Le gonadotropine umane disponibili: caratteristiche, efficacia e sicurezza

[Autom. eng. transl.] Gonadotropin therapy, based on drugs based on pituitary hormones, has been used effectively in men and women for the treatment of gonadotropin deficiency with various aetiology, using regimens based on urinary derivatives or on recombinants. The first generation of gonadotropins produced was menotropin (human Menopausal Gonadotropin, hMG), such as Meropur® and Menogon®, in which the follicle stimulating hormone (FSH) content is equal to that of luteinizing hormone (LH). Over time, increasingly purified gonadotropins of the LH content have been gradually introduced to the market: the most recent are represented by highly purified human urinary FSH (FSH-HP), such as Fostimon®, and by recombinant FSH (rFSH), such as Gonal F® and Puregon®. The indications of products of human derivation, as well as of recombinant ones, are similar: in women they can be used in case of anovulation (including women with polycystic ovary syndrome, PCOS) or of controlled hyperstimulation of the ovaries in women undergoing techniques assisted reproduction; in humans they only include the induction of spermatogenesis in patients with hypogonadotropic hypogonadism. The dosage varies depending on the drug and the clinical condition of the patient: to optimize its efficacy and safety, the rFSHs must however be administered at a lower total dosage and for a shorter treatment period than that generally used for Urinary FSH. The most recent evidence concerning the efficacy aspects in the comparison between FSH-HP (Fostimon) and its main competitors (the hMG Menopur and the rFSH Gonal F and Puregon) in women derive from the meta-analysis of Al-Inany et al., From the review Cochrane by van Wely et al. and from the meta-analysis by Matorras et al. Regarding efficacy, for the main outcomes of all three studies (live birth rate - LBR, advanced pregnancy rate - OPR and OPR / LBR ratio for women in the meta-analysis of Al-Inany et al., Live births or pregnancies advanced and clinically established pregnancies in that of van Wely et al., percentage of pregnancies per treatment cycle, per treated woman and at the first course of treatment in that of Matorras et al.) no statistically significant differences emerged between the two groups of treatment. The only exception, although slightly above the limit of statistical significance, was the result of Matoras et al. in relation to the percentage of pregnancies per treatment cycle in the subgroup of women treated with FSHHP and rFSH at the same dosage, which was 39% higher for the group treated with rFSH [Relative Risk (RR) = 1.39 with Confidence Interval 95% (95% CI): 1.004–1.936]. The efficacy of FSH for use in humans was instead evaluated in the Cochrane review by Attia et al .: it emerged that this treatment allows a significantly higher randomized pregnancy rate to be obtained compared to placebo or no therapy ( OR = 1.8; IC95% 1.03-3.17), also in the follow-up up to 3 months (OR = 1.92; IC95% 1.15-3.20) and in spontaneously obtained pregnancy rates (OR = 3.99, IC95% 1.80-8.82). In relation to safety, there were no significant differences between hMG, FSHHP and rFSH in the rate of multiple pregnancies, in the frequency of ovarian hyperstimulation syndrome (Ovarian Hyperstimulation Syndrome - OHSS), in the rate of treatment interruption (cancellation rate) or in the miscarriage rates. Finally, with regard to the hypothesis of transmission of prions, clinical practice and epidemiological evidence, as also emphasized by important European and American experts in the field, show that to date there are no data to support the