Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia

Abstract

Background: Depending on CYP21A2 genotype, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to biochemical alterations (including hyperandrogenism, hypocortisolism, and hypoaldosteronism) and a wide spectrum of phenotypic disease manifestation. The latter include life-threatening salt-wasting crises, prenatal virilization of genitalia in women (classic CAH [C-CAH]) as well as milder forms of the disease exclusively presenting with hirsutism, acne or reduced fertility (nonclassic CAH [NC-CAH]), and could influence sexual function and identity. Aim: The present study evaluated sexual function, gender identification, and partner preference in women with C-CAH and NC-CAH. Methods: In a cross-sectional cohort analysis, 35 female patients with CAH were divided into 2 groups: C-CAH (salt-wasting/simple virilizing; n ¼ 17) and NC-CAH (n ¼ 18) according to genotype and phenotype. Sexual function and sexual distress were assessed using established questionnaires, including the Female Sexual Function Index. Phenotype (defined by signs of hyperandrogenism) was assessed clinically (Ferriman-Gallwey score) and with the ovulatory function index. CYP21A2 genotype was determined by Sanger sequencing and multiplex ligation-dependent probe amplification. Sexual function was also separately analyzed in the context of clinical signs of androgenization in women with (n ¼ 13) and without acne (n ¼ 22). Outcomes: The study outcomes were sexual function and sexual distress in relation to genotype, clinical signs of androgenization, and biochemical parameters. Results: Women with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress, as well as biochemical evidence of hyperandrogenism (higher dehydroepiandrosterone sulfate and lower SHBG) and a trend toward more clinical signs of hyperandrogenism (hirsutism). Indicators of in utero and childhood androgen excess as well as the presence of acne in all patients were related to lower sexual function and higher sexual distress. Clinical signs of hyperandrogenism correlated well with cardiovascular and metabolic risk factors. Clinical Translation: Women with NC-CAH and women with clinical signs of hyperandrogenism demonstrated higher distress compared to women with C-CAH and women without clinical signs of hyperandrogenism, respectively, regarding different aspects of sexual function. Conclusions: These data underline the importance of early diagnosis and therapy initiation, especially in patients with NC-CAH.

Anti-androgenic therapy in young patients and its impact on intensity of hirsutism, acne, menstrual pain intensity and sexuality — a preliminary study

“…That is probably because of the aesthetic improvement obtained by the pill intake. More researches are needed to be done to find out if other groups of antiandrogenic pills have similar impact on women's sexual behavior [21,22].…”

“…One of the studies analyzed the influence of genotype and hyperandrogenism on sexual function, gender identification, and partner preference in women with congenital adrenal hyperplasia (CAH) who present symptoms of hyperandrogenism [23]. This study is pointing to importance of early beginning of antiandrogenic treatment in women with congenital adrenal hyperplasia [23].…”

Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…Other studies show higher but still low-fertility rate since it has been established that elevated circulating adrenal androgens and elevated serum progesterone concentrations may hinder ovulation and embrio implantation [139][140][141]. However, all agree that some additional factors contribute to the low reproductive rate such as the decreased sexual activity, higher sexual distress, higher prevalence of homosexuality or bisexuality, and unwillingness to pursue motherhood [136,[142][143][144][145]. Due to individualized fertility therapy, newer studies show much higher pregnancy rates in women with CAH approaching the fertility rate in the general population [81,140].…”

Individualized care for patients with intersex (differences of sex development): part 4/5.Considering the Ifs, Whens, and Whats regarding sexual-reproductive system surgery

“…A cross-sectional cohort analysis illustrates the multiple factors involved in sexual function outcomes by those who had normal genitalia (non-classical individuals). This group plus others with clinical signs of hyperandrogenism had higher distress regarding sexual function compared to women without clinical signs of hyperandrogenism, highlighting the importance of early diagnosis and therapy initiation in all patients with CAH including those with non-classical CAH [35,36]. How efficacious surgical external genital construction is in overall good quality of life depends not only the quality of surgery but other factors, some of which are alluded to above.…”