Nafarelin

Plasma 17-hydroxyprogesterone (17PROG) hyperresponsiveness to GnRH agonist (nafarelin) testing is typical of polycystic ovary syndrome and other functional ovarian hyperandrogenism (FOH) that does not meet customary criteria for the diagnosis of polycystic ovary syndrome. We have postulated that this results from abnormal regulation of androgen secretion. Whether this dysregulation is the result of a normal physiological response to ovarian hyperstimulation or escape from down-regulation of steroidogenesis is unknown. To distinguish between these possibilities, we have analyzed the ovarian steroid responses to nafarelin for the apparent efficiency of the steroidogenic steps and the apparent dose-response relationships between blood LH and steroid levels. We compared normal women (n = 18) with three groups of hyperandrogenic women (n = 15-19/group): patients with 17PROG hyperresponsiveness with or without elevated LH levels (type 1 and type 2 FOH, respectively) and patients with normal 17PROG responses to nafarelin (nafarelin negative). Subjects were pretreated with dexamethasone to suppress coincidental adrenal contributions to plasma steroid levels. The pattern of steroid secretion was similarly abnormal in both types of FOH, with the high LH group having generally more severe abnormalities in the levels of steroid intermediates.

Administration of GnRH agonist for an extended period inhibits pulsatile LH release but enhances testicular function of bulls. The mechanism whereby long-term administration of GnRH agonist enhances testosterone concentration in the blood of bulls has not been determined. The aim of this study was to determine whether chronic treatment with the GnRH agonist, azagly-nafarelin, increases blood concentrations of LH and FSH in prepubertal bulls. Two different doses of the GnRH agonist were administered via Alzet mini-osmotic pumps for 28 days. Blood samples were collected at 20 min intervals for 24 h at days 2, 13 and 25 of treatment. Agonist-treated groups had reduced testosterone pulse frequency (P < 0.05) and increased mean and basal concentrations of testosterone (P < 0.05) compared with untreated control bulls. Basal LH concentrations were higher in agonist-treated bulls during all three periods (P < 0.05) and overall (1 ng ml(-1) higher, compared with control bulls; P < 0.001). Frequency of LH pulses in the agonist-treated groups was reduced to less than one pulse in 24 h. Agonist-treated bulls tended to have (P < 0.10) or had (P < 0.05) a slight but significant increase in blood FSH concentration.

The effects of nafarelin (400 micrograms daily; 12 patients) and danazol (600 mg daily; 6 patients) on serum lipoproteins, high density lipoprotein (HDL) subfractions, and apoproteins-A-I and -A-II were studied. Lipoproteins were fractionated by sequential flotation from samples taken before and after 1, 3, and 6 months of treatment as well as 3 months after cessation of medication. Serum concentrations of estradiol, total and free testosterone, androstenedione, and sex hormone-binding globulin were also determined. On nafarelin treatment, serum total HDL and HDL2 cholesterol concentrations increased slightly, but total and low density lipoprotein (LDL) cholesterol levels were unchanged. There was no effect on apoproteins-A-I and -A-II or on total and very low density lipoprotein (VLDL) triglyceride concentrations. During treatment with danazol, the serum levels of total HDL and HDL2 cholesterol showed profound decrease, as did all the components of HDL2, including apoprotein-A-I. Concomitantly, the total mass of LDL was increased by 25%, accounted for by parallel rises in all of the components of LDL. Total and VLDL triglyceride concentrations decreased inconsistently. Both treatments resulted in hypoestrogenism of the same degree.