CROSS GENOTYPE SEX-HORMONE TREATMENT IN 2 CASES OF HYPOGONADAL OSTEOPOROSIS

Background: Sex hormone deficiency is the most common cause of bone lo ss. Reduced bone mass and an increased risk for osteoporotic fractures have been described in hypogonadal subjects of both sexes. We present here the results of treating two patients showing abnormal sexual dif ferentiation (an XX male and an XY female), who suffered from bone los s related to sex hormone deficiency, with cross genotype sex hormones. Subjects and Methods: Patient 1 was an asymptomatic 39-yr-old XY fema le with complete androgen insensitivity. Her testes had been removed, and she later discontinued estrogen treatment. Patient 2, a 37-yr-old XX male, had congenital adrenal hyperplasia, which led to a masculine phenotype. He was ovariectomized and reared as a male. He was treated with glucocorticoids but refused androgen treatment for many years. We treated both patients with phenotypically matched sex hormones (patie nt 1 received conjugated estrogens 1.25 mg/day, and patient 2 received 250 mg testosterone every 4 weeks) and followed their bone mineral de nsity (BMD) using dual-energy X-ray absorptiometry, urine calcium, and hydroxyproline excretion. Results: Before treatment both patients had low sex hormones and highly elevated gonadotropins. As a result of tr eatment urine hydroxyproline excretion decreased from 45 and 26.7 mg/g creatinine to 15 and 15.9 mg/g creatinine in patients 1 and 2 respect ively. In patient 1, lumbar BMD rose from 0.1912gr/cm(2) to 0.976gr/cm (2) and femoral neck BMD rose from 0.716gr/cm(2) to 0.836gr/cm(2) afte r 4 years of treatment. In patient 2, lumbar BMD rose from 0.717gr/cm( 2) to 0.815gr/cm(2) and the femoral neck BMD rose from 0.509gr/cm(2) t o 0.635gr/cm(2) after 27 months of treatment. Conclusions: Phenotypica lly-matched sex hormone therapy in patients with abnormal sexual diffe rentiation is essential not only to maintain external appearance but a lso for the preservation of bone mass.