Sex reassignment therapy
Sex reassignment therapy (SRT) is an umbrella term for all medical treatments related to sex reassignment of both transgender and intersex people. Sex reassignment surgery (such as orchiectomy) alters primary sex characteristics, including chest surgery such as top surgery or breast augmentation, or, in the case of trans women, a trachea shave, facial feminization surgery or permanent hair removal. To obtain sex reassignment therapy, transsexual people are generally required to undergo a psychological evaluation and receive a diagnosis of gender identity disorder in accordance with the Standards of Care (SOC) as published by the World Professional Association for Transgender Health. This assessment is usually accompanied by counseling on issues of adjustment to the desired gender role, effects and risks of medical treatments, and sometimes also by psychological therapy. The SOC are intended as guidelines, not inflexible rules, and are intended to ensure that clients are properly informed and in sound psychological health, and to discourage people from transitioning based on unrealistic expectations. Gender roles and transitioning
After an initial psychological evaluation, trans men and trans women may begin medical treatment, starting with hormone replacement therapy or hormone blockers. In these cases, people who change their gender are usually required to live as members of their target gender for at least one year prior to genital surgery, gaining real-life experience, which is sometimes called the "real-life test" (RLT). Transsexual individuals may undergo some, all, or none of the medical procedures available, depending on personal feelings, health, income, and other considerations.
However, MRP2 is also the preferential route of export for certain sulfated conjugated BAs (taurolithocholic acid and glycolithocholic acid), so its inhibition could contribute to cholestasis.On the hepatocyte basolateral membrane, Na+-taurocholate cotransporting peptide (NTCP) is the major transporter of conjugated bile acids. Enterohepatic bile flow requires the concerted activity of both NTCP and BSEP, which form the major route by which BAs enter and exit hepatocytes respectively. Therefore, NTCP inhibitors, such as cyclosporine A, ketoconazole, propranolol, furosemide, rifamycin, saquinavir, and ritonavir, should theoretically cause cholestasis by decreasing hepatocyte BA uptake. However, no relationship was found between NTCP inhibition and DIC risk, possibly because basolateral sodium-independent OATPs can partially compensate for bile salt uptake. Therefore, NTCP inhibition alone seems to be insufficient for causeing cholestasis. Indeed, the cholestatic effect of cyclosporine A relies on its inhibition of both NTCP and the compensatory OATP1B1.In addition to direct inhibition, drugs can also induce cholestasis by promoting downregulation and internalization of transporters. For example, cyclosporine A in rats was shown to induce BSEP internalization in addition to inhibition. Furthermore, human hepatocytes showed decreased expression of BSEP mRNA and protein following long-term exposure to metformin and tamoxifen, neither of which are direct BSEP inhibitors.Bile canaliculi dynamics refers to the contractile motion of bile canaliculi (ducts) required for bile flow. Cholestasis can result when drugs constrict or dilate bile canaliculi. Constrictors include chlorpromazine, nefazodone, troglitazone, perhexiline, metformin, cyclosporin A.