Introduction: Pelvic Pain
Pelvic pain in transgender men can be a clinical challenge and has a broad differential diagnosis. Pelvic pain less than 6 months of duration is considered acute. Chronic pelvic pain, which is continuous or episodic pain in the lower abdomen or pelvis lasting more than 6 months, has a large differential. History is a critical component to assessment and diagnosis. Key to the history is a detailed description of pain including onset, precipitating and palliating features, quality, radiation, severity and timing. A pain diary can be helpful to elucidate pain pattern and features and there are many available online.
The general approach to the workup of pelvic pain in transgender men is similar to that for non-transgender women. An anatomic approach to history gathering that considers urological, gynecologic, gastrointestinal, musculoskeletal, and psychological components is critical. Specific etiologies may be multifactorial, such as post-surgical adhesions with or without gastrointestinal symptoms, or endometriosis and/or pelvic floor muscle dysfunction. It is also critical to assess quality of life impact and determine what the patient would consider a favorable outcome. Most evaluation and treatment guidelines stress that chronic pelvic pain can be a diagnostic and therapeutic challenge, and success will depend on comprehensive and customized evaluation and multidisciplinary care.[2,3]
Specific medical etiologies to consider in transgender men include: atrophic or infectious vaginitis, cervicitis, cystitis, STIs, adhesions, post-surgical sequelae, musculoskeletal disorders, and neurogenic. Specific behavioral etiologies to consider include: depression, history of emotional trauma (including sexual assault or abuse, adverse childhood events), and post-traumatic stress disorder. The use of testosterone has a dose dependent effect on vaginal tissue by inducing a hypoestrogenic state which promotes atrophy, increases vaginal pH and thus increases the risk of vaginitis and cervicitis. Additionally, transgender men may have decreased access to or utilization of screening and therefore treatment for cervicitis and sexually transmitted infections.[5-7] Prior surgery may cause adhesions, scar tissue, bladder dysfunction, or nerve injury, which may lead to a lack of visceral mobility and contribute to pain. It is unclear to what extent post-surgical adhesions cause pain independently, or via secondary mechanisms such as constriction or incarceration of other organs. Transgender men who have pelvic pain after hysterectomy but have retained one or both ovaries/gonads should be screened for a gonadal pathology. The interaction between a genotypic female skeleton and increased muscle mass as a result of testosterone therapy may result in changes in postural carriage. Additionally, recent and/or history of sexual trauma may be exacerbated among those with gender minority status. Engaging with medical professionals can be re-traumatizing in this setting; in all cases a trauma informed approach should be taken.
Taking a pelvic pain history
The initial history should include a menstrual history including age of onset, frequency of menses or cyclical menstrual-like symptoms even if amenorrheic, duration of menses, last menstrual period, and if amenorrheic, for how long. Also assess for use of pain medication, and any association with testosterone dosing cycles. A comprehensive sexual history, including assessing for specific behaviors with other individuals such as (vaginal-vaginal), vaginal or anal or receptive penile sex, recognizing that many transgender men may engage in receptive vaginal sex. Assess for potential risk of pregnancy and ectopic pregnancy; transgender men who have receptive vaginal sex with a partner with sperm are at risk for unintended pregnancy, including ovulation and conception without preceding menstrual bleeding. Also note any history of pelvic inflammatory disease. A surgical history should note for history of an open, laparoscopic or vaginal approach to inform suspicions of scar tissue and adhesions and subsequent symptomatology. Note any specific risks such as a ruptured appendix or history of pelvic inflammatory disease (PID). Other history should include screens for adverse childhood events, current domestic violence, and for substance use and overuse, including tobacco.
On exam assess for involvement of various abdominopelvic organs, including a check for costo-vertebral angle tenderness, palpation of the abdominal wall, noting any particular tenderness along prior surgical scars or point tenderness along scars or the abdominal wall in general. Palpate the bladder for localized sensitivity, and palpate the abdomen for visceral organ involvement. Consider a speculum exam only if clearly indicated, noting vaginal discharge or any evidence of vaginitis, and assess the general condition of vaginal tissues and the cervix. If a pelvic exam is necessary, consider starting with a pediatric speculum. If a bimanual exam is performed, note any cervical, adnexal or ovarian tenderness to palpation. Also assess sensation in the vulvar area with cotton tipped nerve testing as well as sharp/dull differentiation, and examine of the pelvic floor via palpation of the obturator internus (two-digit exam with palpation of muscles at 4 to 5 o'clock and 7 to 8 o'clock; pain on flexion of the two fingers at these locations suggests pelvic floor dysfunction). Also if indicated consider a rectal exam, noting masses, tenderness, or hardened stool. Laboratory testing includes a urinalysis and culture, testing for Chlamydia and gonorrhea, vaginal pH, vaginal wet mount and KOH prep, and possibly a vaginal culture. A pregnancy test should be considered, however some patients who are not sexually active with someone capable of insemination may be offended by the suggestion of this test. It is best to explain to patients in advance that this test is part of a standard protocol, and if it is certain that pregnancy is not possible based on sexual behaviors, a pregnancy test may be omitted. Imaging should be performed using transabdominal or transvaginal ultrasound; in those men who have had a vaginectomy, a transrectal ultrasound may be an option. Some transgender men may decline vaginal ultrasound and/or bimanual exams due to potential exacerbation of gender dysphoria. These patients should not be forced to undergo a pelvic examination. In these cases proceed with an abdominal exam as well as laboratory and transabdominal ultrasound for the initial workup. Specifically for transgender men, critical components of the assessment include timing of pain and associated symptoms in relation to initiation of testosterone therapy, moliminal timing (symptoms in relation to an expected menstrual cycle) even in the presence of amenorrhea, and a detailed history of prior surgeries and related organ inventory.
Testosterone-induced dyspareunia, vaginitis, and cervicitis
The use of testosterone often results in estrogen deficient, atrophic vaginal tissues akin to a post-menopausal state in cisgender women.[11-13] These atrophic vaginal tissues represent a decline in tissue resilience, skin barrier function, and increased susceptibility to altered microbial environment and resistance which may result in bacterial vaginosis, cystitis, or cervicitis. Additionally, thin atrophic vaginal tissues are more susceptible to traumatic irritation from friction and sexual contact, which may result in atrophic dyspareunia or vaginitis. Symptoms are often described as "rough" "sand-paper" and "burning" or "dry" vaginal irritation. Visual inspection consistent with atrophy will demonstrate thin pale tissues, a loss of rugae, loss of elasticity, friability, and dryness. It is also possible to find hyperemic, deep red vaginal tissue. Bacterial vaginosis is more common in the estrogen-deprived state. Wet mount, vaginal culture, vaginal pH and STI testing can aid in directing treatment. Interstitial cystitis should be considered when infectious causes have been rules out and symptoms localize to the urinary bladder. Vaginal estrogen to treat underlying atrophy may be warranted and a short course may be successful in restoring comfort. Patients may be reassured that vaginal estrogen is associated with minimal systemic absorption and should not interfere with the desired effects of Testosterone. Other therapeutic approaches may include vaginal lubricants or vaginal moisturizers.
Cyclic symptoms relating to testosterone dosing
Transgender men on testosterone may complain of pain that is associated with cyclical testosterone dosing, pelvic, and/or vaginal pain with penetration (with penis, fingers, dildo, etc.), or orgasmic pain. The etiology of post-testosterone administration cramping is unclear. In one cross-sectional study 20% of respondents had a hysterectomy to decrease post-testosterone cramping and another 22% to stop "extreme bleeding and cramping." Trauma informed care can be effective, as are other treatments used for chronic pelvic pain such as pelvic floor therapy, vaginal lubrication with unscented products, or the use of tricyclic antidepressants.
Co-occurring mental health conditions
As with any pain syndrome, patients with chronic pelvic pain should be evaluated for depression and post-traumatic stress disorder (PTSD). These conditions may be simultaneously present in up to 35% of non-transgender female patients with chronic pelvic pain. Multiple studies link adverse childhood events with increased incidence of chronic pain and depression. Pre-existing depression may exacerbate pelvic pain. Conversely, pelvic pain and living with a chronic pain condition may result in depression. A high percentage of those who have undergone sexual assault develop PTSD, and many of those who have PTSD may develop pelvic floor muscle dysfunction and pain.[17,18] The presence of pelvic pain as well as the related workup and evaluation may trigger PTSD, especially if such trauma relates to a prior sexual assault or otherwise involves the lower abdomen and pelvis. These symptoms may be even greater in transgender men for whom examination of genital and reproductive organs may be particularly challenging and triggering of gender dysphoria, and result in avoidance of pelvic exams. Collaboration with a specialist in mental health can be an important adjunct to pathophysiological evaluation and treatment.
The initial approach to management should include NSAIDS, with other pain management medications used as indicated and appropriate. Changing to a more even testosterone transdermal testosterone regimen, or adding a progestogen such as the levonorgestrel IUD may address underlying hormonal causes.
Role of hysterectomy
In addition to non-surgical approaches, in some cases hysterectomy may have a role in the management of pelvic pain. Depending on the preferences and reproductive goals of an individual patient, gynecologists may revise their therapeutic approach to consider hysterectomy earlier than they might in non-transgender women (Grading: X C S). At the same time hysterectomy should not be viewed as a cure-all, and in some cases is not effective in improving pain. For this reason, transgender men with pelvic pain must be evaluated on a case-by-case basis due to the lack of evidence-based guidance at this time. Decision to perform oophorectomy should be based on the etiology of pelvic pain, presence of comorbidities, future fertility desires, and any future plans to stop taking testosterone.
Management of specific symptoms and syndromes
If pain is vulvar and there are no identifiable lesions or infections, Consider the use of topical 2-5% topical lidocaine placed on soaked cotton-ball and left in the vestibule overnight for general pain relief, or for 30 minutes prior to sexual activity as desired.
If pain is vulvar and exam is consistent with vaginal atrophy in the setting of testosterone administration, consider a short course of vaginal estrogen in doses and administration similar to that used for post-menopausal non-transgender women. Patients who are uncomfortable with intravaginal use may be instructed to place treatment cream on their external genitalia. Choice between tablets, creams, and rings depends on patient preference and formulary considerations.
If pain is triggered by pelvic floor muscle palpation, consider referral to pelvic floor physical therapy, pelvic floor relaxation exercises, and even guided instruction on massage using self or partner's fingers or a massage tool.
If pain is abdominal, present in the abdominal wall or associated with abdominal scar tissue, consider treatment with 1% lidocaine instilled at trigger points in repeated administration.
If transvaginal ultrasound is required, consider a low-dose benzodiazepine such as lorazepam 0.5mg orally, 30 minutes prior to the procedure, in coordination with administration of 2-5% lidocaine ointment applied to the vulva and vagina 10 minutes prior to the procedure. Some patients may feel safer and more comfortable placing the ultrasound probe intra-vaginally themselves. These approaches may also be used in advance of a pelvic examination.
Introduction: Persistent menses and unexpected vaginal bleeding
Many transgender men chose not to undergo hysterectomy, oophorectomy and/or gender affirming genital procedures.[19,21,22] For transgender men of reproductive age undergoing transition without hormones, or those whom have used testosterone and later discontinued it due to unwanted side effects such as balding, menses would be expected to be within standard reference ranges from 21-35 days between cycles with no inter-menstrual bleeding and lasting on average 2-6 days and ceasing on average at age 49. Variation from these ranges warrants further gynecological investigation.
For those transgender men using physiologic doses of testosterone, cessation of menses is expected, typically within 6 months. Cessation of menses is driven by a combination of testosterone induced ovulation suppression, which may be incomplete, and endometrial atrophy. However, the time to cessation of menses may vary. Factors that affect time to cessation of menses likely include: dose of testosterone, route of administration, frequency of testosterone administration, presence and functioning of ovaries, body habitus, and the presence of other structural or non-structural medical conditions of the uterus or ovaries. Transgender men with a history of abnormal cycles prior to initiating testosterone (e.g. frequent cycles, heavy irregular bleeding) may have underlying pathology, which could result in a prolonged or complicated path to cessation of menses once on testosterone. Therefore in patients with risk factors for endometrial hyperplasia and a degree of clinical suspicion, evaluation for and elimination of known causes of irregular bleeding should be considered concurrent with testosterone administration; those with pre-existing amenorrhea or oligomenorrhea may require evaluation for endometrial abnormalities prior to initiating testosterone. This includes ruling out pregnancy in transmen who are sexually active with partners who produce sperm.
Abnormal uterine bleeding (AUB) may be considered present in those who have continued bleeding after 6-12 months of male-range testosterone levels and suppressed LH and FSH. AUB may be related to a variety of structural and non-structural causes. These causes can be summarized by the internationally recognized Federation of Gynecology and Obstetrics (FIGO) PALM-COEIN classification system. Structural causes of AUB include: endometrial polyps, adenomyosis, leiomyomata, endometrial hyperplasia, or malignancy. As a group these are best evaluated with imaging and endometrial biopsy. Despite prior suggestions that endometrial cancer risk may be increased in transgender men on testosterone, longer-term data do not support this risk. Non-structural causes of AUB include: pregnancy, coagulopathy, ovulatory dysfunction, endometrial, or iatrogenic causes. While the gold standard for pelvic imaging is transvaginal ultrasound, other approaches such as a sonohysterogram, transabdominal ultrasound, CT scan, or MRI may be warranted. Both structural and non-structural causes should be investigated in consultation with a gynecologist. The decision to pursue transvaginal ultrasonography or endometrial biopsy should not be taken lightly in transgender men who may find these procedures invasive. Noninvasive diagnostic approaches such as watchful waiting for induction of amenorrhea 6 months after initiation of testosterone, observing for a withdrawal bleed after a progestin challenge, or use of a transabdominal approach to ultrasonography should all be considered. Persistent menses despite testosterone may also be related to body habitus; those with higher levels of body adipose tissue have higher endogenous estrogen levels and increased conversion of testosterone to estradiol through the peripheral aromatization process.
Therapeutic approaches based on etiology
Increasing the dosage and frequency of dosing (1 and 2 weeks) of intramuscular testosterone has been found to be positively correlated with rapidity of amenorrhea induction. The time to cessation of menses has been reported as ranging from 1-13 months [27-31] and in addition to individual genetic and physiologic factors may very well depend on the formulation or route of testosterone administration.
Physiologically, amenorrhea induction rates should correlate to increased testosterone levels (to physiologic male range) as well as possible decreased estrogen levels seen with androgen therapy, however many will achieve amenorrhea despite elevated estrogen levels and sub-physiologic male testosterone levels. For example, one study of transgender men presenting for initiation of cross-sex hormones found that 84% of those completing the study were amenorrheic at 6 months. This was despite many only 58% achieving physiologic male total testosterone levels and 68% achieving physiologic male free testosterone levels. However in the setting of persistent menses, adjustment of hormone regimen and dosing may be appropriate. The addition of an oral, injected, implanted, or intrauterine (IUD) progestogen may serve as an adjunct to induction of amenorrhea. Endometrial ablation can be considered  for those transgender men who do not desire future fertility and who also either decline hysterectomy or have surgical complications. The levonorgestrel intrauterine system (IUS/IUD), which in non-transgender women can either significantly decrease menstrual flow or fully induce amenorrhea, has the added contraceptive benefit for those at risk since some may still ovulate despite male physiologic testosterone levels.
Aromatase inhibitors (AIs) such as anastrazole or letrozole may be considered as short-term adjunctive therapy in achieving amenorrhea for those with persistent menses on testosterone. Aromatase is expressed throughout the body including the ovaries, endometrium, skin, bone, breast, brain and adipose tissue. AIs have been used for the treatment of estrogen receptor positive breast cancer, endometriosis, and ovulation induction. AIs have also been shown to reduce vaginal bleeding and pelvic pain in combination with other hormone therapies such as progestins or combined oral contraceptives.[33-35] In non-transgender women, treatment with AIs without add-back estrogen therapy has led to symptoms of medical menopause: hot-flashes, arthralgias, mood disturbances, fatigue, vaginal dryness, decreased bone mineral density, and fractures. In transgender men concurrently using testosterone, these symptoms may be attenuated or even absent.
What remains unclear is the AI dose necessary in the setting of male-range testosterone levels in comparison with the roughly 10-fold lower physiological female estrogen levels released by the ovaries. Since AIs have been used for ovulation induction, contraception should be considered in transgender men who may be at risk for pregnancy. Weight loss plays a critical role in all cases for health promotion as well as resulting in amenorrhea through reduction of adipose containing aromatase.
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