinoma in a man

J Clin Endocrinol Metab

Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration: a morphologic study

Arch Pathol Lab Med

Lactotroph hyperplasia in an estrogen treated male-to-female transsexual patient

J Clin Endocrinol Metab

Case report
Prolactinoma induced by estrogen and cyproterone acetate in a male-to-female transsexual