This was confirmed by another meta-analysis involving 945 286 patients in 8 retrospective cohort studies, most in the US.In 2012, the U.S. Justice Department announced GlaxoSmithKline had agreed to plead guilty and pay a $3 billion fine, in part for withholding the results of two studies of the cardiovascular safety of Avandia between 2001 and 2007. Death
There was no difference in all cause and vascular death in a meta-analysis of 4 trials against controls. Two meta-analyses of cohort studies found excess deaths against pioglitazone. Stroke
An retrospective observational study performed using Medicare data found that patients treated with rosiglitazone had a 27% higher risk of stroke compared to those treated with pioglitazone. Bone fractures
GlaxoSmithKline reported a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide. The information was based on data from the ADOPT trial The same increase has been found with pioglitazone (Actos), another thiazolidinedione. A meta-analysis of 10 RCTs, involving 13,715 patients and including both rosiglitazone- and pioglitazone-treated patients, showed an overall 45% increased risk of fracture with thiazolidone use compared with placebo or active comparator. It doubled the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes. Hypoglycaemia
The risk of hypoglycaemia is reduced with thiazolidinediones when compared with sulfonylureas; the risk is similar to the risk with metformin (high strength of evidence).
The term hypogonadism usually means permanent rather than transient or reversible defects, and usually implies deficiency of reproductive hormones, with or without fertility defects. The term is less commonly used for infertility without hormone deficiency. There are many possible types of hypogonadism and several ways to categorize them. Hypogonadism is also categorized by endocrinologists by the level of the reproductive system that is defective. Physicians measure gonadotropins (LH and FSH) to distinguish primary from secondary hypogonadism. In primary hypogonadism the LH and/or FSH are usually elevated, meaning the problem is in the testicles (hyper-gonatropic hypogonadism); whereas in secondary hypogonadism, both are normal or low, suggesting the problem is in the brain (hypo-gonatropic hypogonadism). Affected system
Hypogonadism resulting from defects of the gonads is referred to as hypergonadotropic hypogonadism or primary hypogonadism. Examples include Klinefelter syndrome and Turner syndrome. Mumps is known to cause testicular failure, and in recent years has been immunized against in the US. A varicocele can reduce hormonal production as well. Hypogonadism resulting from hypothalamic or pituitary defects is termed hypogonadotropic hypogonadism (HH), secondary hypogonadism, or central hypogonadism (referring to the central nervous system).Examples of hypothalamic defects include Kallmann syndrome. Examples of pituitary defects include hypopituitarism and pituitary hypoplasia. An example of a hypogonadism resulting from the lack of hormone response is androgen insensitivity syndrome, where there are inadequate receptors to bind the testosterone, resulting in varying clinical phenotypes of sexual characteristics despite XY chromosomes.