Gender-affirming hormone therapy (GAHT) is increasingly prescribed to transgender men and gender diverse individuals to better align their affirmed gender identity and somatic phenotype, aiming to improve psychosocial well-being. However, the long-term outcomes of GAHT, especially risk of hormone-related malignancy, remains unclear. We report a case of transgender man on long-term GAHT with testosterone who developed recurrent hormone-sensitive endometrioid ovarian cancer. Treatment with medroxyprogesterone acetate effectively suppressed serum estradiol (measured by liquid chromatography-mass spectrometry) but resulted in intolerable physical and mental health symptoms from hypogonadism. The nonaromatizable androgen 19-nortestosterone (nandrolone) was initiated as an alternative and successfully improved quality of life while maintaining bone and muscle health. This case underscores the importance of coordinated care within a multidisciplinary team.

Transgender and gender diverse (TGD) individuals seeking gender affirming treatment are an increasing demographic in today's society; such treatments include hormonal and surgical interventions aimed at alleviating gender dysphoria and increasing quality of life. A number of diagnostic pathology tests are provided to medical professionals with sex specific reference intervals (RIs) for interpretation, due to sex specific physiological differences, organ size and hormone levels for example. These tests may be reported with RIs that are not appropriate, and interpretation for the medical professional can be challenging. From the laboratory perspective, there are limitations in Laboratory Information Management Systems (LIMS) and the ability of these databases to record both sex and gender identifiers, as well as the reporting of appropriate RIs. The use of RIs derived from the transgender population is complex, studies generally have a low sample size and include adults with long established hormonal treatments. The age of an individual undergoing gender affirming therapy has decreased, and the use of Gonadotrophin Releasing Hormone analogues adds complexity. In this review, we will discuss the current challenges and perspectives regarding the reporting of reference intervals in the TGD population, the derivation of personalized or transgender specific RIs and interpretation of specific diagnostic tests.

Transgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals. There are no clinical guidelines specific for TGD individuals with LS, highlighting a need to improve the quality of care for this population. There is an urgent need for cancer surveillance recommendations for TGD patients. This commentary provides recommendations for cancer surveillance, risk-reducing strategies, and genetic counseling considerations for TGD patients with LS.

Literature focused on cancer screening and management is lacking in the transgender population.

To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming (TGNC) patients.

We performed a systematic search of PubMed on January 5th, 2022, with the following terms: "TGNC", OR "transgender", OR "gender non-conforming", OR "gender nonbinary" AND "cancer screening", AND "breast cancer", AND "cervical cancer", AND "uterine cancer", AND "ovarian cancer", AND "prostate cancer", AND "testicular cancer", AND "surveillance", AND "follow-up", AND "management". 70 unique publications were used. The findings are discussed under "Screening" and "Management" categories.

Screening: Current cancer screening recommendations default to cis-gender protocols. However, long-term gender-affirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection. The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer. Management: Prior to undergoing Gender Affirmation Surgery (GAS), discussion should address cancer screening and management in the organs remaining in situ. Cancer treatment in this population requires consideration for chemotherapy, radiation, surgery and/or reconstruction. Modification of hormone therapy is decided on a case-by-case basis. The use of prophylactic vs aesthetic techniques in surgery is still debated.

When assessing transgender individuals for GAS, a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential. Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social, medical, surgical and gender affirming surgery related specifications. Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes. A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS. Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address. We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature. Further research is required to ensure more comprehensive and individualized care for this population.

The transmasculine and gender diverse (TMGD) spectrum includes transgender men and non-binary individuals whose sex was assigned female at birth. Many TMGD patients pursue treatment with exogenous testosterone to acquire masculine characteristics. Some may choose to undergo gynecological gender-affirming surgery for total hysterectomy with bilateral salpingectomy and/or bilateral oophorectomy (TH/BSO). The decision to retain or remove the ovaries in the setting of chronic testosterone therapy has implications on reproductive health, oncologic risk, endocrine management, cardiovascular health, bone density and neurocognitive status. However, there is limited evidence on the long-term outcomes from this intervention.

Here we review health-related outcomes of oophorectomy in TMGD population treated with chronic testosterone therapy in order to guide clinicians and patients in the decision to retain or remove their ovaries.

We conducted a systematic literature review following PRISMA guidelines. MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane Library databases were searched for peer-reviewed studies published prior to October 26, 2021 that: (i) included transgender men/TMGD individuals in the study populations; (ii) were full-text randomized controlled studies, case reports, case series, retrospective cohort studies, prospective cohort studies, qualitative studies, and cross-sectional studies; and (iii) specifically discussed ovaries, hysterectomy, oophorectomy, ovariectomy, or gonadectomy.

We identified 469 studies, of which 39 met our inclusion criteria for this review. Three studies discussed fertility outcomes, 11 assessed histopathological changes to the ovaries, 6 discussed ovarian oncological outcomes, 8 addressed endocrine considerations, 3 discussed cardiovascular health outcomes, and 8 discussed bone density. No studies were found that examined surgical outcomes or neurocognitive changes.

There is little information to guide TMGD individuals who are considering TH/BSO versus TH/BS with ovarian retention. Our review suggests that there is limited evidence to suggest that fertility preservation is successful after TH/BS with ovarian retention. Current evidence does not support regular reduction in testosterone dosing following oophorectomy. Estradiol levels are likely higher in individuals that choose ovarian retention, but this has not been clearly demonstrated. Although bone mineral density decreases following oophorectomy, data demonstrating an increased fracture risk are lacking. No studies have described the specific impact on neurocognitive function, or changes in operative complications. Further research evaluating long-term health outcomes of oophorectomy for TMGD individuals treated with chronic testosterone therapy is warranted to provide comprehensive, evidence-based healthcare to this patient population. Sahil Kumar, Smita Mukherjee, Cormac O'Dwyer, et al. Health Outcomes Associated With Having an Oophorectomy Versus Retaining One's Ovaries for Transmasculine and Gender Diverse Individuals Treated With Testosterone Therapy: A Systematic Review. Sex Med Rev 2022;10:636-647.

The Every Woman StudyTM: Canadian Edition is the most comprehensive study to date exploring patient-reported experiences of ovarian cancer (OC) on a national scale. An online survey conducted in Fall 2020 included individuals diagnosed with OC in Canada, reporting responses from 557 women from 11 Canadian provinces/territories. Median age at diagnosis was 54 (11−80), 61% were diagnosed between 2016−2020, 59% were stage III/IV and all subtypes of OC were represented. Overall, 23% had a family history of OC, 75% had genetic testing and 19% reported having a BRCA1/2 mutation. Most (87%) had symptoms prior to diagnosis. A timely diagnosis of OC (≤3 months from first presentation with symptoms) was predicted by age (>50) or abdominal pain/persistent bloating as the primary symptom. Predictors of an acute diagnosis (<1 month) included region, ER/urgent care doctor as first healthcare provider or stage III/IV disease. Regional differences in genetic testing, treatments and clinical trial participation were also noted. Respondents cited substantial physical, emotional, practical and financial impacts of an OC diagnosis. Our national survey has revealed differences in the pathway to diagnosis and post-diagnostic care among Canadian women with OC, with region, initial healthcare provider, specific symptoms and age playing key roles. We have identified many opportunities to improve both clinical and supportive care of OC patients across the country.