Mineralocorticoid is only added in cases where the plasma renin activity is high. A third key aspect of management is suppression of central precocious puberty if it has begun. The usual clues to central puberty in boys are that the testes are pubertal in size, or that testosterone remains elevated even when the 17OHP has been reduced toward normal. In girls central puberty is less often a problem, but breast development would be the main clue. Central precocious puberty is suppressed when appropriate by leuprolide. As outlined above, recent additions to treatment to preserve growth include aromatase inhibition to slow bone maturation by reducing the amount of testosterone converted to estradiol, and use of blockers of estrogen for the same purpose. Once adrenal suppression has been achieved, the patient needs stress steroid coverage as described above for significant illness or injury. Other alleles result in even milder degrees of hyperandrogenism that may not even cause problems in males and may not be recognized until adolescence or later in females. Mild androgen effects in young women may include hirsutism, acne, or anovulation (which in turn can cause infertility). Testosterone levels in these women may be mildly elevated, or simply above average. These clinical features are those of polycystic ovary syndrome (PCOS), and a small percentage of women with PCOS are found to have late-onset CAH when investigated. Diagnosis of late-onset CAH may be suspected from a high 17α-hydroxyprogesterone level, but some cases are so mild that the elevation is only demonstrable after cosyntropin stimulation. Treatment may involve a combination of very low dose glucocorticoid to reduce adrenal androgen production and any of various agents to block the androgen effects and/or induce ovulation. It was characterized in 1979 by Dr. Maria New. Prevalence has been described as 1 in 100 in certain populations. Infertility observed in adult males with congenital adrenal hyperplasia (CAH) has been associated with testicular adrenal rest tumors (TART) that may originate during childhood. TART in prepubertal males with classic CAH could be found during childhood (20%). Martinez-Aguayo et al. reported differences in markers of gonadal function in a subgroup of patients, especially in those with inadequate control. The "CYP21A2" gene for the P450c21 enzyme (also known as 21-hydroxylase) is at 6p21.3, amid genes "HLA B" and "HLA DR" coding for the major human histocompatibility loci (HLA).