Clinical studies have consistently associated medical and recreational opioid use with hypogonadism (low sex hormone levels) in different sexes. The effect is dose-dependent. Most studies suggest that the majority (perhaps as much as 90%) of chronic opioid users suffer from hypogonadism. Opioids can also interfere with menstruation in women by limiting the production of luteinizing hormone (LH). Opioid-induced hypogonadism likely causes the strong association of opioid use with osteoporosis and bone fracture, due to deficiency in estradiol. It also may increase pain and thereby interfere with the intended clinical effect of opioid treatment. Opioid-induced hypogonadism is likely caused by their agonism of opioid receptors in the hypothalamus and the pituitary gland. One study found that the depressed testosterone levels of heroin addicts returned to normal within one month of abstinence, suggesting that the effect is readily reversible and is not permanent. , the effect of low-dose or acute opioid use on the endocrine system is unclear. Long-term use of opioids can affect the other hormonal systems as well.