ABSTRACT: Abstract Background: Partial Androgen Insensitivity Syndrome (PAIS) (OMIM # 312300) is one of the causes of Disorders/Differences of Sex Development with 46,XY karyotype and normal or increased testosterone secretion that results in atypical genitalia. In general, it is caused by inactivating mutations on AR gene (Xq12 - OMIM * 313700), therefore it presents an X-linked recessive inheritance. Individuals raised as males have incomplete puberty with micropenis, sparse hairs, gynecomastia and increased LH, testosterone and estradiol serum levels. Therefore, the use of aromatase inhibitor in these cases becomes a logical indication aiming to increase testosterone levels in the tentative of supplanting its peripheral resistance and decreasing estrogen levels. Objective: To present clinical and laboratory data during the first year of use of aromatase inhibitor in puberty of three boys with confirmed molecular diagnosis of PAIS. Results: All subjects used letrozole (2.5 mg daily during 12 months). None reported significant side effects. Cases 1 and 2 are brothers (p.Ala596Tre). Case 1: Onset of treatment at age 12; height changed from 158 cm (z = +1.15) to 166 cm (z = +1.21), Tanner from G2P2T2 to G3P3T1, penis from 4.0 to 6.5 cm, LH from 7.5 to 18.3 IU/L (NR: 1.5 to 9.3 IU/L), testosterone from 361 to 1,347 ng/dL (NR: 165 to 763 ng/dL), estradiol from 35 to <5.0 pg/mL (NR: < 40 pg/mL) and bone age remained at 13 years. Case 2: Onset of treatment at age 11; height changed from 156 cm (z = +1.71) to 163 cm (z = +1.80), Tanner from G2P2T2 to G3P3T1, penis from 3.5 to 5.5 cm, LH from 4.8 to 12.4 IU/L (NR: 1.5 to 9.3 IU/L), testosterone from 259 to 1,069 ng/dL (NR: 165 to 763 ng/dL), estradiol from 28 to <5.0 pg/mL (NR: < 40 pg/mL) and bone age remained at 12.5 years. Case 3 (p.Ser597Arg): Onset of treatment at age 12; height changed from 153 cm (z = +0.49) to 161 cm (z = +0.55), Tanner from G2P2T1 to G3P3T1, penis from 4.0 to 7.0 cm, LH from 8.5 to 17.2 IU/L (NR: 1.5 to 9.3 IU/L), testosterone from 280 to 889 ng/dL (NR: 165 to 763 ng/dL), estradiol from 32 to <5.0 pg/mL (NR: < 40 pg/mL) and bone age remained at 13.5 years. Discussion: There are no reports in the literature of the use of aromatase inhibitor in PAIS. The results of this pilot study (gynecomastia regression, significant testosterone level increases with decrease in estradiol levels, increment in height without bone age advancing, progression of puberty and penile growth) are sustaining for the indication of this treatment in boys with PAIS during puberty.
