Sex Proportionality in Pre-clinical and Clinical Trials: An Evaluation of 22 Marketing Authorization Application Dossiers Submitted to the European Medicines Agency

This study assessed to what extent women were included in all phases of drug development; whether the clinical studies in the marketing authorization application dossiers include information per sex; and explored whether there are differences between women and men in the drugs' efficacy and safety. Data were extracted from dossiers submitted to the European Medicines Agency. Twenty-two dossiers of drugs approved between 2011 and 2015 for the treatment of various diseases were included. Female animals were included in only 9% of the pharmacodynamics studies, but female and male animals were included in all toxicology studies. Although fewer women than men were included in the clinical studies used to evaluate pharmacokinetics (PK) (29 to 40% women), all dossiers contained sex-specific PK parameter estimations. In the phase III trials, inclusion of women was proportional to disease prevalence for depression, epilepsy, thrombosis, and diabetes [participation to prevalence ratio (PPR) range: 0.91–1.04], but women were considered underrepresented for schizophrenia, hepatitis C, hypercholesterolemia, HIV, and heart failure (PPR range: 0.49-0.74). All dossiers contained sex-specific subgroup analyses of efficacy and safety. There seemed to be higher efficacy for women in one dossier and a trend toward lower efficacy in another dossier. More women had adverse events in both treatment (73.0 vs. 70.6%, p < 0.001) and placebo groups (69.5 vs. 65.5%, p < 0.001). In conclusion, women were included throughout all phases of clinical drug research, and sex-specific information was available in the evaluated dossiers. The included number of women was, however, not always proportional to disease prevalence rates

Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People-Results from the European Network for the Investigation of Gender Incongruence

Introduction: Although many studies on the short- and long-term effects of hormonal treatment (HT) in trans people focus on objective changes such as body composition or bone density, few studies have evaluated self-reported effects of HT. Aim: To evaluate self-reported symptoms during the first year of HT in trans people. Methods: This study is part of the European Network for the Investigation of Gender Incongruence, a multicenter prospective cohort study. For this study, 205 trans women and 193 trans men from the gender clinics of Amsterdam, Ghent, and Florence, who were >18 years of age and started hormonal treatment were included. Questionnaires, self-developed based on the Menopause Rating scale and clinical experiences, were completed, and changes in symptom scores were analyzed using linear mixed models. Main Outcome Measures: Self-reported psycho vegetative symptoms, as well as physical, cognitive, emotional, sexual and genital complaints, and pain were evaluated at baseline and after 3, 6, and 12 months of HT using a 4-point Likert scale (no, mild, moderate, or severe complaints). Results: In trans men, with a median age of 23, transient increases were reported in night sweats, weight gain, and clitoral pain. Persistent increases were reported for hot flashes, balding, voice instability, acne, and increase in sexual desire, whereas emotional instability, fear, and menses decreased. For trans women, with a median age of 29, hot flashes, night sweats, fatigue, weight gain, changes in olfactory sense, brittle nails, emotional instability, mood swings, and breast tenderness increased persistently during 12 months of HT, whereas a decrease was observed for balding and sexual desire. Sleeping difficulties decreased temporarily. No changes were observed in palpitations, dizziness, abdominal complaints, anxiety, panic attacks, cognition, and pain, except for clitoral and breast pain. Clinical Implications: Knowledge on the occurrence of these self-reported, subjective effects and their course over time may help physicians informing trans people starting with and during HT. Strengths & Limitations: This study was performed in a large cohort of trans people. The follow-up period was limited to 12 months. Conclusion: Changes in self-reported symptoms were mentioned in all investigated areas, except cognition. Most symptoms were as expected and even desired, whereas others may be considered unpleasant by some trans people. van Dijk D, Dekker MJHJ, Conemans EB, et al. Explorative Prospective Evaluation of Short-Term Subjective Effects of Hormonal Treatment in Trans People—Results from the European Network for the Investigation of Gender Incongruence. J Sex Med 2019;16:1297–1309