Tamoxifen Treatment for Pubertal Gynecomastia in a Patient with Partial Androgen Insensitivity Syndrome

Introduction: Androgen insensitivity syndrome (AIS) is a sex development disorder that causes varying degrees of virilization defects in 46,XY individuals. The cases diagnosed with partial AIS (PAIS) can present with many different clinical findings including ambiguous genitalia from female phenotype with cliteromegaly to male phenotype with hypospadias, cryptorchidism, azoospermia, and pubertal gynecomastia. In PAIS patients, pubertal gynecomastia can develop and affect the quality of life. There is no standard protocol for its treatment. Here, we discussed a PAIS patient with pubertal gynecomastia and the effect of tamoxifen, a pure estrogen receptor modulator, in treatment.
Case: The patient admitted to our clinic at 3.2 years of age with ambiguous genitalia and his physical examination revealed Sinnecker stage 3 genital phenotype. Gonads were bilateral testis, internal genitalia were male, and karyotype was 46,XY. There was no testosterone synthesis problem that was revealed with human chorionic gonadotropin stimulation test (stimulated total testosterone: 532 ng/dL). Androgen receptor gene analysis showed two silent mutations (no amino acid changes) in exon 1 (p.Glu213Glu) and exon 7 (p.Ile817Ile). Corrective operations for cryptorchidism and hypospadias were performed and testosterone and dihydrotestosterone gel were used for the treatment of micropenis. When the patient was 12.3 years old, bilateral gynecomastia was observed at stage T3. At 13.5 years old, gynecomastia advanced to stage T4 and tamoxifen treatment 20 mg/day was started. After six months of the therapy, the dose was increased to 40 mg/day. At the 7th month of treatment, a dramatic regression of gynecomasty was observed.
Results: In PAIS patients with pubertal gynecomastia, difficulties in treatment may be observed. Surgery is not recommended because of the side effects such as skin retraction, hypertrophic scar, hypesthesia, and skin excess. Tamoxifen treatment can be an effective therapeutic option especially in PAIS patients with significant pubertal gynecomastia.