The five observational studies and the Xu meta-analysis were discussed at a joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on September 17, 2014. Based on these findings, the advisory committee members were in general agreement that the signal of cardiovascular risk is weak and that only a prospective, well-controlled clinical trial could determine whether testosterone causes cardiovascular harm. The Corona study was recently published and could not be reviewed in time to be presented at the Advisory Committee meeting; however, we have reviewed the study and factored its findings into our overall assessment.
Kim et al. (2008) analyzed the CHD7 gene in 197 patients with Kallmann syndrome or normosmic hypogonadotropic hypogonadism and identified 7 different heterozygous mutations in 7 sporadic patients, 3 with KS and 4 with IHH, respectively (see, ., -). A splice site mutation () in a female KS patient with cleft lip and palate and hearing loss had previously been reported by Jongmans et al. (2008) in 2 brothers with 'relatively mild' CHARGE syndrome (214800), and a missense mutation () that was found in a male patient with IHH, cleft lip, and cryptorchidism had previously been reported by Delahaye et al. (2007) in a mother and 2 sons from a family with both typical and atypical CHARGE syndrome phenotypes. Kim et al. (2008) concluded that both normosmic IHH and Kallmann syndrome due to CHD7 mutations are mild allelic variants of CHARGE syndrome.