1/11/2024 0 Comments Sexy moods![]() ![]() Recent research suggests that men are potentially underdiagnosed with major depressive disorder (MDD) due to sex differences in symptoms 20. Women experience their first episode of depression earlier than men and have more cumulative episodes over their lifespan 19. The rates are higher when comorbid depression with anxiety or atypical/somatic presentation of depression is considered 18. ![]() Women have twice the risk of developing depression and anxiety disorders compared with men 17. This is particularly problematic as the transgender and intersex populations have a high rate of depression, self-harm and suicidal ideation 16.Įxamination of cisgender individuals has identified differences in the epidemiology, symptoms and onset of mood disorders. However, this leaves a growing part of the population who are transgender or intersex unaccounted for. In addition, studies that use SABV focus on genetic/hormonal sex of the subject. As such, it is impossible to identify gender differences for preclinical studies performed in non-humans. SABV differs from gender, which is a multifaceted societal, social and self-construct 15. In part because of these drug recalls, in 2016 the National Institutes of Health (NIH) mandated that researchers consider sex as a biological variable (SABV) in their preclinical research to obtain funding 14. This study identified that eight (Pondimin, Redux, Seldane, Posicor, Hismanal, Rezulin, Propulsid and Lotronex) out of ten of the drugs posed greater risks of adverse events to women than to men 13. This issue first garnered public attention when drugs pulled off the market by the Food and Drug Administration from 1997 to 2001 were analyzed to determine the level of risk they posed to women. Clinical trials that tested the drug exclusively in men or skewed male in their number of participants were more successful 11, 12, demonstrating the lack of generalizability of male-exclusive preclinical trials to sex-inclusive clinical trials. Most notably is the case of corticotrophin-releasing factor (CRF) inhibitors, which had dramatic effects in preclinical trials using only male subjects 8 and then failed when tested in combined groups of men and women 9, 10. For many conditions, including mood disorders, which are more common in women, this sole use of male animals for a drug development pipeline produced a striking mismatch for the efficacy of therapeutic treatments when they were subsequently tested using women participants. Testosterone and corticosterone levels are diurnal 7, and there are individual differences across all types of steroid hormones. Furthermore, the concept that male rodents do not have hormonal cycles is erroneous. Recent research has tested the amount of variability across the cycle compared with males and found it non-significant and negligible 6. Researchers avoided female subjects because they believed females introduce too much variability due to their estrous cycle and the accompanying changes in hormone levels. ![]()
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