Abstract Introduction Anorgasmia may be conceptualized as an extreme variant of delayed ejaculation (DE) in which orgasm cannot be achieved. Anorgasmia may be divided into three categories: primary complete (has never had a normal orgasm), primary incomplete (lifelong undue delay in reaching a climax during sexual activity) or secondary (men who had normal orgasms before but then develop a failure to achieve it). Objective This systematic review aimed to determine the effectiveness and safety of pharmacological therapy in men older than 18 years with primary or secondary anorgasmia in terms of induced orgasm, improvement of International Index of Erectile Function (IIEF) or Arizona Sexual Experience Scale (ASEX). Methods We included men older than 18 years with primary or secondary anorgasmia with any comorbidity or concomitant medication use. The primary outcome was induced orgasm, change in IIEF or ASEX, and safety. We designed a search strategy in MEDLINE (OVID), EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. Two researchers reviewed each reference by title and abstract. Then, reviewers confirmed all data in full texts of relevant studies, applied pre-specified inclusion and exclusion criteria and extracted the data. We assessed the risk of bias based on the STROBE statement for observational studies and the Rob 2.0 tool for clinical trials. Results We included 234 patients with anorgasmia (primary or secondary), and 231 patients were treated with pharmacological therapy in the seven included studies. Three studies were observational and four were clinical trials. Some pathologies reported were history of prostatectomy, hypogonadism, psychiatric disorders such as dysthymia, anxiety or depression, and use of antidepressants. Cabergoline was the most frequently administered treatment, followed by yohimbine and bupropion. To a lesser extent they were treated with pycnogenol, cyproheptadine and amantadine. The cabergoline improved orgasm in 66% of the population included by Hollander AB, 2016, the duration of therapy was also the longest at 9.8 months (5.4-13.5). Another study with cabergoline showed a change in IIEF orgasmic function in the intervention group of 3.6 points versus the control of 1.8 (P = <0.001). Adeniyi AA, 2007 and Keller Ashton A, 1997 showed significant improvement in orgasm with yohimbine. The IIEF improved significantly in Abdel-Hamid IA, 2011 with the use of daily bupropion. The ASEX improved with pycnogenol and was maintained in months 2,3 and 4 (p ≤ 0.05) in Smetanka A, 2019. Cyproheptadine before sexual activity had an improvement in orgasm in up to 50% of patients in the studies by Keller Ashton A, 1997 and Hsu JH, 1995. The side effects presented are all mild (headache, nausea, insomnia or sweating) reported in three studies. Amantadine required discontinuation due to symptoms of depression, which improved 48 hours after discontinuation. Conclusions Cabergoline, yohimbine, bupropion and pignogenol may have a positive effect on orgasmic function in patients with primary or secondary anorgasmia, even in those not taking antidepressants. Cyproheptadine before sexual activity improves orgasm in half of patients, however, with few cases described until then. All medications are very well tolerated, with some mild side effects. Disclosure No.
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