Women In Early Follicular Phase Research Articles

Aromatase inhibition causes increased amplitude, but not frequency, of hypothalamic-pituitary output in normal women

To better understand the site and mode of action of aromatase inhibitors. Prospective study. Academic research environment. Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47±0.68 kg/m2), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8±1.7 kg/m2) as historical controls. 2.5 mg letrozole daily for 7 days, with daily urine collection (first morning void), thrice weekly blood sampling, and 4 hours of blood sampling every 10 minutes. Serum luteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests. Mean LH and LH pulse amplitude more than doubled in the women who had taken letrozole compared with the controls, but the LH pulse frequency did not differ between the women taking letrozole and the controls. These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that the mean LH and LH pulse amplitude, but not the frequency, increased after letrozole suggests a possible pituitary site of action.

The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea

The purpose of this work was to revisit the gonadotrophin insufficiency of functional hypothalamic amenorrhoea (FHA) with the use of relevant ovarian markers. Serum anti-Mullerian hormone (AMH), estradiol (E2), inhibin B, LH and FSH were immunoassayed in 31 women with FHA and in 30 healthy women in early follicular phase. The ovarian antral follicle number (FN) was determined within two distinct diameter ranges (2-5 and 6-9 mm) by ultrasound in real time, the same day as the blood sampling. The 2-5 mm FN was similar between the two groups, while the 6-9 mm FN was significantly less in FHA than in controls, in relation with lower serum FSH levels (r=0.428; P<0.024). Nine (29%) FHA patients had a low serum basal FSH level (i.e. <4.5 IU/l, 5th percentile of control values). In the 22 (71%) patients with apparently normal FSH, the mean 6-9 mm FN was similar to controls. However, in this sub-group, the mean AMH serum level and the AMH:2-5 mm FN ratio were significantly higher and the mean inhibin B serum level was significantly lower than in controls. No significant relationship was found between the serum LH levels and the FN, AMH or inhibin B values. Only a minority of patients with FHA have a low serum basal FSH level, and we show that this is associated with fewer 6-9 mm follicles at the ovarian level. Despite a normal serum FSH level and 6-9 mm FN in the majority of patients with FHA, the functional follicle markers are abnormal. This suggests that the FSH action on the ovary is incomplete and is not properly reflected by its serum level nor by FN at ultrasound.

Synergy ofl-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise

We investigated the ability of exercise, a multipathway, potent, physiological stimulus for GH release, to alter the synergistic interaction of L-arginine (A) and GH-related peptide (GHRP)-2 (G) observed at rest and the ability of gender to further modulate this putative interaction. Subjects (9 men and 9 early follicular phase women) completed 30 min of constant load aerobic exercise in combination with intravenous infusions of saline (S), A (30 g over 30 min), G (1 microg/kg bolus), or both (AG) in separate study sessions in randomly assigned order. Measures of GH release were logarithmically transformed for statistical analysis. Similar to rest, exercise maintained the rank order (AG > G > A > S) of effective stimulation of GH release for the key response measures in men or women, a gender disparity in the time to reach the maximal serum GH concentration, the calculated endogenous GH half-life, and the observed effect of preinfusion (basal) serum GH concentrations on determining secretagogue responsiveness. Exercise potentiated the individual stimulatory actions of A and G, while blunting the relative magnitude of the synergistic (supra-additive) interaction observed at rest. We infer from the present data that 1) exercise is likely to induce release of both GHRH and somatostatin, 2) L-arginine may facilitate the effect of exercise by limiting somatostatin release, 3) GHRP-2 could further enhance the stimulatory impact of exercise by opposing central actions of somatostatin and/or heightening endogenous GHRH release, and 4) gender strongly controls the relative but not absolute magnitude of A/G synergy both at rest and after exercise.

Thyroid function in early pregnancy I: Thyroid-stimulating hormone response to thyrotropin-releasing hormone

Maternal thyroid function in pregnancy is influenced by many factors. This study was undertaken to clarify the mechanism of thyroid regulation in the first trimester of normal pregnancy. We performed the thyrotropin-releasing hormone (TRH) test in eight women in the first trimester (week 6-9) of pregnancy and ten normal women in early follicular phase. Basal plasma levels of free triiodothyronine and free thyroxine were within the normal range in both groups, whereas thyroid-stimulating hormone (TSH) was at the lower limit of the normal range in pregnant women. TRH stimulation evoked a TSH response with a peak of 14.1 ± 1.2 mIU/ml at 30 min. In control subjects TSH increased in response to TRH with a peak of 7.4 ± 1.1 mIU/ml at 30 min. Statistical analysis with Student's t test revealed significantly higher TSH levels (p < 0.01) in pregnant women.The most striking finding was the enhanced responsiveness of TSH to TRH stimulation while the thyroid hormones, free triiodothyronine (fT3) and free thyroxine (fT4), remained in the normal range. This response was similar to that observed in central hypothyroidism. These results suggest that the reduction in maternal pituitary TSH levels is due to human chorionic gonadotropin (hCG) inhibition of TRH secretion.

Ultrasound assessment of ovarian stroma hypertrophy in hyperandrogenism and ovulation disorders: visual analysis versus computerized quantification

To extend our previous findings on the diagnostic validity of ovarian stroma hypertrophy in women with hyperandrogenic and/or menstrual disorders. Transvaginal ultrasonography was performed in 69 patients complaining of hyperandrogenism and/or menstrual disorders and in 48 normal ovulatory women in early follicular phase. To check the validity of stroma assessment by visual analysis, we used computer-assisted analysis, which allowed selective measurement of the stromal area on a longitudinal ovarian cut. Sensitivity and specificity of each method were estimated by using the normative data from the control group. Stromal area was considered to be increased using visual analysis and computer-assisted analysis in 74% and 61% patients, respectively. Specificity of this sign was 84% and 96% by visual analysis and computer-assisted analysis, respectively. In patients, the increase in stromal area correlated very significantly with the one of total ovarian area, whose upper normal limit was 5.5 cm2 per ovary. Visual assessment of stroma may be misleading in some cases, with the risk of overestimating its hypertrophy. An increased total ovarian area > 5.5 cm2 (which can easily be detected by carefully shaping a strict longitudinal ovarian cut) has the same diagnostic value as an increased stromal area by computerized measurement.

The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation.

Alprazolam, a benzodiazepine derivative, stimulates specific gamma-aminobutyric acidA receptors and has been found to inhibit CRH activity in the brain. This study examined the effect of alprazolam on serum cortisol and LH pulsatility in six women in the early follicular phase (EFP), six women in the midluteal phase (MLP), and six women with stress-related anovulation (SRA) of normal weight, but with a previous history of anorexia nervosa. Subjects were given alprazolam (2 mg, orally) or an identical placebo capsule at 0900 h, and blood samples were collected through an indwelling venous catheter every 10 min for 8 h in the SRA women and 10 h in EFP and MLP women. Women with SRA were also given clomiphene (100 mg/day) for 5 days before a further 8-h blood sampling session. As expected, there was a diurnal decline in serum levels of cortisol, which was significantly less in women with SRA (55 +/- 4%) than those in both EFP (76 +/- 4%) and MLP women (75 +/- 3%; P < 0.005). The food-related rise of cortisol that follows lunch in normal women was absent in women with SRA. Alprazolam accentuated the decline in serum cortisol, and in all three groups, the mean serum cortisol level after alprazolam treatment was significantly less (P < 0.05) than that after placebo. In SRA women, alprazolam restored visible LH pulses in all women and increased the mean LH pulse frequency (P < 0.02) and pulse amplitude (P < 0.05). This was associated with an increase in mean serum LH from 1.3 +/- 0.3 to 3.0 +/- 0.06 IU/L (P < 0.02). In EFP women, alprazolam reduced the frequency of LH pulsatility from a mean of 5.8 +/- 0.7 to 3.2 +/- 0.5 pulses/10 h (P < 0.02) and increased the mean pulse amplitude from 2.4 +/- 0.5 to 5.0 +/- 1.1 IU/L (P < 0.0005). Alprazolam had no significant effect on LH pulsatility or amplitude in MLP women. To explain this variation in response to alprazolam, we propose that alprazolam accelerates the GnRH pacemaker in SRA women by inhibiting excessive CRH activity, which blocks the GnRH pacemaker in these women. In normal women, we hypothesize that tonic inhibition of the GnRH pacemaker by CRH is minimal, and the reduced pulsatility of LH after alprazolam treatment in EFP women results from inhibition of stimulatory noradrenergic neurons. In MLP women, we propose that preexisting opioid inhibition of noradrenergic neurons by progesterone blocks this effect of alprazolam.

Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women.

Whereas the nocturnal slowing of the LH pulse frequencies in the early follicular phase (EFP) of the menstrual cycle may be attributed to a sleep-associated increase in opioidergic activity, the concomitant augmentation of LH pulse amplitudes remains unexplained. We reasoned whether alterations in the pituitary gonadotropin responsiveness during the 24-hour rest-activity cycle may account for these enhanced LH pulse amplitudes during sleep. Accordingly, 12 EFP women (cycle days 3-5) were studied on 2 consecutive days during three occasions: a day time between 1000 and 1400 h (day studies), at night between 2200 and 0200 h, while the women were awake (night studies), and finally, during identical night hours, while the women were asleep (sleep studies). At all occasions, blood was collected at 10-min intervals for 4 h, while GnRH (25 micrograms) was administered twice within 2 h. During the day studies, prompt and sustained LH and FSH releases were noted in response to the first and second GnRH stimulations. However, the LH and FSH release after both the first and second GnRH challenges was markedly (P < 0.01) blunted during the night studies. By contrast, this decrease in LH, but not FSH response during the night was completely prevented, when GnRH was administered during sleep. Independent of the time at which GnRH had been administered, the second GnRH stimulations provoked much greater (P < 0.05 or less) LH and FSH releases than the first. Thus, a marked attenuation of the gonadotroph responsiveness is observed in EFP women during the night, and nocturnal sleep may eliminate this decline. Further, the priming actions on the gonadotrophs by repetitive GnRH stimulations are unaffected by the time of GnRH administrations. Collectively, these observations permit us to infer that the increased LH pulse amplitudes observed during sleep in EFP women may not be attributed to increased pituitary responsiveness.

Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women

Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women

Pulsatile growth hormone release in normal women during the menstrual cycle.

We sought to characterize pulsatile growth hormone (GH) release in normal women during the menstrual cycle and to document possible relationships between such characteristics and concentrations of 17 beta-oestradiol and progesterone. Fifteen women with ostensibly normal menstrual function were studied during the early follicular phase, 15 during the late follicular phase and 15 during the mid-luteal phase of the menstrual cycle. The phase of the menstrual cycle having been documented, blood samples were obtained from each woman every 10 minutes for 24 hours. Serum GH was measured in each sample by immunoradiometric assay. Pulsatile GH release was appraised utilizing the objective, statistically-based pulse detection algorithm Cluster. The mean (+/- SEM) integrated serum GH concentration (mU/l min) in late follicular phase women (5335 +/- 848) was higher than that observed in early follicular phase women (3156 +/- 322; P = 0.032). The integrated GH concentration calculated for mid-luteal phase women (3853 +/- 788) was intermediate between but not statistically different from that observed in early follicular (P = 0.48) and late follicular (P = 0.14) phase women. No differences in GH pulse frequency (pulses/24 hours) were found among early follicular (8.27 +/- 0.55), late follicular (7.93 +/- 0.91) or mid-luteal (8.47 +/- 0.66) phase women. Mean maximal GH pulse amplitude (mU/l) was higher in late follicular phase (8.93 +/- 1.00) than early follicular phase (5.74 +/- 0.67; P = 0.008) and mid-luteal phase (5.76 +/- 0.74; P = 0.008) women. Similarly, incremental GH pulse amplitude (mU/l) was higher in late follicular phase (7.33 +/- 0.83) than early follicular phase (4.68 +/- 0.58; P = 0.005) and mid-luteal phase (4.36 +/- 0.39; P = 0.002) women. No differences in mean pulse widths or in the interpeak valley mean GH concentrations were found among the groups. Multiple regression of each pulse parameter against serum concentrations of testosterone, 17 beta-oestradiol and progesterone revealed a significant (P = 0.045) positive correlation between maximum GH pulse amplitude and oestradiol and a significant (P = 0.04) negative correlation between maximal GH pulse amplitude and progesterone (r = 0.41). These results suggest that late follicular phase concentrations of oestradiol may enhance circulating GH via an amplitude-modulated rather than a frequency-modulated effect on the endogenous GH pulse. Progesterone may blunt this oestrogen-associated effect, thus resulting in the observed mid-luteal phase concentrations of GH. Whether these gonadal hormones act primarily at the hypothalamus and/or anterior pituitary gland remains to be clarified, but the present observations indicate that pulsatile GH release throughout the normal menstrual cycle is significantly amplitude regulated.

Differential Release of Prolactin Variants in Postpartum and Early Follicular Phase Women*

Several molecular forms of immunoreactive human (h) PRL with differences in biological activities have been described. To investigate these differences in PRL secretion, we have characterized the molecular forms of circulating PRL in postpartum women during breastfeeding (n = 5) and sleep (n = 5) and in eumenorrheic women with galactorrhea (n = 5) after TRH stimulation (n = 4), metaclopramide infusion (n = 5), and morphine administration (n = 2). All provocative testing in eumenorrheic women were carried out during the early follicular phase of the menstrual cycle (days 1-5). PRL variants were identified and semiquantitated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by immunoblotting and autoradiography. Mean basal levels of PRL were significantly elevated in nursing women (P less than 0.01) compared to those in nonlactating postpartum women and women with galactorrhea. The relative proportions of PRL variants [glycosylated PRL with an apparent mol wt of 25K and a nonglycosylated species (hPRL) with an apparent mol wt of 23 K] were similar for all three groups. A third immunoreactive PRL variant with an apparent mol wt of 21K was identified in nonlactating postpartum women. With breastfeeding or sleep, PRL concentrations increased more than 4-fold and were accompanied by a shift toward the lower mol wt, nonglycosylated species. In response to TRH (200 micrograms, iv), PRL levels increased by 493 +/- 86% (mean +/- SE) over basal levels. This acute release of PRL was positively correlated (r = 0.06074; P less than 0.001) with a significant increase in secretion of the hPRL species (P less than 0.05). During metaclopramide infusion, a similar increment in hPRL was observed during acute PRL release. Administration of the opiate agonist morphine was associated with a small increment in PRL release and did not alter the proportions of PRL variants in the circulation. Because glycosylation is a posttranslational step in the processing of PRL, our studies suggest that the acute release of PRL in response to physiological and pharmacological secretagogues may reflect the output of more recently synthesized PRL from the pituitary. The physiological role of the 21K PRL species remains to be determined.

RELATIVE CHANGES IN LH PULSATILITY DURING THE MENSTRUAL CYCLE: USING DATA FROM HYPOGONADAL WOMEN AS A REFERENCE POINT

The basic premise of this study is that the GnRH-LH pulsatile activity, particularly its frequency characteristics, constitutes, in the absence of any considerable ovarian feedback, the intrinsic rhythm of the hypothalamic-pituitary unit at its maximal rate. Thus, LH pulse attributes determined in postpubertal hypogonadal subjects may be used as a reference in assessing the degree of influence exerted by endocrine factors that modulate GnRH-LH pulses. Accordingly, serum LH levels were determined in samples obtained at 15-min intervals for 24 h in 20 hypogonadal women: 13 postmenopausal women (PMW) and seven women with premature ovarian failure (POF). Similar measurements were performed in 60 normally cycling women: 25 in the early follicular phase (EFP), 13 in the late follicular phase (LFP), seven at midcycle surge (LH surge) and 15 in the midluteal phase (MLP). Significant pulses were identified by the cluster algorithm utilizing factors appropriate for 24 h data series of a sampling frequency of 15-min intervals. The results show a 24-h mean (+/- SE) LH pulse frequency of 78.2 +/- 2.8 and 85.5 +/- 2.4 min per pulse for young (POF) and older (PMW) hypogonadal women, respectively. During the follicular phase of the cycle, the LH pulse frequency is not significantly different from that of hypogonadal women, but there is a significant (P less than 0.05) increase from early to late follicular phases (95.4 +/- 3.3 vs 78.8 +/- 2.2 min per pulse). However, when the sleep periods are excluded from the 24-h data series because of the associated decrease of LH pulse frequency in EFP women, the resulting pulse frequencies are almost identical for EFP, LFP and PMW. An elevation beyond the basic pulse rhythm determined in PMW or POF is not observed in any phase of the menstrual cycle studied, including the midcycle surge. The decrease in LH pulse frequency during the luteal phase of the cycle (151.8 +/- 8.0 min per pulse, P less than 0.001 vs hypogonadal women) beyond the reference pulse frequency of hypogonadal women is unequivocal. By contrast, the pulse amplitude varies markedly among the groups with the largest found in POF (36.6 +/- 4.5 IU/l). It follows, in descending order, PMW (22.7 +/- 3.1 IU/l), midcycle surge (17.3 +/- 2.8 IU/l), MLP women (7.0 +/- 1.3 IU/l) and the EFP (4.9 +/- 0.3 IU/l) and LFP (4.0 +/- 0.4 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin-releasing hormone pacemaker sensitivity to negative feedback inhibition by estradiol in women with hypothalamic amenorrhea

To better understand the pathophysiology of hypothalamic amenorrhea (HA), the frequency of luteinizing hormone (LH) pulsatility and the LH response to gonadotropin-releasing hormone (GnRH) was assessed before and after clomiphene citrate (CC) in 18 women with HA and 10 normal women in the early follicular phase (EFP). The HA women showed a greater acceleration of LH pulsatility after CC than EFP women but there was a decrease in their LH response to GnRH. Naloxone caused an increase in LH pulsatility in HA but not EFP women, although this effect was less than that seen with CC. We conclude that, in HA women, the GnRH pacemaker, but not the pituitary, is inhibited by increased sensitivity to the negative feedback effect of estradiol and increased opiate tone.

Gonadotropin-releasing hormone pacemaker sensitivity to negative feedback inhibition by estradiol in women with hypothalamic amenorrhea

To better understand the pathophysiology of hypothalamic amenorrhea (HA), the frequency of luteinizing hormone (LH) pulsatility and the LH response to gonadotropin-releasing hormone (GnRH) was assessed before and after clomiphene citrate (CC) in 18 women with HA and 10 normal women in the early follicular phase (EFP). The HA women showed a greater acceleration of LH pulsatility after CC than EFP women but there was a decrease in their LH response to GnRH. Naloxone caused an increase in LH pulsatility in HA but not EFP women, although this effect was less than that seen with CC. We conclude that, in HA women, the GnRH pacemaker, but not the pituitary, is inhibited by increased sensitivity to the negative feedback effect of estradiol and increased opiate tone.

Effects of acute hyperprolactinemia on LH pulsatile secretion in hypogonadal and early follicular phase women

To investigate the effects of acute hyperprolactinemia on the 24 h LH pulsatile pattern, 11 women in the early follicular phase (EF, days 3 and 4) and 8 postmenopausal women (PMW) were studied before and during administration of metoclopramide, a dopamine receptor antagonist. Sequential 24 h infusions of either metoclopramide (MCP, 30 μg/kg/h) or normal saline were conducted and pulsatile LH activity assessed for 48 hrs. In both EF women and PMW, a prompt (within 90 min, p<0.001) and sustained (> 45 μg/L, p<0.001) released of PRL was induced by MCP infusions. MCP-induced hyperprolactinemia failed to modify the LH pulsatile activity in both EF women and PMW. These observations suggest that acute hyperprolactinemia due to dopaminergic blockade has no discernible effect on LH pulsatility and that the reduced LH pulse frequency observed in association with endogenous hyperprolactinemia may result from different neuroendocrine mechanism(s) and/or is time dependent.

Effects of Dopaminergic Blockade on the Sleep-Associated Changes of Luteinizing Hormone Pulsatility in Early Follicular Phase Women

To investigate the dopaminergic role in the sleep-associated changes of luteinizing hormone (LH) pulsatile pattern, 11 normal cycling women were studied in the early follicular phase (EF, days 3 and 4) of their cycles before and after the administration of metoclopramide (MCP), a dopamine receptor antagonist. Twenty-four-hour infusions of either saline (NaCl 150 mmol/1-50 ml/h) or metoclopramide (MCP, 30 micrograms/kg/h) were conducted in a random sequence. Pulsatile LH activities were assessed in blood samples obtained at 15-min intervals for 48 h. Sleep was electrophysiologically confirmed by EEG during night hours (23.00-07.00 h). Significant sleep-associated decreases in LH pulse frequency (p less than 0.05) and mean LH serum levels (p less than 0.001) with a concurrent increase in LH pulse amplitude (p less than 0.01) were observed during the saline control studies. MCP infusion failed to significantly modify the LH pulsatile activity during either the wake or sleep periods. In particular, it did not prevent the changes in LH pulsatility during sleep. This observation suggests that a dopaminergic mechanism does not critically contribute to the sleep-related changes in LH pulsatile activity in women during the early follicular phase.

Prolactin-releasing action of gonadotropin-releasing hormone in hypogonadal women.

To gain insight into the PRL-releasing effect of GnRH, serum PRL and gonadotropin responses to a 10-microgram iv bolus dose of exogenous GnRH were studied in hypergonadotropic hypogonadal women (HHW) and patients with functional hypothalamic amenorrhea (FHA). The results were compared with those obtained in normal cycling women during the early follicular phase of the cycle. GnRH induced a significant increase in PRL levels (P less than 0.001) in HHW compared to early follicular phase women, in whom no significant response occurred. In HHW, the maximal PRL percent increment was positively correlated with the ratio of the maximal percent increments of FSH and LH (r = 0.93). GnRH induced a significant increase in PRL levels in every FHA patient, but in four of them (high PRL responders), the PRL response was at least 5-fold greater than in the other six (low PRL responders). The clinical profiles, basal hormone concentrations, and LH responses to GnRH were similar in these two groups of FHA patients, but the FSH response to GnRH was greater (P less than 0.05) in the high PRL responders. The maximal percent increment of PRL was also positively correlated with the maximal percent increment of FSH (r = 0.76; P = 0.01). These data demonstrate that in these two hypogonadal models, the PRL response to exogenous GnRH corresponds to the FSH response and suggests that GnRH-stimulated PRL release may be mediated by a paracrine effect between FSH-enriched gonadotrophs and lactotrophs.

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.

The effect of physiological changes in ovarian steroids on the prolactin response to gonadotrophin releasing factor.

This study was designed to assess the effect of an altered level of serum oestrogen and progesterone on the prolactin (PRL) response to gonadotrophin releasing hormone (GnRH). Six normal women were studied in the early follicular phase and the mid-luteal phase of one cycle and five menopausal women were studied before and after treatment with progesterone. Blood samples were collected at 15 min intervals for 6 h after a basal collection period of 30 min. Intravenous boluses of GnRH (1 microgram, 10 micrograms and 50 micrograms) were given at 0, 2 and 4 h. Basal samples were assayed for 17 beta-oestradiol (E2), oestrone (E1) and progesterone (P); LH, FSH and PRL were measured in all samples. Serum PRL was significantly elevated in all groups after 10 micrograms of GnRH with maximum increments (+/- SEM) ranging from 3.9 +/- 1.3 micrograms/l in early follicular phase women to 14.7 +/- 4.7 micrograms/l in progesterone-treated menopausal women. The PRL response to GnRH was significantly greater in the luteal phase and in menopausal women compared to early follicular phase women. There was a significant correlation between the maximum PRL response and the maximum LH response to GnRH in all the women studied (r = 0.7; P less than 0.01). A significant correlation was also found between the maximum PRL response and the basal serum oestrogen concentration in the normal cycling women (r = 0.8; P less than 0.01), but not when the menopausal women were included in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-lipotrophin and beta-endorphin plasma levels during pregnancy.

beta-lipotrophin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were measured by radioimmunoassay after glass powder extraction and Sephadex G-75 column chromatography in plasma samples from controls (ten healthy males and twenty-six young women in early follicular phase), from eighty-two pregnant women in weeks 9-40 after their last menstrual period, from nine women just after delivery and the cord blood of their neonates, in fifteen mixed cord blood samples and in seven amniotic fluid samples obtained by amniocentesis. No sex differences were found in beta-LPH (120.6 +/- 8.5 pg/ml) or beta-EP (31.1 +/- 2.4 pg/ml) plasma levels or in their molar ratio (1.34 +/- 0.09) (MR). beta-LPH plasma levels increased in early pregnancy (13-16 weeks) (185.0 +/- 27.1 pg/ml) and remained high until weeks 21-24, then declining to levels similar to those of controls. beta-EP plasma levels were significantly depressed in weeks 9-12 (20.7 +/- 5.3 pg/ml), subsequently increasing to a maximum at weeks 36-37 (42.7 +/- 6.8 pg/ml). beta-LPH/beta-EP molar ratio was about double normal in early pregnancy and decreased to normal in the second half. The present data indicate that beta-LPH and beta-EP present different patterns throughout pregnancy and that beta-EP levels increase progressively, reaching the highest concentrations at term. At delivery, both beta-LPH and beta-EP showed maximum values (beta-LPH: 230.2 +/- 20.4 pg/ml; beta-EP: 78.0 +/- 7.4 pg/ml) and a MR of 1.02 +/- 0.10 indicating that stressful situations, such as labour, stimulate a simultaneous rise in beta-LPH and beta-EP plasma levels. Cord blood specimens showed a wide range of values (beta-LPH:75-347 pg/ml; beta-EP: 16-287 pg/ml) with a MR of 1.21 +/- 0.14. Amniotic fluid samples obtained late in the third trimester of pregnancy were characterized by beta-LPH levels of 119.4 +/- 26.4 pg/ml and beta-EP levels of 29.6 +/- 7.5 pg/ml.

Ovarian steroidogenesis in Japanese patients with polycystic ovary syndrome.

Gonadotropin and steroid hormone levels in both peripheral and ovarian venous blood were measured in samples obtained from 20 Japanese patients with polycystic ovary syndrome (PCOs) and 10 normal women in early follicular phase (normal women) by radioimmunoassay. The change in the amount of steroid hormone following intravenous human menopausal gonadotropin (HMG) or dexamethasone administration was investigated. The mean concentration in patients with PCOs was significantly higher than the concentrations found in normal women for LH (p less than 0.001), but not for FSH in peripheral blood. Significantly elevated ovarian venous steroid hormone levels in PCOs were found for 17 alpha-hydroxypregnenolone (p less than 0.05), progesterone (p less than 0.05), 17 alpha-hydroxyprogesterone (p less than 0.01), 4 delta-androstenedione (p less 0.01), testosterone (p less than 0.01), estrone (p less than 0.01) and estradiol (p less than 0.05), but not for dehydroepiandrosterone-sulfate (DHEAS). The ovarian dehydroepiandrosterone (DHEA) level was slightly elevated in PCOs. The concentration of ovarian 4 delta-androstenedione in PCOs reached twelve times as much as that in normal women. After the administration of HMG, all of the ovarian venus steroid hormone levels were elevated slightly and without significance in the short observation time for 10 min. The DHEAS level was suppressed while the ovarian DHEA level remained high in PCOs following dexamethasone administration. These findings seem to indicate there is no adrenal involvement and no adrenal-like component in the ovary of PCOs, and no evidence of 3 beta-hydroxysteroid dehydrogenase and/or aromatase deficiency in this study. The increase in the steroid hormone secretion in PCOs is explained by the increase in ovarian production in polycystic enlarged ovaries.