Comparison of the suppressive capacity of different depot gonadotropin-releasing hormone analogs in women.

Abstract

Different depot GnRH analogs (GnRH-A) are currently used for the reversible suppression of the pituitary-ovarian axis in several reproductive and neoplastic disorders in women. In spite of anecdotal reports of incomplete suppression by some depot GnRH-A, this issue has never been systematically investigated in adult women. Thus, we elected to study 40 normally cycling women with male-related infertility or benign reproductive disorders; each group of 10 subjects received a different GnRH-A for 3 months: buserelin (group B; 300 micrograms, sc, every 12 h, as a control), goserelin (group G; 3.6 mg, sc, every 28 days), leuprorelin (group L; 3.75 mg, im, every 28 days), and triptorelin (group T; 3.75 mg, im, every 28 days). Depot GnRH-A was administered by one of the investigators. GnRH tests (100 micrograms, iv) were performed before treatment (cycle day 7; test A) and on treatment days 57 (i.e. 1 day after the third depot GnRH-A; test B) and 84 (i.e. 28 days after the third depot GnRH-A; test C). Immunoreactive (i) LH levels were measured with an ultrasensitive immunochemiluminometric assay. Profound suppression of the iLH response to the GnRH test occurred in all subjects during treatment. Conversely, FSH levels in the third month of treatment tended to be higher in the depot GnRH-A groups than in group B, and this difference achieved statistical significance (P < 0.05) in groups G and L during test C. In GnRH test B, while the mean estradiol (E2) level was less than 75 pmol/L (< 20 pg/mL) in all group B subjects, individual E2 levels were greater than 75 pmol/L in five patients receiving depot GnRH-A (two in group G, one in L, and two in T). Finally, individual E2 levels during test C were greater than 75 pmol/L in only two patients of group G, who also reported vaginal spotting. Thus, we conclude that in adult women, 1) iLH was profoundly suppressed in the third month of administration of all GnRH-A tested; 2) FSH suppression with depot GnRH-A was less marked than that with high-dose short-acting sc buserelin; and 3) signs of an incomplete block of ovarian function can be present in the third month of depot GnRH-A administration, particularly when goserelin is employed.

Estrogen suppression in premenopausal women following 8 weeks of treatment with exemestane and triptorelin versus triptorelin alone

“…Plasma concentrations of E 2 markedly higher than the castration level of 20 pg/ml [10] were observed in 2 subjects (1 per treatment group) on day 29 before the injection of the second T dose, indicating that chemical castration had not been achieved in these individuals after the first T dose. Because the study was designed to evaluate the additional estrogen suppression achieved by treatment with EX following chemical castration, the data from these 2 subjects were not included in the pharmacodynamic analysis.…”

“…In addition, there is evidence that in premenopausal women who have experienced disease progression while taking goserelin plus tamoxifen, a switch to the aromatase inhibitor anastrozole can reduce peripherally circulating estrogen by an additional 76%, with corresponding clinical benefit [19]. Exemestane is an orally active selective aromatase inhibitor that is structurally related to the natural substrate androstenedione [10,20,21]. EX is widely used for the treatment of advanced breast cancer in postmenopausal women in whom antiestrogen therapy has failed and as adjuvant therapy in postmenopausal women with hormone receptor-positive early breast cancer who have received 2-3 years of tamoxifen [8,9,22].…”

Differences in serum LH and FSH levels using depot or daily GnRH agonists in controlled ovarian stimulation: influence on ovarian response and outcome of ART

“…The amount of LH available for ovarian stimulation depends on the intensity of pituitary suppression and the dose of exogenous LH. Differences in various GnRHa concerning intensity, onset and duration of pituitary suppression have been demonstrated previously (11)(12)(13). A recent meta-analysis did not demonstrate significant differences between patients treated with depot or daily GnRH agonists in terms of pregnancy rate, but number of gonadotrophin ampoules and duration of stimulation (14).…”

The role of ovarian ablation in the adjuvant therapy of breast cancer

“…Similar effects on the suppression of luteinizing hormone and estradiol (E2) were observed at the end of 3 months of therapy with buserelin, goserelin, leuprolide, and triptorelin in 38 of 40 normal-cycling women [31]. However, higher levels of E2 and FSH were observed at the end of an 84-day period in two patients treated with the monthly version of goserelin [31]. This could be explained by the rapid peak (within 2 weeks of administration) reached by goserelin as it is released from its rod-shaped lactic-glycolic copolymer carrier, with low levels during the early and late phases in contrast to the analogue-release dynamics of other microencapsulated LH-RH formulations [31].…”

“…Parinaud et al [29] demonstrated comparable pregnancy rates in an in vitro fertilization program comparing short-acting buserelin, triptorelin, and leuprolin; similarly, Lindner et al [30] reported no differences in the suppressive capabilities of goserelin, buserelin, triptorelin, and leuprolin. Similar effects on the suppression of luteinizing hormone and estradiol (E2) were observed at the end of 3 months of therapy with buserelin, goserelin, leuprolide, and triptorelin in 38 of 40 normal-cycling women [31]. However, higher levels of E2 and FSH were observed at the end of an 84-day period in two patients treated with the monthly version of goserelin [31].…”