A mouse model to investigate the impact of testosterone therapy on reproduction in transgender men.

STUDY QUESTION: Can mice serve as a translational model to investigate the reproductive effects of testosterone (T) therapy commonly used by transgender men? SUMMARY ANSWER: T enanthate subcutaneous injections at 0.45 mg twice weekly can be used in the postpubertal C57BL/6N female mouse to investigate the reproductive effects of T therapy given to transgender men. WHAT IS KNOWN ALREADY: Most models of T treatment in female mice involve prenatal or prepubertal administration, which are not applicable to transgender men who often begin T therapy after puberty. Studies that have looked at the impact of postpubertal T treatment in female mice have generally not investigated reproductive outcomes. STUDY DESIGN, SIZE, DURATION: A total of 20 C57BL/6N female mice were used for this study. Study groups (n = 5 mice per group) included sesame oil vehicle controls and three doses of T enanthate (0.225, 0.45 and 0.90 mg). Mice were injected subcutaneously twice weekly for 6 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: Daily vaginal cytology was performed prior to initiation of treatment to confirm that all mice were cycling. At 8-9 weeks of age, therapy with subcutaneous T enanthate (0.225, 0.45 or 0.90 mg) or the vehicle control was begun. T therapy continued for 6 weeks, at which point mice were sacrificed and compared to control mice sacrificed during diestrus/metestrus. Data collected included daily vaginal cytology, weekly and terminal reproductive hormone levels, terminal body/organ weights/measurements, ovarian follicular distribution/morphology and corpora lutea counts. MAIN RESULTS AND THE ROLE OF CHANCE: Of the mice treated with 0.90 mg T enanthate, two of five mice experienced vaginal prolapse, so this group was excluded from further analysis. T enanthate administration twice weekly at 0.225 or 0.45 mg resulted in cessation of cyclicity and persistent diestrus. One of five mice at the 0.225-mg dose resumed cycling after 2.5 weeks of T therapy. As compared to controls, T-treated mice had sustained elevated T levels and luteinizing hormone (LH) suppression in the terminal blood sample. T-treated mice demonstrated increases in clitoral area and atretic cyst-like late antral follicles (0.45 mg only) as compared to controls. No reduction in primordial, primary, secondary or total antral follicle counts was detected in T-treated mice as compared to controls, and T-treated mice demonstrated an absence of corpora lutea. LIMITATIONS, REASONS FOR CAUTION: Mouse models can provide us with relevant key findings for further exploration but may not perfectly mirror human reproductive physiology. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this report describes the first mouse model mimicking T therapy given to transgender men that facilitates analysis of reproductive changes. This model allows for future studies comparing duration and reversibility of T-induced changes, on the reproductive and other systems. It supports a role for T therapy in suppressing the hypothalamic-pituitary-gonadal axis in adult female mice as evidenced by LH suppression, persistent diestrus and absence of corpora lutea. The increase in atretic cyst-like late antral follicles aligns with the increased prevalence of polycystic ovary morphology seen in case series of transgender men treated with T therapy. The results also suggest that T therapy does not deplete the ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the American Society for Reproductive Medicine/Society of Reproductive Endocrinology and Infertility Grant and NIH R01-HD098233 to M.B.M. and University of Michigan Office of Research funding (U058227). H.M.K. was supported by the Career Training in Reproductive Biology and Medical Scientist Training Program T32 NIH Training Grants (T32-HD079342, T32-GM07863) as well as the Cellular and Molecular Biology Program. The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by the Eunice Kennedy Shriver NICHD/NIH (NCTRI) Grant P50-HD28934. E.E.M. consults for Allergan. No other authors have competing interests.

Establishing a population-based patient-reported outcomes study (PROMs) using national cancer registries across two jurisdictions: the Prostate Cancer Treatment, your experience (PiCTure) study.

OBJECTIVE: To establish an international patient-reported outcomes (PROMs) study among prostate cancer survivors, up to 18 years postdiagnosis, in two countries with different healthcare systems and ethical frameworks. DESIGN: A cross-sectional, postal survey of prostate cancer survivors sampled and recruited via two population-based cancer registries. Healthcare professionals (HCPs) evaluated patients for eligibility to participate. Questionnaires contained validated instruments to assess health-related quality of life and psychological well-being, including QLQ-C30, QLQ-PR25, EQ-5D-5L, 21-question Depression, Anxiety and Stress Scale (DASS-21) and the Decisional Regret Scale. SETTING: Republic of Ireland (RoI) and Northern Ireland (NI). PRIMARY OUTCOME MEASURES: Registration completeness, predictors of eligibility and response, data missingness, unweighted and weighted PROMs. RESULTS: Prostate cancer registration was 80% (95% CI 75% to 84%) and 91% (95% CI 89% to 93%) complete 2 years postdiagnosis in NI and RoI, respectively. Of 12,322 survivors sampled from registries, 53% (n=6559) were classified as eligible following HCP screening. In the multivariate analysis, significant predictors of eligibility were: being ≤59 years of age at diagnosis (p<0.001), short-term survivor (<5 years postdiagnosis; p<0.001) and from RoI (p<0.001). 3348 completed the questionnaire, yielding a 54% adjusted response rate. 13% of men or their families called the study freephone with queries for assistance with questionnaire completion or to talk about their experience. Significant predictors of response in multivariate analysis were: being ≤59 years at diagnosis (p<0.001) and from RoI (p=0.016). Mean number of missing questions in validated instruments ranged from 0.12 (SD 0.71; EQ-5D-5L) to 3.72 (SD 6.30; QLQ-PR25). Weighted and unweighted mean EQ-5D-5L, QLQ-C30 and QLQ-PR25 scores were similar, as were the weighted and unweighted prevalences of depression, anxiety and distress. CONCLUSIONS: It was feasible to perform PROMs studies across jurisdictions, using cancer registries as sampling frames; we amassed one of the largest, international, population-based data set of prostate cancer survivors. We highlight improvements which could inform future PROMs studies, including utilising general practitioners to assess eligibility and providing a freephone service.

Do women who intermittently attend breast screening differ from those who attend every invitation and those who never attend?

OBJECTIVES: Analysis of screening uptake usually dichotomizes women into attenders and non-attenders, though many women respond positively to some but not all invitations. This paper studies these intermittent attenders. METHODS: A cohort of 8,571 women invited for consecutive breast screens in the Northern Ireland Breast Screening Programme were followed in a study linking screening and census records. Multivariate logistic analysis was used to analyze the characteristics of those who attended both times (consistent), once (intermittent or 'one-time only'), or not at all (non-attenders). RESULTS: Overall, 15.5% of women attended once and 13.4% were non-attenders. Non-attenders were characteristically disadvantaged (as measured by social renting, car access, and employment status), less likely to be married, and more likely to be healthy. One-time attenders were younger, and suffering poor health, though there was no association with either social renting or employment status. Privately rented accommodation and city living was associated with both one-time attendance and non-attendance. CONCLUSIONS: One-time attenders are an important and distinct subgroup of screening invitees in this analysis. Their distinct characteristics suggest that transitory factors, such as change in marital status, ill-health, or addressing difficulties through change of residence are important. These distinct characteristics suggest the need for different approaches to increase attendance, among both intermittent attenders and those not attending at all.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland.

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent.

The low uptake of breast screening in cities is a major public health issue and may be due to organisational factors: a Census-based record linkage study.

BACKGROUND: Cancer screening uptake is generally lower in UK cities but quantifying city-level effects from causes due to population composition that comprise cities is hampered by data limitations. METHODS: A unique data linkage project combining a 2001 Census-based longitudinal study in Northern Ireland with the NHS Breast Screening Program. Validated uptake in the three years following the Census for Belfast Metropolitan Urban Area was compared against the rest of the country with adjustment for cohort attributes defined at Census. RESULTS: Belfast Metropolitan Urban Area contained 34.8% of invited women but a greater proportion who rented their accommodation (40.3%) or who did not have a car (47.1%). After full adjustment for demographic and socio-economic factors, Belfast Metropolitan Urban Area uptake was lower for first and subsequent screen (Odds ratio (OR) 0.72; 95% CIs 0.66, 0.78 and OR 0.58; 95% CIs 0.55, 0.62 respectively). There were no significant interactions between patient characteristics and area of residence indicating that all residents in Belfast Metropolitan Urban Area are equally affected. CONCLUSION: The reduced uptake of screening in cities is a major public health issue; the effects are large and a large proportion of the population are affected, organisational factors appear to be the primary cause. Strategies to correct this imbalance might help reduce inequalities in health.