Biomedical subjects

G Kuroda

Publications and source records attributed to G Kuroda.

7 recordsLinked to original sources

PubMed1988

Continuous subcutaneous infusion of human menopausal gonadotropin in anovulatory women with decreased FSH/LH ratio and androgen excess.

Ten women of polycystic ovarian-type (PCO-type) anovulation, having a decreased ratio of FSH to LH and androgen excess, resistant to the previous clomiphene, bromocriptine and/or daily im injections of human menopausal gonadotropine (hMG), were treated with continuous sc infusion of 150 IU/day hMG. The treatment was initiated on cycle day 2-5 and continued until the dominant follicle reached 20 mm or more in diameter, when an im bolus of 10,000 IU human chorionic gonadotropin was given. The treatment elevated the geometric mean of pretreatment serum FSH (8.6 mIU/ml) to 15.9 mIU/ml (p less than 0.001), while serum LH decreased from 29.4 mIU/ml to 20.7 mIU/ml (p less than 0.01). This resulted in a highly significant increase in the FSH/LH ratio from 0.29 to 0.77 (p less than 0.0001). Follicle enlargement was demonstrated in 13 of the 14 treatment cycles, 12 of which were ovulatory. Pregnancy ensued in 4 cases, 1 of which was a quadruplet pregnancy. Continuous infusion of hMG was indicated as an effective way of inducing ovulation in PCO-type anovulation resistant to conventional methods of ovulation induction.

Adult↗

PubMed1988

Bromocriptine treatment in anovulation with decreased ratio of follicle stimulating hormone to luteinizing hormone and with hyperandrogenism.

Twenty-six anovulatory women of polycystic ovarian (PCO)-type were treated with bromocriptine (Br) at a daily dose of 5 mg for 2 months. Ovulatory cycles were resumed in 18 (69.2%) women (Br-responders). No difference between pretreatment serum levels of FSH, LH, PRL and estradiol and FSH/LH ratios in Br-responders and nonresponders was observed. The geometric mean of circulating androstenedione (A-dione) in Br-responders (2.58 ng/ml) appeared higher than that in nonresponders (2.11 ng/ml) but was not statistically significant. The geometric mean of dehydroepiandtrosterone sulfate (DHEA-S) in Br-responders (1652 ng/ml) was lower (p less than 0.01) than that in nonresponders (2582 ng/ml). The ratio of DHEA-S to A-dione (D/A ratio) exhibited a highly significant between-group difference (p less than 0.001) (646 and 1222 for Br-responders and nonresponders, respectively). Br-nonresponders with high DHEA-S levels and D/A ratios tended to hyperproduction of adrenal androgen, and Br-responders with high A-dione levels and low D/A ratios to hyperproduction of ovarian androgen. The present study indicates that Br is effective in PCO-type women presumably with ovarian androgen hyperproduction. The efficacy of Br, when applied to PCO-type women, could be predicted with their D/A ratios.

Adult↗

PubMed1987

[Ovulation induction with pulsatile gonadotropin-releasing hormone and continuous human menopausal gonadotropin in polycystic ovarian disease].

Various treatments have been applied to polycystic ovarian (PCO) type of anovulation. However, none of them was definitive in terms of the efficacy and side effects. Six anovulatory women of PCO type were treated with pulsatile gonadotropin-releasing hormone (GnRH) of various pulse intervals and continuous human menopausal gonadotropin (hMG). The efficacy and rationale of the treatments were discussed. The subjects were diagnosed PCO by GnRH test and/or laparoscopy. They did not ovulate with clomiphene, clomiphene-hCG and hMG-hCG therapies. Their pretreatment serum FSH and LH levels and FSH/LH ratios were 6.9 +/- 1.2 mIU/ml, 15.7 +/- 5.1 mIU/ml, and 0.54 +/- 0.19 (Mean +/- SD), respectively. The treatment consisted of 3 protocols: 1) pulsatile GnRH (5-10 micrograms/pulse) of 90 min interval, 2) pulsatile GnRH (5-10 micrograms/pulse) of 120 min interval and 3) continuous hMG (150 IU/day) through subcutaneous route. Follicular growth was monitored sonographically and an intramuscular bolus of 10,000 IU hCG was given when the dominant follicle reached 20 mm in diameter. During both GnRH treatments serum FSH levels and FSH/LH ratios did not elevate substantially. Serum LH, E2 and PRL levels elevated acutely and transiently during the initial phase of GnRH treatments. Follicular growth was observed in a small fraction of the cases, but none of them ovulated. In contrast, continuous hMG treatment induced significant elevation in serum FSH levels (8.2 +/- 1.7 mIU/ml; p less than 0.01) and FSH/LH ratios (1.73 +/- 0.57; p less than 0.001). Transient hyperprolactinemia was accompanied with the preovulatory E2 rise. All the cases ovulated and 3 singleton pregnancies followed. These findings draw conclusions as follows. Pulsatile GnRH administration may desensitize the pituitary presumably due to increased GnRH pulse frequency as a consequence of two independent pulse generators, intrinsic and exogeneous. It may induce transient hyperprolactinemia through a paracrine system between gonadotrophs and lactotrophs. As a due course pulsatile GnRH therapy is questionable for ovulation induction in cases with functioning hypothalamic-pituitary axis. The fact that continuous hMG effectively induced follicle maturation with elevated FSH/LH ratios suggested that FSH dominance might be a prerequisite for folliculogenesis. The fluctuating nature of gonadotropins might not be mandatory for folliculogenesis.

Adult↗

PubMed1987

[Transient hyperprolactinemia during ovulation induction with gonadotropin releasing hormone (GnRH) pulsatile administration].

Seven clomiphene-resistant normoprolactinemic anovulatory patients were treated with GnRH pulsatile administration (total 15 treatment cycles). Several problems with GnRH pulse therapy were raised through 6 unsuccessful cases. In 5 cases (10/15 treatment cycles), transient hyperprolactinemia (50-100 ng/ml) appeared immediately after the initiation of the treatment and persisted for 6-10 days. Follicle maturation and ovulation was not induced in these cases. Frequent blood sampling failed to demonstrate GnRH-induced LH secretion in 3 cases. Synchronous secretion of PRL with LH was observed when serum PRL levels were low, but not in situations with elevated serum PRL levels. The lack of GnRH-induced LH secretion indicates the down-regulation of the pituitary with increased frequency of GnRH pulses due to intrinsic and exogenous GnRH. The synchrony of LH and PRL suggests the contribution of GnRH-mediated PRL releasing factor (PRF) through a paracrine system between gonadotrophs and lactotrophs. Transient hyperprolactinemia observed in the current study might be attributable to a relative increase in GnRH to a GnRH-associated peptide (GAP), a constituent of GnRH prohormone and possessing an intrinsic effect of PRL suppression, by exogenously administered GnRH, causing overwhelming superiority of GnRH-mediated PRF. Transient hyperprolactinemia and regulation of the pituitary may hamper ovulation induction with GnRH pulse therapy when applied to cases with intact hypothalamic-pituitary axis.

Anovulation↗

PubMed1986

On the short-loop feedback regulation of the hypothalamic luteinizing hormone releasing hormone 'pulse generator' in the rhesus monkey.

The characteristic electrophysiological manifestations of LHRH 'pulse generator' activity were unaffected by prolonged elevations in plasma LH concentrations achieved by the administration of a long-acting LHRH agonist. These findings do not lend support to the existence of a 'short-loop feedback' inhibition of LHRH 'pulse generator' activity by LH.

Animals↗

PubMed1986

The effect of morphine on the electrophysiological activity of the hypothalamic luteinizing hormone-releasing hormone pulse generator in the rhesus monkey.

In ovariectomized rhesus monkeys, the electrophysiological manifestation of luteinizing hormone-releasing hormone (LHRH) pulse generator activity was arrested by morphine and reinitiated by naloxone. These responses were noted within 1 and 2 min, respectively, after the intravenous injection of the drugs. Naloxone given alone had no effect. These results support the view that opioids modulate pulsatile gonadotropin release by an action on the hypothalamic LHRH pulse generator.

Animals↗

PubMed1986

Ovulation induction with bromocriptine in normoprolactinemic anovulatory women.

Afternoon-evening and nocturnal serum PRL levels and PRL responsiveness to metoclopramide (MCP) were determined in 34 women with normoprolactinemic anovulation (nPRL-Anov) and in the early follicular phase (EFP) in 6 normal women. Subsequently, the nPRL-Anov women were treated with 5 mg bromocriptine (Br) twice daily for 2 months, and its action on ovulation was determined. Those women who did not respond to Br received 50-150 mg clomiphene for 5 days. The nPRL-Anov patients were classified into 3 groups in terms of the efficacy of Br treatment: group I, those who ovulated with Br (n = 13); group II, those who ovulated after receiving Br and clomiphene (n = 7); and group III, those who failed to ovulate after the above treatments (n = 10). Four patients dropped out of the study. Diurnal serum PRL levels were approximately 10 ng/ml in all patients, and no statistical difference was found among the groups. Peak nocturnal serum PRL levels (the highest PRL value during the 0000-0400 h period) were 38.0 +/- 23.9 (+/- SD) ng/ml in group I patients, higher (P less than 0.05) than in groups II and III and normal (EFP) women (20.1 +/- 9.1, 20.7 +/- 7.7, and 16.3 +/- 2.7 ng/ml for the group II and III patients and the EFP women, respectively). MCP induced rapid and marked elevation in serum PRL levels in all subjects. The maximum post-MCP PRL value in the group I patients was 224.2 +/- 89.7 ng/ml, which was significantly higher (P less than 0.002) than the maximum value in the remaining groups (120.5 +/- 25.8, 121.3 +/- 54.2, and 101.9 +/- 28.1 ng/ml, respectively). Ten (76.9%) and 12 (92.3%) group I patients had nocturnal PRL levels above 25 ng/ml and maximum PRL values after MCP above 150 ng/ml, respectively. We conclude that some nPRL-Anov patients have elevated nocturnal serum PRL levels or enhanced PRL responsiveness to MCP, indicative of nocturnal or latent hyperprolactinemia. Br effectively induced ovulation in these patients. A MCP provocation test can predict the outcome of Br treatment in such nPRL-Anov patients.

Adult↗