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Pelvic pain in transgender men taking testosterone: Assessing the risk of ovarian cancer

Harris, Miles MS, BSN; Kondel, Lauren MS, BSN, FNP-BC; Dorsen, Caroline PhD, MSN, FNP

doi: 10.1097/01.NPR.0000520423.83910.e2
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Abstract: Some guidelines on care for transgender men taking testosterone recommend oophorectomy to prevent ovarian cancer, while others recommend following guidelines for females. A review of the literature finds no strong evidence that transgender men are at increased risk for ovarian cancer. In transgender men taking testosterone without other risk factors, oophorectomy to prevent cancer is unnecessary.

Miles Harris is an NP at the Comprehensive Health Program, Mount Sinai Institute for Advanced Medicine, New York, N.Y.

Lauren Kondel is an NP at New York University, New York, N.Y.

Caroline Dorsen is an assistant professor at Meyers College of Nursing, New York University, New York, N.Y.

The authors have disclosed that they have no financial relationships related to this article.

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Case study

Mr. L is a 30-year-old transgender man presenting to his NP for routine primary care. He reports that he has been experiencing pelvic pain for several months. Mr. L tells the NP he has heard that transgender men have an increased risk for ovarian cancer, and he is worried that this is the cause of his pain.

Mr. L describes his pain as dull, achy, generalized suprapubic pain, lasting a few minutes to a few hours at a time. Sometimes, the pain radiates to his back. Mr. L cannot identify a relationship between the pain and his diet, sexual activity, urinary or bowel habits, exercise, or stress. His last menstrual period was 6 years ago, approximately 4 months after initiating testosterone therapy. Mr. L has had no vaginal bleeding since then. He denies genital lesions, vaginal discharge, dyspareunia, and dysuria. Mr. L sometimes takes ibuprofen for pain, which provides moderate relief.

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Patient history

Mr. L has a medical history of depression and anxiety, for which he takes sertraline and sees a psychotherapist weekly. He has taken testosterone since age 24 and currently self-injects testosterone cypionate I.M. every 2 weeks. Mr. L had male chest reconstruction (bilateral mastectomy) at age 26 without complication and an appendectomy at age 8.

Mr. L is in a nonmonogamous relationship with his cisgender (nontransgender) male partner of 3 years, and both are sexually active with transgender and cisgender partners outside of their relationship (see Transgender glossary). They both use condoms when having sex with partners outside their relationship but do not use condoms with each other. Mr. L engages in insertive and receptive oral sex and receptive anal sex. The last time he had receptive vaginal sex was 4 years earlier. Mr. L denies a history of sexually transmitted infections and has never been pregnant.

Mr. L drinks wine and beer two to three times per week, with three to four drinks per occasion. He quit smoking cigarettes 10 months earlier and has a seven pack per year smoking history. Mr. L smokes marijuana once or twice per week and denies other past or current drug use. He lives with his partner in stable housing and works as a social worker for the city health department. Mr. L states that he has a supportive relationship with his parents and siblings and has a strong social support system. He denies any family history of gynecologic, breast, or other cancers.

Table

Table

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Vitals/physical assessment

Mr. L was afebrile with pulse, 78 beats/minute; respiratory rate, 20 breaths/minute; and BP, 128/81 mm Hg. He is 5 ft 5 in and weighs 160 lb (72.5 kg), with a body mass index of 26.6 kg/m2. He had no apparent distress and was well developed and well nourished. Mr. L had a regular heart rate and rhythm (crisp S1 and S2 without extra sounds or murmurs) and normal respiratory effort; his lungs were clear to auscultation in all fields bilaterally.

Mr. L had a soft, nontender, nondistended abdomen, with normoactive bowel sounds present in four quadrants. No masses or hepatosplenomegaly were found. His external exam was positive for clitoromegaly without lesions or discharge, and the bimanual exam was positive for atrophic vaginal changes and friable mucosa. Mr. L's uterus was nonenlarged, with nonpalpable ovaries bilaterally.

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Labs and imaging

Mr. L's last blood work (basic metabolic panel, complete blood cell count, fasting lipid panel, free and total testosterone, and hemoglobin A1C) was performed 6 months earlier. His results were within normal limits, with the exception of total cholesterol, 210 mg/dL; high-density lipoprotein cholesterol, 35 mg/dL; and low-density lipoprotein cholesterol, 120 mg/dL. Mr. L reported that his last Pap test was performed 2 years earlier with normal results and denied a history of abnormal Pap results. His urinalysis was normal and urine testing was negative for gonorrhea and chlamydia. His urine pregnancy test was negative.

The NP advised Mr. L to make lifestyle changes (a diet and exercise regimen) to help improve his cholesterol levels, and Mr. L agreed to follow the diet and exercise regimen discussed. The NP recommended a transvaginal ultrasound, but Mr. L was reluctant. Some transgender men may find a transvaginal ultrasound to be unacceptably invasive. After further discussion, the NP concluded that a transabdominal ultrasound was an acceptable substitute, and Mr. L agreed to the test. The ultrasound found a 6 cm simple cyst located on his right ovary.

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Diagnosis

Mr. L was diagnosed with a simple ovarian cyst as the cause of his pelvic pain. As testosterone does not reliably suppress ovulation in transgender men, physiologic cysts can occur. The NP informed him that simple ovarian cysts usually resolve spontaneously, advising watchful waiting and encouraging him to follow up if the pain worsens or is accompanied by vaginal bleeding.

Mr. L remained concerned that he was at increased risk for ovarian cancer due to taking testosterone. He showed the NP some case studies about ovarian cancer in transgender men on testosterone and asked if he should have an oophorectomy to eliminate his risk of developing ovarian cancer. Mr. L had not planned on having an oophorectomy as a part of his transition but stated that he would consider this option if his risk for ovarian cancer was significant.

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Guidelines

Numerous organizations have published guidelines on primary and gynecologic care for transgender men. These guidelines are inconsistent in their recommendations regarding oophorectomy related to risk for ovarian cancer. The World Professional Association for Transgender Health (WPATH) was one of the first organizations to publish clinical guidelines on healthcare for transgender individuals.

In WPATH's most recent Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, the organization states, “Analogous to persons born with female genitalia with elevated androgen levels, testosterone therapy in female-to-male (FTM) patients may increase the risk of ovarian cancer, although evidence is limited.”1

Other prominent clinical guidelines concur with WPATH's standards in regards to risk for ovarian cancer in transgender men. The Endocrine Society's clinical practice guideline Endocrine Treatment of Transsexual Persons states that there may be an increased risk for ovarian cancer in individuals undergoing long-term testosterone therapy. The guideline recommends transgender men evaluate the risks and benefits of total hysterectomy and oophorectomy.2

Similarly, the American College of Obstetricians and Gynecologists' (ACOG) Committee Opinion No. 512, Health Care for Transgender Individuals, also reports a possible increased risk for ovarian cancer in transgender men.3 Additionally, ACOG published a Committee Opinion on adolescent care in January 2017. Committee Opinion No. 685, Care for Transgender Adolescents, states that cases of gynecologic cancers, including ovarian cancer, have been reported in transgender men taking androgen therapy. However, there are only a few reported cases and no sufficient data to conclude that androgen therapy increases the risk of gynecologic cancer. The opinion is available online (www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Adolescent-Health-Care/Care-for-Transgender-Adolescents). Gooren's “Care of Transsexual Persons” in the New England Journal of Medicine states that “...FTM transsexuals who have not undergone breast removal and oophorectomy–hysterectomy should be monitored for estrogen-sensitive cancers of the breast, endometrium, and ovaries.”4

Guidelines from The Center of Excellence for Transgender Health are the exception, stating that there is no evidence of increased risk for ovarian cancer in transgender men. Their Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People recommends following guidelines for cisgender women regarding screening for ovarian cancer.5

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Research findings

The first case reports of transgender men with ovarian cancer appeared in the literature in 2000. Hage and colleagues described two transgender men, both living in the Netherlands, who developed ovarian cancer while taking testosterone.6 They hypothesized that the administration of exogenous androgens in these patients may have had “mitogenic effects,” enhancing the action of growth factors and thereby increasing their risk for ovarian cancer. The authors concluded that salpingo-oophorectomy should be performed in transgender men who are undergoing hysterectomy.6

In 2006, Dizon and colleagues presented a case of a transgender man with ovarian cancer in the literature.7 They noted that androgen receptors are present in most epithelial ovarian cancers and may have a role in tumor progression. The authors stated, “Recommendations for bilateral salpingo-oophorectomy remain premature in the absence of a true association or even causation, as it relates to testosterone supplementation.” Nonetheless, they recommended that prophylactic bilateral salpingo-oophorectomy be considered in transgender men taking testosterone.7

Another proposed mechanism for increased risk of ovarian cancer among transgender men taking testosterone relates to polycystic ovary syndrome (PCOS). Multiple studies have found evidence for increased incidence of PCOS, previously considered to be a risk factor for development of ovarian cancer, among transgender men.8,9 Hage and colleagues cite this as an additional possible pathway leading toward an increased risk for ovarian cancer among transgender men.6 However, recent research indicates that testosterone therapy in transgender men leads to ovarian hyperplasia, but not an increase in PCOS.10,11

Previous research linking PCOS to an increased risk for ovarian cancer is now in question. A recent meta-analysis by Barry and colleagues found no significant increase in risk for ovarian cancer among patients with PCOS.12

Studies assessing morbidity and mortality among transgender men have found no increased risk for ovarian cancer. For example, Grynberg and colleagues studied ovarian histology following oophorectomy in 112 transgender men.13 All ovaries showed hyperplasia, and the majority had increased antral follicles, but none had malignant changes. Likewise, Wierckx and colleagues conducted a cross-sectional case-control study on the effects of hormone therapy, with 138 transgender men, 214 transgender women, and age- and gender-matched controls. Compared with the control groups of cisgender men and cisgender women, transgender men on testosterone therapy had no increase in cancers of any kind.14

Multiple cohort studies have found no evidence of increased gynecologic cancers in transgender men. A study of 133 transgender men found an increase of borderline statistical significance of malignancies among transgender men compared with the control group; however, none of these cancers were gynecologic.15 Asscheman and colleagues conducted a cohort study of 966 transgender women and 365 transgender men receiving hormone therapy.16

Deaths related to cancer were not significantly different in transgender patients compared with the control group. No cases of gynecologic cancers occurred among transgender men. An analysis of data from the Australian Ovarian Cancer Study by Olsen and colleagues provides the only compelling evidence concerning the increased rate of ovarian cancer in transgender men. While the authors conclude that androgen-related disorders in cisgender women do not increase the risk for ovarian cancer, they found that cisgender women who had a history of testosterone supplement use had a higher risk for ovarian cancer. The number of women reporting testosterone use who developed ovarian cancer was small (11 subjects). The implications of this finding for transgender men are unclear.17

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Mr. L's case, continued

The NP explains to Mr. L that based on the currently available evidence, transgender men do not seem to be at increased risk for ovarian cancer. His ovarian cyst will be managed in the same manner as it would be in a cisgender woman, for whom oophorectomy would not be an appropriate recommendation. As his pain is adequately controlled with over-the-counter analgesics, additional pain management is not necessary.

Mr. L remained ambivalent about whether or not he was interested in an oophorectomy as part of his gender affirmation surgery. At a subsequent visit, the NP provided counseling on the risks and benefits of oophorectomy as part of his transition care. Risks for oophorectomy include complications of surgery and anesthesia as well as a risk of postoperative adhesions and small bowel obstruction.18

The patient should also be aware that should he elect to discontinue testosterone therapy following oophorectomy, the patient would experience menopausal symptoms and have similar risks as cisgender postmenopausal women, such as for increased risk for osteoporosis.5

The NP also included a discussion of fertility in counseling regarding oophorectomy. Mr. L was not sure at the time whether he would want to have a genetic child in the future. If Mr. L were to choose an oophorectomy, his options for fertility preservation would include cryopreservation of embryos or ovarian tissue or oocyte vitrification.5 All of these choices are expensive, often not covered by insurance, and involve hormone treatments that transgender men may find undesirable.

The ability of transgender men to become pregnant following testosterone therapy is well established but understudied. A 2014 study surveyed 41 transgender men who had experienced pregnancy, 25 of whom had been taking testosterone prior to their pregnancy.19 The majority of pregnancies were conceived with the patient's own oocytes. For transgender men wishing to parent, conceiving and carrying a pregnancy may be a viable option.

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Counseling patients accordingly

As demonstrated by Mr. L, concern for increased risk of ovarian cancer exists among transgender men and their healthcare providers. Though there are several case studies of transgender men taking testosterone who developed ovarian cancer in the literature, the most current research demonstrates no strong evidence for an increased risk for ovarian cancer in this population. However, given the limited available research on this subject, additional studies are needed to confirm that transgender men taking testosterone are not at increased risk for developing ovarian cancer. NPs should counsel patients accordingly, remembering that oophorectomy remains an option should patients desire this procedure as a part of their gender affirmation surgery. Appropriate education surrounding the procedure, its risks, and its impact on future fertility should be provided.

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REFERENCES

1. Coleman E, Bockting W, Botzer M, et al Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. Int J Transgend. 2012;13(4):165–232.
2. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009;94(9):3132–3154.
3. American College of Obstetricians and Gynecologists. Committee Opinion no. 512: health care for transgender individuals. Obstet Gynecol. 2011;118(6):1454–1458.
4. Gooren LJ. Clinical practice. Care of transsexual persons. N Engl J Med. 2011;364(13):1251–1257.
5. Deutsch M. Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People. 2nd ed. San Francisco, CA: University of California; 2016.
6. Hage JJ, Dekker JJ, Karim RB, Verheijen RH, Bloemena E. Ovarian cancer in female-to-male transsexuals: report of two cases. Gynecol Oncol. 2000;76(3):413–415.
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15. Dhejne C, Lichtenstein P, Boman M, Johansson AL, Långström N, Landén M. Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PLoS One. 2011;6(2):e16885.
16. Asscheman H, Giltay EJ, Megens JA, De Ronde WP, Van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635–642.
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Keywords:

oophorectomy; ovarian cancer; pelvic pain; testosterone therapy; transgender men

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