The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Jan 1992
Clinical Trial Controlled Clinical TrialDepot gonadotropin-releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception.
Thus far, when tested as male contraceptives, GnRH agonists in combination with androgens were not very effective in producing azoospermia. Since in previous studies androgens were always given simultaneously with the GnRH agonist or later, we tested whether GnRH agonist administration after an initial androgen suppression phase might yield better results. After a control period, 3 groups of young healthy men (n = 8/group) received an initial loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), followed by 200 mg of the ester every 3 weeks for 24 weeks. ⋯ After 30 weeks, when the maximal suppression of spermatogenesis was seen, 4 of 8 volunteers in the group treated with 19NT-HPP alone were azoospermic, and the remaining 4 volunteers were oligozoospermic. In the groups treated with 19NT-HPP/buserelin, no more than 4 of 16 volunteers were azoospermic, and no more than 8 of 16 volunteers were oligozoospermic at any time point. It is concluded that GnRH agonist depot preparations have a blunting effect on the suppression of pituitary and testicular function caused by androgens in men participating in contraceptive trials.
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J. Clin. Endocrinol. Metab. · May 1991
Endocrine response determines the clinical outcome of pulsatile gonadotropin-releasing hormone ovulation induction in different ovulatory disorders.
To accrue systematic information in different ovulatory disorders on the precise relationship among endocrine response, clinical outcome, and the occurrence of complications, we treated 114 patients with pulsatile GnRH (2.5-5.0 micrograms, iv, every 60 min) for 187 cycles and compared them to 20 normal menstrual cycles. Thirty of these patients had primary hypogonadotropic amenorrhea (PHA; 40 cycles), 33 had other forms of hypogonadotropic hypogonadism (HH; 55 cycles), and 51 had polycystic ovary syndrome (PCOS; 92 cycles). Daily blood samples were drawn for hormone determinations. ⋯ Finally, GnRH analog suppression in PCOS permitted normalization of the follicular phase endocrine pattern, achievement of good ovulatory (76%) and pregnancy (28%) rates, and avoidance of multiple pregnancies; however, luteal phase steroid secretion was abnormal, and the abortion rate remained elevated (43%). Obesity was associated with a reduced ovulatory rate in PCOS, but not in hypogonadotropic, subjects. Thus, we can conclude that in pulsatile GnRH ovulation induction: 1) a profound hypogonadotropic condition, whether spontaneous as in PHA or induced with GnRH analogs as in other ovulatory disorders, is associated with optimal menstrual cycle restoration, high ovulatory and conception rates, and virtually absent risks of multiple pregnancy; 2) residual hypothalamic activity in HH may be responsible for supraphysiological pituitary-ovarian stimulation and result in multiple pregnancy unless a low GnRH dose (2.5 micrograms/bolus) or GnRH analog pretreatment is employed; 3) obesity does not affect treatment outcome in hypogonadotropic patients; and 4) the high spontaneous abortion rate in PCOS may be related to corpus luteum dysfunction.
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J. Clin. Endocrinol. Metab. · Apr 1991
Comparative StudySerum luteinizing hormone concentrations, as measured by a sensitive immunoradiometric assay, in children with normal, precocious or delayed pubertal development.
To determine the diagnostic potential of a highly sensitive immunoradiometric assay (IRMA) for LH in children with normal puberty or altered tempo of sexual maturation, we compared serum LH levels by IRMA (LH IRMA) and standard RIA (LH RIA) in children with idiopathic precocious thelarche (IPT; n = 6), idiopathic premature adrenarche (IPA; n = 14), central precocious puberty (CPP; n = 15), and constitutional delay of puberty (DP; n = 15), and 160 control children (79 males and 81 females). Subjects in the latter group were staged, according to their genital or breast development, as early prepubertal (P1E; age, less than 8 yr), late prepubertal (P1L; 8-12 yr), or stage II-V (P2-P5; n = 22-34 for each subgroup). Serum LH IRMA levels in P1E, IPT, and IPA children were either undetectable (95% of subjects less than 0.25 IU/L) or barely detectable (5% of subjects, less than or equal to 0.5 IU/L). ⋯ From P1E to P5 LH IRMA levels increased 38-fold in females and 21-fold in males, while LH RIA increased 4- and 2.1-fold, respectively. Serum LH IRMA correlated significantly with serum testosterone levels in boys from P1L to P5 (r = 0.76; P less than 0.001), while LH RIA levels did not (r = 0.18). Serum LH IRMA concentrations were above the prepubertal range (greater than 0.5 IU/L) in 67% of children with CPP (group average, 1.8 +/- 1.4 IU/L) and 87% of children with DP (1.6 +/- 1.4 IU/L).(ABSTRACT TRUNCATED AT 400 WORDS)
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J. Clin. Endocrinol. Metab. · Apr 1991
Hormonal profiles of natural conception cycles ending in early, unrecognized pregnancy loss.
Loss of a conceptus early in development can be detected by very sensitive assays specific for hCG. We examined 20 menstrual cycles ending in early loss of a conceptus in order to identify hormonal correlates of loss. Each loss cycle was compared to a successful conception cycle in the same woman, using daily concentration of urinary estrone-3-glucuronide and pregnanediol-3-glucuronide (PdG). ⋯ The corpus luteum responded to the conception in only 2 of the 10 loss cycles with late implantation. In contrast, the corpus luteum responded in 8 of 10 loss cycles with normally timed implantation. The similarity of preimplantation hormonal profiles in cycles of early pregnancy loss and in cycles with successful conceptions suggests that most early losses in reproductively normal women do not result directly from deficiencies in ovarian steroid production.
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J. Clin. Endocrinol. Metab. · Dec 1990
Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women.
Women with ovarian hyperandrogenism frequently have insulin resistance, whose underlying mechanism remains to be determined. In the present study we have investigated the relationship between insulin sensitivity and the acute effect of endogenous insulin secretion on circulating androgen levels. Insulin sensitivity, glucose-mediated insulin release, and glucose/insulin-stimulated androgen responses were determined during a frequently sampled iv glucose tolerance test in a group of 19 women with clinical evidence of polycystic ovary syndrome (PCOS) and 9 age- and weight-matched controls. ⋯ Other androgen levels showed a modest nonsignificant decline during the study in PCOS and control groups. These findings confirm the weight-independent insulin resistance of some hyperandrogenic women. The failure of glucose-stimulated endogenous insulin secretion to significantly depress DHEA levels in insulin-resistant women with PCOS may account in part for their androgen excess.