Chronic pelvic pain among transgender men and gender diverse adults assigned female at birth.

Diana M. Tordoff and Juno Obedin‐Maliver conceived of the study design and methodology and had access to all data. Diana M. Tordoff performed and verified all analyses and wrote the original manuscript draft, with support from Juno Obedin‐Maliver. Mitchell R. Lunn, Annesa Flentje, Zubin Dastur, Micah E. Lubensky, Matthew Capriotti, and Juno Obedin‐Maliver contributed to data collection. All authors provided input on data interpretation and provided manuscript edits.

This analysis included 2579 TGD participants assigned female at birth aged 18–80 years old (median age 27.6, interquartile range 23–34). There were 572 (22%) participants who selected at least one non‐White race and ethnicity, and 381 (15%) who selected multiple races and ethnicities. Most participants selected more than one gender (60%) and sexual orientation (53%). Participants most commonly identified as non‐binary (58%) and/or transgender man (47%). In terms of sexual orientation, most participants identified as queer (62%) and/or bisexual (34%). Most participants reported annual incomes below $20,000 (50%) or between $20,000 and $39,999 (22%). Additional participant characteristics are reported in Table  1 . Study participant characteristics, transgender men and gender diverse people assigned female at birth, The Population Research in Identity and Disparities for Equality (PRIDE) Study, 2020–2022, N  = 2579. Percentages may sum to greater than one since participants were able to select more than one category. We were unable to calculate p values for these overlapping groups defined by race, ethnicity, gender, or sexual orientation. Overall, 457 (18%) participants reported CPP. Chronic pain was most commonly reported in the pelvis ( n  = 356, 78%), followed by the groin ( n  = 180, 39%) and genitals ( n  = 96, 21%). Nearly all ( n  = 440, 96%) participants who reported CPP also reported chronic pain at another location, including the lower back ( n  = 318, 70%), hips ( n  = 266, 58%), abdomen ( n  = 196, 43%), and buttocks ( n  = 103, 23%). The prevalence of CPP was highest among participants aged 30–49 (20%) and 60+ (24%) as well as among participants who were Native American/Alaska Native (27%), Middle Eastern/North African (30%), or who reported multiple racial or ethnic identities (21%). The prevalence of CPP was highest among individuals with lower incomes (20.2% among individuals with incomes <$20,000 vs. 11.7% for incomes ≥$100,000, p  = 0.021). Participants with CPP were more likely to have had a hysterectomy (14% vs. 11%, p  = 0.041) or oophorectomy (11% vs. 8%, p  = 0.048). CPP correlates included inflammatory bowel disease, irritable bowel syndrome, kidney stones, pelvic inflammatory disease, PCOS, uterine fibroids, current hormonal IUD use, prior pregnancy, and vaginal delivery (Table  2 ). Individuals with CPP reported a high prevalence of irritable bowel syndrome (37%), PCOS (20%), and uterine fibroids (9%). Menses in the past year, current non‐IUD hormonal contraceptive use, and Cesarean delivery were not associated with CPP. Correlates of chronic pelvic pain among transgender men and gender diverse people assigned female at birth, The Population Research in Identity and Disparities for Equality (PRIDE) Study, 2020–2022, N  = 2579. Abbreviations: GAD‐7, Generalized Anxiety Disorder 7‐item survey; IUD, intrauterine device; PHQ‐9, Patient Health Questionnaire‐9; PTSD, post‐traumatic stress disorder. Restricted to participants without a prior hysterectomy. CPP was associated with poor mental health. Participants with CPP had a high prevalence of PTSD diagnosis (51%), severe depression symptoms (42%; PHQ‐9 ≥ 15), and severe anxiety symptoms (25%; GAD‐7 ≥ 15). In terms of healthcare utilization and access, participants with CPP were more likely to have public insurance (23% vs. 15%, p  < 0.001), more likely to see a primary care provider in the past year (90% vs. 85%, p  = 0.002), and less likely to see a provider who specializes in sexual and reproductive health (60% vs. 71%, p  < 0.001). Fifty‐two percent ( n  = 1334) of participants currently used testosterone, 37% ( n  = 946) had never used testosterone, 5% ( n  = 122) formerly used testosterone, and 7% ( n  = 177) were missing data on testosterone use (Table  2 ). The median duration of testosterone use was 4 years (interquartile range (IQR) 2–7 years, range 19 days to >30 years). The prevalence of CPP was 16% among individuals currently using testosterone, 19% among individuals who had never used testosterone, and 23% among individuals who formerly used testosterone (Table  2 ). After adjusting for age and prior hysterectomy, current testosterone use was associated with a 21% lower prevalence of CPP (adjusted prevalence ratio [aPR] 0.79, 95% confidence interval [CI]: 0.65–0.96; Table  3 ). In addition, current testosterone use was associated with 53% lower prevalence of CPP among individuals with a prior hysterectomy (aPR 0.47, 95% CI: 0.27–0.80). Subgroup‐specific analyses for individuals with inflammatory bowel disease, irritable bowel syndrome, kidney stones, pelvic inflammatory disease, PCOS, uterine fibroid, or a prior oophorectomy were not statistically significant, likely due to a large reduction in sample sizes. However, the point estimates for the aPRs were all below 1.0 and suggestive of a protective effect of current testosterone use for individuals with these specific diagnoses. Association between current testosterone use and chronic pelvic pain among transgender men and gender diverse people assigned female at birth, The Population Research in Identity and Disparities for Equality (PRIDE) Study, 2020–2022. Poisson regression excludes 177 participants who were missing data on testosterone use. Abbreviation: aPR, adjusted prevalence ratio. CI, confidence interval. PR, prevalence ratio. Adjusted for age and prior hysterectomy. Lastly, we conducted exploratory longitudinal analyses among participants who were testosterone naïve at baseline, reported initiating testosterone on a consecutive survey, and who had 2 or more years of data available (Figure  1 ). There were 79 participants who met these criteria: 53 with 3 years of available data and 16 with 2 years of available data. At baseline, prior to initiating testosterone, 13 (16%) participants reported CPP. Among those who reported CPP at baseline, 62% ( n  = 8/13) reported persistent CPP in the first year of testosterone use, and 56% ( n  = 5/9) reported persistent CPP in the second year of testosterone use. Among those who did not report CPP at baseline, seven (11%) participants reported new‐onset CPP within the first 2 years of initiating testosterone, 6% in year 1 ( n  = 4/66) and 9% in year 2 ( n  = 4/44). Overall, there were 15 participants who reported any CPP after initiating testosterone, eight (56%) who had reported CPP prior to testosterone initiation, and seven (47%) who reported new‐onset CPP. Longitudinal analysis of chronic pelvic pain among transgender men and gender diverse participants before and after testosterone initiation, The Population Research in Identity and Disparities for Equality (PRIDE) Study, 2020–2022.

We used 3 years of data, 2020–2022, from The Population Research in Identity and Disparities for Equality (PRIDE) Study, a prospective cohort study of sexual and gender minority adults in the United States. Our analysis included TGD participants assigned female at birth, including transgender men, transmasculine, non‐binary, and genderqueer individuals as well as those who reported additional write‐in gender identities. Participants self‐reported data on race/ethnicity, gender identity, sexual orientation, sex assigned at birth, and annual household income. Participants could select multiple response options for race/ethnicity, gender, and sexual orientation. Chronic pain was defined as self‐reported persistent or recurrent pain present for the last 3 months or longer in specific areas of the body. We defined CPP to include participants who reported pain in their pelvis, right or left groin, and/or genitals using a modified version of the Michigan Body Map. 23 The Michigan Body Map has been validated to reliably assess pain location for individuals experiencing chronic pain, but it has not been specifically validated for CPP. 23 , 24 We categorized participants as never, current, and former testosterone users. Current testosterone use was assessed in the 2020–2022 annual questionnaires and included participants who, at the time, indicated they were currently taking testosterone (of any formulation, including gel, injection, or patch) for gender affirmation. To differentiate participants who had never used testosterone from participants who formerly used testosterone, we also incorporated participants’ responses to a baseline survey that assessed participants' lifetime testosterone use. Duration of testosterone use was calculated based on the participant's self‐reported month and year of initiating testosterone. Participants self‐reported prior surgical procedures, including hysterectomy, oophorectomy, metoidioplasty, and phalloplasty. We considered several conditions that are associated with pelvic pain, including self‐reported diagnosis with inflammatory bowel disease, irritable bowel syndrome, kidney stones, pelvic inflammatory disease, polycystic ovary syndrome (PCOS), and uterine fibroids. Although endometriosis and interstitial cystitis are common diagnoses among people with CPP, we did not ask about these prior diagnoses. We also examined prior pregnancies and vaginal or Cesarean birth. Participants reported if they had menstruated at least once in the past year, current non‐hormonal intrauterine device (IUD) use, hormonal (i.e., levonorgestrel) IUD use, and non‐IUD hormonal contraceptive use (including oral contraceptives, transdermal patch, vaginal rings, medroxyprogesterone acetate injections, and etonogestrel implants). Mental health measures included currently being diagnosed with post‐traumatic stress disorder (PTSD). Depressive symptoms in the past 2 weeks were assessed using the Patient Health Questionnaire‐9 (PHQ‐9) 25 ; anxiety symptoms in the past 2 weeks were assessed using the Generalized Anxiety Disorder 7‐item survey (GAD‐7). 26 We restricted our analysis to participants who responded to chronic pain questions. Our primary analysis was cross‐sectional. For participants with multiple years of available data, we used their first available survey responses. We used counts, proportions, and chi‐squared tests to examine correlates of CPP. We used multivariable Poisson regression with robust standard errors to estimate the association between current testosterone use and CPP relative to no testosterone use (both never and former use), adjusted for age and prior hysterectomy. To explore potential etiology‐specific associations, we examined the association between current testosterone use and CPP among subgroups of participants with diagnoses of inflammatory bowel disease, irritable bowel syndrome, kidney stones, pelvic inflammatory disease, PCOS, and uterine fibroids as well as among those who reported a prior hysterectomy or oophorectomy. We conducted exploratory longitudinal analyses to examine patterns of self‐reported CPP before and after testosterone initiation. We included participants with 2 or more consecutive years of data who were testosterone naïve at baseline with at least 1 subsequent year of data in which they reported current testosterone use. Because some transgender individuals may stop and restart testosterone use based on personal preference as well as due to structural barriers to consistently accessing gender‐affirming hormones, we confirmed participants had no prior testosterone use using data from a baseline questionnaire that assessed lifetime testosterone exposures. All analyses were conducted in R version 4.2.1. This study received ethical approval from the University of California, San Francisco, Stanford University School of Medicine, and WCG Institutional Review Boards.

In our study, nearly one in five TGD people assigned female at birth experience CPP. Although testosterone use was associated with a lower prevalence of CPP, some TGD individuals experienced new‐onset pelvic pain after testosterone initiation. The relationship between CPP and testosterone use is complex and warrants future research. Testosterone gender‐affirming hormone therapy may reduce or resolve pelvic pain for some individuals; while for others, testosterone may be associated with changes to the urogenital and reproductive environment that cause new‐onset pelvic pain. Given the significant impact that CPP can have on mental health and quality of life, there is an urgent need for future research to examine the role of testosterone in specific underlying etiologies of CPP and to identify potential therapies.

In our large national study, we observed that CPP is common among TGD people assigned female at birth. The prevalence of self‐reported CPP was 18%, similar to what has been reported among cisgender women (6%–27%). 9 We used multiple analytic approaches to examine the association between testosterone use and CPP. In a cross‐sectional analysis, after adjusting for age and prior hysterectomy, testosterone use was associated with a 21% lower prevalence of CPP. Longitudinal analyses among a subset of TGD people who had CPP at baseline and were initiating testosterone for the first time found that the CPP resolved for a third of individuals after testosterone initiation. In addition, approximately one in 10 participants experienced new‐onset CPP after starting testosterone. These findings are similar to a recent retrospective chart review, which found that 15% of testosterone‐naïve TGD people experience pelvic pain prior to testosterone initiation, 31% of whom no longer experienced pain after starting testosterone. 1 Another cross‐sectional survey found that 22% of TGD people with pelvic pain reported that their pain improved after testosterone initiation. 2 However, our study observed a lower prevalence of pelvic pain following testosterone initiation relative to prior studies (which report prevalence estimates of 36% and 72%). 1 , 10 This may be due to differences in how pelvic pain was measured across studies (e.g., chronic pain lasting 3 months or longer vs. any reported pelvic pain) as well as recruitment methods (e.g., clinical samples 1 and focused recruitment 2 of transgender individuals with pelvic pain). Taken together, these findings suggest that testosterone may reduce pelvic pain for some individuals; while for others, testosterone may be associated with changes to the urogenital and reproductive environment that cause new‐onset pelvic pain. Our findings highlight the need for future research examining the role of testosterone in known and unknown etiologies of CPP. In our study, TGD people with CPP reported a high prevalence of irritable bowel syndrome, PCOS, and uterine fibroids. The prevalence of irritable bowel syndrome observed in our study (37%) is similar to what has been reported among cisgender women with CPP (35%). 7 However, there are limited data on common underlying conditions that cause CPP among TGD people with which to compare these estimates, and it is unclear if TGD populations are disproportionately impacted by these underlying, often chronic, conditions. Histological analysis of hysterectomy specimens from transgender men find a 9%–27% prevalence of endometriosis, 5 , 6 , 8 a 2%–7% prevalence of adenomyosis, 4 , 5 , 6 a 9%–22% prevalence of ovarian cysts, 4 , 6 and a 6%–12% prevalence of leiomyomas and uterine fibroids 4 , 6 , 22 —all gynecological conditions associated with pelvic pain. However, there are no published data on other common non‐gynecological causes of CPP in TGD populations—including interstitial cystitis, centralized pain syndrome, and musculoskeletal causes—to help contextualize these rates, compare populations, and ultimately devise appropriate treatment strategies. The treatment of CPP is challenging and not always effective, and a multidisciplinary biopsychosocial approach is recommended. 7 Consistent with prior studies, we found that half of participants who experienced CPP while using testosterone reported CPP prior to testosterone initiation. 1 Therefore, CPP should not be assumed to be caused by testosterone, and clinicians should take comprehensive patient histories and assess symptoms prior to testosterone use. In fact, for some patients, testosterone may be effective at ameliorating pelvic pain. We hypothesize that testosterone may reduce cyclic pelvic pain associated with dysmenorrhea and endometriosis through ovulation suppression and cessation of menses (which typically occurs within the first 6 months for up to 85% of patients). 8 In a small cohort of 12 transmasculine adolescents who experience dysmenorrhea, initiating testosterone led to symptom recession in eight (67%) of patients but persisted in three (33%) of patients. 8 In addition, prior studies have found that persistent menses after testosterone initiation was associated with pelvic pain, suggesting that incomplete ovulation suppression (with or without amenorrhea) may be one cause of CPP. 2 Analgesics and hormonal therapies—including progestins, combined estrogen and progestins, gonadotropin‐releasing hormone (GnRH) analogs—are common treatments for CPP. 7 Danazol (a synthetic derivative of 17α‐ethinyl testosterone) is a well‐known and effective treatment for pain associated with endometriosis; however, its use in cisgender women has been discouraged due to its androgenizing side effect. 27 Danazol may be considered more acceptable among TGD patients for whom androgenizing side effects may be welcome/desired. 8 For individuals who experience new‐onset pelvic pain after testosterone initiation, there is no known mechanism by which testosterone‐associated changes to the uterus or ovaries would cause new‐onset pain. Prior studies have hypothesized that pelvic floor muscle dysfunction may be a cause of new‐onset pelvic pain in TGD individuals using testosterone. 2 Transgender‐affirming and trauma‐informed pelvic floor physical therapy and trigger point injections may be an effective and low‐risk therapy. 28 , 29 , 30 , 31 However, future studies are needed to determine if pelvic floor dysfunction plays a causative role in new‐onset pelvic pain among TGD individuals using testosterone. Some TGD people seek hysterectomy as a part of gender affirmation. However, many TGD individuals cite pelvic pain and abnormal bleeding as a reason for seeking hysterectomy. 3 , 4 Similar to prior studies, hysterectomy was slightly more common among individuals with CPP compared with those who did not report CPP (14% vs. 11%). 1 , 6 Although prior surveys suggest that hysterectomy can be effective for reducing pelvic pain for some TGD individuals, 2 there have been no long‐term follow‐up studies of recurrent pain following hysterectomy. Hysterectomy is a major, invasive procedure not desired by all TGD individuals. In addition, some TGD people have future pregnancy desires, which should be prioritized in considering treatment. 32 TGD patients seeking a hysterectomy solely for pelvic pain should be counseled about the lack of long‐term effectiveness data to predict efficacy of this intervention for resolving pelvic pain. Our study had several strengths, including a large national cohort of TGD individuals that was diverse with respect to age, gender, sexual orientation, and geography. The PRIDE Study uses a community‐engaged approach and uses sexual health modules specifically developed for gender minority populations. 33 In addition, we use multiple approaches, including cross‐sectional and longitudinal analyses, to examine the relationship between testosterone and CPP. Our study is not without limitations. We relied on self‐reported diagnoses, which may be vulnerable to recall and social desirability bias. We did not collect data on several key variables, including prior diagnosis with endometriosis, interstitial cystitis, myofascial pain, or pelvic floor tension myalgia, which are very common among people with CPP. We did not collect data on testosterone dosage, serum testosterone levels, or healthcare utilization related to CPP. Thus, for longitudinal analysis, we are unable to determine if CPP resolved spontaneously or because of other ongoing treatment.

Chronic pelvic pain (CPP) presents a major public health problem worldwide with significant impacts on quality of life. The extremely limited data regarding pelvic pain among transgender men and gender diverse (TGD) people assigned female at birth suggests that as many as 36%–72% of TGD people using testosterone experience any pelvic pain. 1 , 2 In addition, pelvic pain is the most commonly cited reason for seeking a hysterectomy other than for gender affirmation. 3 , 4 Among transgender men with a history of testosterone use seeking hysterectomies, 51%–58% report intermittent or CPP. 5 , 6 CPP has many underlying, and often co‐occurring, etiologies among people assigned female at birth. These include gynecological (e.g., endometriosis and adenomyosis, ovarian cysts, pelvic inflammatory disease, uterine fibroids, and malignancies), urological (e.g., interstitial cystitis), gastroenterological (e.g., irritable bowel syndrome and inflammatory bowel diseases), neurologic (e.g., centralized pain syndrome), and musculoskeletal causes. 7 Endometriosis, irritable bowel syndrome, and interstitial cystitis (i.e., bladder pain syndrome) are among the most common diagnoses for cisgender women with CPP. 7 The prevalence of endometriosis among transgender men ranges from 9% to 27%, 5 , 6 , 8 but there is insufficient evidence to determine if it varies from what is reported among cisgender women (6%–27%). 9 The prevalence of irritable bowel syndrome and interstitial cystitis TGD populations is unknown. The impact of testosterone on pelvic pain among TGD people is poorly understood. Some report new‐onset pelvic pain after initiating testosterone (with a median time until onset of 1 year). 1 , 10 At the same time, pain associated with endometriosis and dysmenorrhea is hypothesized to decrease after testosterone initiation due to ovulation suppression. 8 However, testosterone does not fully suppress serum estrogen 11 , 12 , 13 or ovulatory function, 14 nor does it induce amenorrhea for all individuals. 11 In addition, testosterone use causes unique changes to the reproductive environment. Small histological studies demonstrate that 80%–100% of transgender men using testosterone develop vaginal atrophy, 15 , 16 , 17 and 65%–100% develop prostate‐like glands in the vaginal epithelium. 15 , 16 , 18 , 19 Few histological studies report mixed findings on the impact of testosterone on endometrial tissues, with some reporting majority proliferative endometrial tissue and others reporting majority inactive endometrium. 4 , 5 , 20 , 21 , 22 However, the implication of these changes for CPP is unclear. In this study, we aimed to characterize the prevalence and correlates of CPP in a large national sample of TGD people assigned female at birth. We also examined the association between testosterone use and CPP using cross‐sectional and longitudinal approaches.

Dr. Obedin‐Maliver received consultation fees from Ibis Reproductive Health, Hims Inc., Folx Health Inc., Sage Therapeutics, and Upstream Inc., on topics unrelated to this work. Dr. Lunn received consultation fees from Hims Inc., Folx Health Inc., Otsuka Pharmaceutical Development and Commercialization, Inc., and the American Dental Association on topics unrelated to this work. Dr. Chen consults with Hims Inc. All other authors declare no conflicts of interest.