Effectiveness and long-term safety of prolonged gosereline and tibolone in women with endometriosis

Gonadotropin-releasing hormone (GnRH) agonists are widely administered to treat endometriosis, but generally are not prescribed for more than 6 months since they are associated with vasomotor symptoms and bone loss. A GnRH agonist and steroid add-back therapy can be given for longer times without flare-up or significant hypoestrogenic symptoms. We examined the efficacy and safety of a weak estrogenic steroid, OD14, with prolonged goserelin treatment in seven regularly menstruating women (age 26-33 yrs) with laparoscopically diagnosed, symptomatic endometriosis. The women received goserelin 3.65 mg subcutaneously/month and 2.5 mg OD14 2.5 mg/day beginning in the fourth cycle for 18 to 20 months. The frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were scored by the women on a scale of 0 to 6 and compared. Samples of blood and urine were obtained to measure serum estradiol (E2) levels, lipids, and urinary calcium:creatinine (Ca:Cr) ratios at the start of treatment and monthly thereafter. The vasomotor scores, serum E2 levels, and urine Ca:Cr ratios were consistent with the hypoestrogenism induced by goserelin (24.2 ± 3.1, 18.5 ± 7.2 pg/ml, and 0.063 ± 0.008, respectively). The decreases in vasomotor scoring with regard to hot flushing, sweating, and urinary Ca:Cr ratios were significant after adding OD14 (14.8 ± 2.2, 0.031 ± 0.005, p 0.05) throughout therapy. The increased low-density:high-density lipoprotein ratio with goserelin improved with OD14, remaining at the lower limit of normal. Thus, OD14 add-back to GnRH agonist therapy enabled us to extend medical therapy of endometriosis longer than 6 months, preventing hypoestrogenic side effects, and with adequate suppression endometriosis symptoms.