Endocrine and clinical effects of estradiol and testosterone pellets used in long-term replacement therapy

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Ten women with estrogen deficiency symptoms because of premature menopause [3], gonadal dysgenesis [3], or surgical menopause [4] received subcutaneous implants consisting of 25–75 mg estradiol (E 2) with or without 75 mg testosterone (T). All had elevated plasma FSH, and LH, and low E 2 prior to treatment. Plasma levels of FSH, LH, E 2, T and estrone (E 1) were measured by specific radioimmunoassay techniques prior to treatment, three times a week for the first week and once a week for up to 76 weeks after implantation. Mean plasma E 2 levels rose abruptly and reached a maximum of 190 ± 35 pg/ml within 2 weeks. They fluctuated around 150 pg/ml for 46 weeks, then gradually declined, but remained above pretreatment values for more than 68 weeks. Plasma E 1 increased to a lesser extent resulting in E 2 : E 1 ratio between 1 and 5. Elevated FSH and LH titers became suppressed within 4–6 weeks. The lowest average E 2 increase occurred after 25 mg implant and was associated with incomplete FSH and LH suppression. There were no differences in maximal E 2 levels reached after 50 mg or 75 mg implant, however, after 75 mg implant, E 2 levels appeared less variable and were sustained for a longer period of time, averaging 125 pg/ml for 70 weeks. Plasma FSH and LH concentrations were suppressed below pretreatment levels in all patients. The degree of suppression was related to the dose of E 2 implanted and, therefore, to plasma E 2 levels. The FSH and LH suppression appeared more complete in women with gonadal dysgenesis than in those with premature or natural menopause. Plasma T rose abruptly to a peak mean level of 2.5 ± 1.6 ng/ml within 2 weeks of implantation. A precipitous and steady decline with return to preimplantation titers between 17th and 18th week were then observed. The E 2 : E 1 ratio during the first 18 weeks after implantation was significantly higher in women who received E 2 implant alone than in those who received E 2 + T implant. Clinically, all patients had symptomatic improvement within 24–48 hours. Regular withdrawal bleeding followed administration of oral progestogen for up to 76 weeks after implantation in six patients with intact uterus.