Endogenous catecholamines suppress thyrotropin secretion during the early follicular phase of the menstrual cycle.

The physiological role of hypothalamic catecholamines in the regulation of TSH secretion in humans has not been studied extensively. We administered the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (AMPT) to five women in the early follicular phase (one of menstrual cycle days 2-5) of the menstrual cycle and compared TSH secretion patterns to those in five women at the same time in the cycle who did not receive AMPT. From 0800-1600 h, volunteers had an i.v. line placed, through which blood was withdrawn every 15 min for TSH and PRL determinations. AMPT (500 mg) was administered to the study group at 0800 h and again at 1000 h. Baseline TSH concentrations at 0800 h were not significantly different between the control and treatment groups. In keeping with its characteristic circadian secretion pattern, TSH in the control group was 1.72 +/- 0.23 mIU/L at 0800 h, declined to 1.02 +/- 0.11 mIU/L by 1600 h, and was significantly less than the 0800 h value at all time points beyond 1115 h. The decline in TSH was observed in all five controls. By contrast, TSH in the AMPT group rose from an 0800 h value of 1.99 +/- 0.09 mIU/L to a peak of 3.30 +/- 0.86 IU/L by 1245 h, and was significantly higher than that at 0800 h in the treated group from 1130-1315 h. The increase in TSH was observed in all five women who received AMPT. There were significant differences between the mean TSH concentrations in the AMPT-treated (2.51 +/- 0.09 mIU/L) vs. the control group (1.28 +/- 0.09 mIU/L; P < 0.0001) for the entire study. The effectiveness of AMPT was demonstrated by an elevation of mean PRL concentrations from a baseline of 16.67 +/- 2.55 micrograms/L to a peak of 138.7 +/- 21.6 micrograms/L. We conclude that endogenous catecholamines tonically inhibit TSH secretion in the early follicular phase. These data suggest modulation of TRH by tuberoinfundibular dopamine at the hypothalamic and/or pituitary level.

Predicting and optimizing success in an intra-uterine insemination programme.

We analysed 381 consecutive cycles of homologous intrauterine insemination (IUI) in 215 infertile couples, resulting in 48 pregnancies (12.6%/cycle, 22.3%/patient). Cycle fecundity ranged from 0.11 to 0.14 in women aged 25-39 years, falling to 0.04 beyond age 40 years. Of the 48 pregnancies, 43 occurred in the first three treatment cycles, in which fecundity was 0.14, 0.16 and 0.10 respectively. Beyond three cycles, fecundity was 0.07 (P = 0.05 versus first two cycles). The occurrence of pregnancy varied with diagnosis (P = 0.04). Fecundity was significantly greater for women with ovulatory dysfunction (0.30) than for endometriosis, male factor, tubal factor, idiopathic infertility or multifactorial (0.08-0.14). Ovulation induction using menopausal gonadotrophins offered significant advantage over natural cycles or cycles using clomiphene citrate without gonadotrophins (0.15 versus 0.03, P = 0.01). Cycles in which pre-ovulatory surges were either induced or supported with human chorionic gonadotrophin (HCG) were superior to spontaneous luteinizing hormone surges (0.13 versus 0.03, P = 0.05). Recruitment of at least two mature (> 1.6 cm) follicles was critical. Only one pregnancy occurred in 64 cycles characterized by one mature follicle, compared with a pregnancy rate of 0.15 in cycles characterized by two or more mature follicles (P = 0.006). IUI is not beneficial to women > 40 years old, and has the best chance of success within three cycles. Multiple follicle recruitment using gonadotrophin-based stimulation protocols and mid-cycle HCG are necessary to achieve an acceptable pregnancy rate.

Inhibition of endogenous catecholamine synthesis augments early follicular phase luteinizing hormone secretion.

The physiological role of catecholamines, particularly dopamine and norepinephrine, in the regulation of gonadotropin secretion in humans is unclear. We administered the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT, 500 mg at 800 and 1000 h) to five women in the early follicular phase of the menstrual cycle and compared LH secretion patterns to those in five untreated controls. Commencing at 800 h, blood was drawn every 15 min for LH and PRL measurements until 1600 h. AMPT elevated PRL concentrations (mean +/- SEM) from a baseline of 14.72 +/- 2.51 micrograms/L to a peak of 102.2 +/- 24 micrograms/L. LH concentrations [21.97 +/- 0.56 (AMPT) vs. 13.51 +/- 0.16 IU/L (control), P less than 0.0001], LH area under the curve [11014 +/- 1815 (AMPT) vs. 7009 +/- 404 IU.min/L (control), P = 0.05] and LH pulse amplitude [9.99 +/- 2.38 (AMPT) vs. 4.03 +/- 0.61 IU/L (control), P = 0.04] were all greater in the group in which catecholamine synthesis was inhibited. There was no difference in pulse frequency between the groups (7.4 +/- 0.51 vs. 6.6 +/- 0.24 pulses/8 h, P greater than 0.05). We conclude 1) inhibition of endogenous catecholamine synthesis augments LH levels in the early follicular phase, and 2) increased LH secretion during catecholamine synthesis inhibition is due, at least in part, to increased LH pulse amplitude but not increased LH pulse frequency.