Patterns of luteinizing and follicle-stimulating hormone pulsatility in menopausal women: correlation with plasma testosterone level and vasomotor instability episodes.

OBJECTIVE: The purpose of this study was to test the hypothesis that subtle differences among postmenopausal women can be detected by careful analysis of plasma luteinizing hormone and follicle-stimulating hormone pulses. STUDY DESIGN: Twelve postmenopausal women not receiving estrogen therapy were admitted for continuous blood withdrawal at the rate of 1 ml/min. Aliquots of 3 ml of pooled blood were collected every 3 minutes for 3 hours for the measurement of plasma luteinizing hormone and follicle-stimulating hormone. Estradiol, estrone, free testosterone, androstenedione, and dihydrotestosterone were measured from pooled specimens. Concomitantly, continuous recordings of peripheral blood flow and peripheral temperature from the opposite arm were obtained to detect vasomotor instability episodes. RESULTS: Analysis of gonadotropin pulses revealed a single pattern of plasma follicle-stimulating hormone but two distinct patterns of luteinizing hormone frequency and amplitude. One group of six women had a low mean (+/- SEM) interpulse interval frequency of 0.8 +/- 0.26 (p < 0.005) and a high mean amplitude of 18.4 +/- 1.8 IU/L (p < 0.05). The second group of six women had a high mean interpulse interval frequency of 3.5 +/- 0.34 and a low mean amplitude of 12.2 +/- 1.8 IU/L luteinizing hormone pulses. Women with this pattern had more inter-vasomotor instability episode intervals (3.5 +/- 1.6) than did women with low frequency and high amplitude (1.3 +/- 0.5, p < 0.001). Women with low frequency and high amplitude pulses had higher plasma levels of estrone (266 +/- 33 nmol/L), testosterone (2.3 +/- 0.7 mmol/L), and free testosterone (8.0 +/- 0.1 pmol/L, p < 0.05). CONCLUSION: There are subgroups of postmenopausal women with different patterns of luteinizing hormone pulsatility. This difference can be explained by higher steroid levels in women with low frequency and high amplitude pulses.

Absence of a dose-response effect of leuprolide acetate on leiomyomata uteri size.

OBJECTIVE: To evaluate the effects of two different doses (3.75 mg versus 7.5 mg) of leuprolide acetate (LA, Lupron; Tap Pharmaceuticals, Deerfield, IL) on myoma size, blood loss during myomectomy, on magnetic resonance imaging (MRI) signal quality, and histopathologic changes in women requiring myomectomy. DESIGN: Prospective, nonrandomized, sequential study. SETTING: Urban center teaching hospital. PATIENTS: Twenty-eight women with uterine leiomyomata requiring myomectomy. INTERVENTIONS: Nine women were entered as controls (group 1), 10 women received 3.75 mg IM (group 2), and 9 women received 7.5 mg IM of LA (group 3) each for 3 months before myomectomy. RESULTS: The uterine size and hematocrit among the three groups of patients before treatment was not significantly different. A significant reduction of 34.5% and 34.6% in myomata size was seen in groups 2 and 3. The estimated average blood loss at myomectomy was 745 +/- 101 mL, 615 +/- 177 mL, and 722 +/- 192 mL in groups 1, 2, and 3, respectively. The postoperative hematocrit was not different among the three groups (29.8% +/- 0.9%, 30.4% +/- 1.6%, and 29.8% +/- 1.2%). There was no evidence of cytologic atypia, increased mitosis, or change in fibrosis in LA-treated women. There were no characteristic MRI or histologic changes seen after LA treatment as compared with controls. CONCLUSIONS: The results of this study have demonstrated that both doses of LA (3.75 and 7.5 mg) can induce a significant and similar degree of size reduction in myomas and that neither dose of LA aided in the reduction of blood loss at myomectomy and therefore should not be used routinely.

Transcervical fallopian tube catheterization and recanalization for proximal tubal obstruction.

OBJECTIVE: To evaluate further the safety and efficacy of selective ostial salpingography combined with transcervical wire recanalization for the diagnosis and treatment of proximal tubal obstruction. DESIGN: Prospective study. SETTING: Division of Reproductive Endocrinology and Department of Radiology at Harbor-University of California Los Angeles (UCLA) Medical Center, a tertiary care academic institution. PATIENTS: Twenty-eight infertile patients diagnosed with proximal tubal obstruction by hysterosalpingogram (HSG) or by chromopertubation at laparoscopy (total of 46 obstructed tubes). INTERVENTIONS: After antibiotic prophylaxis and IV analgesia a conventional HSG was performed. If proximal tubal obstruction was confirmed, selective salpingography was done under fluoroscopic guidance. If proximal tubal obstruction was still present, wire recanalization using a new prototype cannula was then performed. If recanalization was successful, contrast media was injected to confirm tubal patency. MAIN OUTCOME MEASURES: Proximal tubal patency, complete tubal patency, pregnancies. RESULTS: Eleven of 46 tubes (23.9%) were patent by HSG. Ostial salpingography of the remaining 35 tubes revealed 6 patent tubes (13%). Nine of the 29 obstructed tubes (31%) had successful wire recanalization, and 8 of these were patent distally. There were 4 intrauterine pregnancies (IUPs) and 1 ectopic pregnancy after recanalization and 2 IUPs after ostial salpingography. CONCLUSION: Selective salpingography should be considered at the time of an HSG showing proximal tubal obstruction. If indicated, wire recanalization can also be attempted. Selective ostial salpingography combined with wire recanalization is a safe and effective procedure for the diagnosis and treatment of PTO.

Reliability of transvaginal ultrasound in detecting first trimester pregnancy abnormalities.

OBJECTIVE: To evaluate the reliability of transvaginal ultrasound (US) and human chorionic gonadotropin (hCG) levels in detecting early abnormalities and predicting outcome of pregnancy. PATIENTS: One hundred thirty-two patients were studied, of which 113 had an intrauterine pregnancy and 19 had an ectopic pregnancy (EP). RESULTS: In 78 with singleton normal pregnancies, US revealed a normal crown-rump length, heart motion, and hCG levels between 1,000 to 107,000 mIU/mL. Of 16 patients with small crown-rump length, heart motion present, and normal hCG levels, 6 aborted and 10 reached term. Thus, 6 of 84 (7.14%) singleton with fetal heart motion aborted. Thirteen with small crown-rump and absent heart motion also aborted. All 8 with an empty gestational sac aborted. In 8, transvaginal US detected four twins, two triplets, and two quadruplets, whereas hCG was not discriminative. Transvaginal US revealed an empty uterus in 19 patients with an EP, whereas serum hCG varied between 37 and 10,500 mIU/mL. CONCLUSION: A fetal crown-rump length compatible with gestational age and fetal heart motion seen by transvaginal US can predict a term pregnancy in greater than 90% of patients.

Effect of bromocriptine on sperm function in vitro and in vivo.

Vaginal bromocriptine is an effective method for the treatment of hyperprolactinemia, but it is unknown whether bromocriptine applied vaginally can interfere with sperm function. Thus, we sought to determine the effects in vitro and in vivo on sperm directly exposed to bromocriptine. Ten semen specimens from normal donors were diluted with Ham's F-10 medium and incubated with 0, 0.01, 0.1, and 1.0 mmol/L bromocriptine solution or diluent without bromocriptine. Computerized semen analysis revealed a 31% decrease in sperm motility, a 24% decrease in sperm average path velocity, and a 33% decrease in sperm average straight line velocity only using 1.0 mmol/L of bromocriptine (P less than .05). In addition, eight women with hyperprolactinemia and infertility who were receiving vaginal bromocriptine consented to a postcoital test. Five became pregnant and delivered normal infants. Four of the five women who had a postcoital test had six, eight, ten, and ten motile sperm per high-power field and one had one to two motile sperm per high-power field. Because sperm function was preserved enough to result in fertilization and term pregnancy, the clinical importance of the in vitro findings is probably minimal and it can be concluded that vaginal bromocriptine can be used in women with infertility due to hyperprolactinemia.

Biochemical and biophysical indices of follicular development in spontaneous and stimulated ovulatory cycles.

This study was designed to evaluate the correlation between the follicular biophysical and biochemical indicators in spontaneous (N = 11) and stimulated (N = 110) ovulatory cycles. Ovulation was induced with clomiphene citrate in 14 cycles, gonadotropin-releasing hormone (GnRH) in 12 cycles, and human menopausal gonadotropins in 84 cycles. Patients were studied daily, starting on day 10, until sonographic verification of ovulation. Each woman had serum estradiol (E2) and LH measured daily and progesterone measured only 7 days after ovulation. In addition, the ovaries were imaged transvaginally daily and the two largest follicular diameters, volumes, cross-sectional areas, and circumferences were measured in all follicles 10 mm or larger in diameter. Ultrasonographic measurements of follicles from clomiphene-stimulated cycles were significantly larger than those from spontaneous, GnRH-, and human menopausal gonadotropins-stimulated cycles (P less than .05). Serum E2 and progesterone secretion in human menopausal gonadotropins- and clomiphene-stimulated cycles were significantly higher than in spontaneous and GnRH-stimulated cycles (P less than .01). Women treated with human menopausal gonadotropins developed significantly more follicles than with any other treatment (P less than .05). Correlation analysis indicated that biophysical variables alone (follicular diameter, volume, cross-sectional area, or circumference) were good indicators of normal follicular development and predicted the mid-cycle LH surge in spontaneous (r = 0.81, P less than .001), GnRH- (r = 0.78, P less than .001), and clomiphene citrate-stimulated cycles (r = 0.83, P less than .001). However, in human menopausal gonadotropins-stimulated cycles, both serum E2 levels and ultrasonographic evaluation were necessary to decide the best time for hCG administration (r = 0.55, P less than .001).

Computed tomography versus magnetic resonance imaging for the evaluation of suspected pituitary adenomas.

The purpose of this study was to evaluate and compare thin-section magnetic resonance imaging (MRI) and high-resolution computed tomography (CT) in patients with suspected pituitary adenomas. Twenty-two patients (19 women and three men) with hyperprolactinemia (N = 16), increased growth hormone secretion (N = 2), increased corticotropin secretion (N = 1), and nonsecreting adenomas (N = 3) were studied with both contrast-enhanced, high-resolution CT scanning and thin-section MRI. Contrast-enhanced examinations consisted of contiguous 1.5-mm coronal sections during contrast infusion. The MRI examinations consisted of spin-echo T1- and T2-weighted sequences with a 2.5-3.0-mm slice thickness on the coronal and sagittal planes. Fourteen women had similar findings on CT and MRI (four macroadenomas, six microadenomas, one wide stalk, two empty sellas, and one normal study). The remaining eight subjects had conflicting results: CT findings were compatible with a microadenoma in all eight patients, whereas MRI detected one enlarged pituitary, two empty sellas (one with prolapse of the optic chiasm) without evidence of adenoma, and five normal examinations. Thus, both studies detected macroadenomas accurately, but CT was frequently unable to diagnose correctly an empty sella. Because patients with possible microadenomas were not submitted to surgery, the accuracy of either radiologic method cannot be assessed at this time. However, we suggest that MRI is superior to CT because of its inherently greater soft-tissue contrast, which allows clear visualization of the optic chiasm, optic nerves, cavernous sinuses, and carotid arteries.

Effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia.

Treatment of hyperprolactinemia with oral bromocriptine has been associated with a high incidence of side effects. The authors recently demonstrated that, in normal women, the vaginal route of administration was an effective and safe alternative to oral bromocriptine. To evaluate the effectiveness of vaginal bromocriptine in treating women with hyperprolactinemia, the authors treated 15 hyperprolactinemic women with daily vaginal administration of 2.5 mg tablets of bromocriptine. Serum prolactin (PRL) levels and vital signs were measured daily for 6 days, then weekly for 4 weeks. Gastrointestinal side effects were limited to a single episode of mild nausea, and two cases of transient constipation. In all patients there was a dramatic initial reduction in PRL in response to a single 2.5 mg dose of bromocriptine. In 13 patients PRL levels were maintained within the normal range with daily administration of 2.5 mg, whereas in two patients, PRL levels remained higher than normal despite an increase in bromocriptine dose to 5 mg. These results suggest that short term use of vaginal bromocriptine is a safe and effective method of therapy for hyperprolactinemia.

Vaginal bromocriptine: pharmacology and effect on serum prolactin in normal women.

Oral bromocriptine treatment of hyperprolactinemia is frequently associated with gastrointestinal side effects. To assess the efficacy and safety of an alternate route of treatment, we randomly administered 2.5, 5.0, and 7.5 mg of bromocriptine vaginally to five normal women at 1-week intervals. Plasma bromocriptine and prolactin (PRL) levels were measured hourly for 12 hours, then every 2 hours for 12 hours after each dose. At the end of each study, the vagina was flushed with saline for measurement of residual drug. For comparison of serum PRL levels, six additional women were given 2.5 mg bromocriptine orally. After administration of 2.5, 5.0, and 7.5 mg vaginally, plasma bromocriptine was initially detectable at 5.4 +/- 0.4, 4.4 +/- 0.7, and 3.5 +/- 0.6 hours, respectively. For the same vaginal doses, the mean (+/- SEM) peak plasma levels were 555 +/- 164 pg/mL at 12 +/- 0.6 hours, 702 +/- 252 pg/mL at 11.2 +/- 0.9 hours, and 1055 +/- 220 pg/mL at 10.7 +/- 1.7 hours, respectively. After each dose, there was a slow decline in plasma bromocriptine levels, remaining above 50% of peak values at 24 hours. Less than 1% of the administered drug was recovered from the vagina at 24 hours. The pattern of PRL inhibition with all three doses was similar. The mean plasma PRL level decreased by 7 hours, the maximum PRL decrease (64 +/- 3, 75 +/- 1, and 66 +/- 4% after 2.5, 5.0, and 7.5 mg, respectively) occurring at 11 hours, and the plasma PRL levels changed little during the remaining 13 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of norepinephrine administration upon pituitary hormone secretion in normal men.

This study has investigated the effects of 6.2, 12.5, 25, 50 and 100 ng/kg/min/60 min of NE infused to normal men. Blood samples were obtained every 10 min, before, during and after drug administration for 3 consecutive h. Plasma levels on NE, LH, FSH, PRL, and GH were measured in all samples. The administration of 12.5 ng/kg/min over 60 min of NE induced a significant increase (p less than 0.001) in plasma NE levels (n = 5) from a mean (+/- SE) baseline of 239 +/- 14 ng/L to 706 +/- 54 ng/L which peaked and plateaued at 40 min. The calculated area under the curve was 18562 +/- 3537 ng/L/h of NE and significantly higher (p less than 0.001) than during the h before the infusion (2358 +/- 780 ng/L/h). This increase in plasma NE correlated well with the rise in plasma LH which showed a steady increase from baseline of 7.4 +/- 1.3 mIU/ml to a significant (p less than 0.05) peak of 11 +/- 1.9 mIU/ml at the end of the infusion. Furthermore, analysis of the area under the curve revealed a greater (p less than 0.05) LH release during the NE infusion (180 +/- 18 mIU/ml/h) than before the infusion (92 +/- 17 mIU/ml/h). With the exception of the studies utilizing 12.5 ng/kg/min/60 min, all other doses of NE resulted in no significant and/or consistent changes in plasma concentration of LH, FSH, GH and PRL. Thus, the direct participation of NE in the control of LH secretion in humans seems to occur in a very narrow window.

Early detection of pregnancy with transvaginal ultrasound.

The gestational age and the serum human chorionic gonadotropin (hCG) at which an intrauterine pregnancy can be detected using transvaginal ultrasonography (TVU) is not known. In this study, ten pregnant women were serially scanned with TVU from the time of initial positive pregnancy test, to determine when an intrauterine sac greater than 2 mm, fetal pole greater than 2 mm, and fetal heart motion could be detected. A gestational sac was seen 34.8 +/- 2.2 days from the last menstrual period (LMP), at which time the hCG was 1398 +/- 155 mIU/ml of the International Reference Preparations (IRP) or 914 +/- 106 mIU/ml of the Second International Standard (second IS). A fetal pole was seen 40.3 +/- 3.4 days from the LMP when the hCG was 5113 +/- 298 mIU/ml of the IRP or 3783 +/- 683 mIU/ml of the second IS. Fetal heart motion was detected 46.9 +/- 6.0 days from the LMP when the hCG was 17,208 +/- 3772 mIU/ml of the IRP or 13178 +/- 2898 mIU/ml of the second IS. From these results, it can be concluded that transvaginal ultrasonography can detect an intrauterine gestation earlier than what has been previously reported with transabdominal ultrasonography.

Hyperparathyroidism and hypotestosteronemia of acute renal failure.

Acute and chronic renal failure are associated with a marked reduction in the serum levels of testosterone. The mechanisms underlying this abnormality are unknown. Certain data have implicated the high blood levels of parathyroid hormone (PTH) of uremia in the genesis of the hypotestosteronemia. The effects of 3 days of acute uremia in dogs with intact parathyroid glands and in thyroparathyroidectomized animals on serum testosterone levels and on the calcium content of the hypothalamus, pituitary gland, and the testes were examined. Similar studies were performed in normal dogs treated with parathyroid extract for 3 days. The serum levels of testosterone were significantly (p less than 0.01) reduced, and the calcium levels of hypothalamus, pituitary gland, and testes were significantly (p less than 0.01) increased in the acutely uremic dogs with intact parathyroid glands and in the normal dogs treated with parathyroid extract. Prior parathyroidectomy in the acutely uremic dogs prevented these abnormalities. The results of our study assign an important role for the excess blood levels of PTH in uremia in the genesis of the hypotestosteronemia. The data suggest that the effect of excess PTH on serum testosterone levels may be mediated through the accumulation of calcium in the organs which participate in synthesis and/or release of testosterone.

Follicle-stimulating hormone is the main determinant of follicular recruitment and development in ovulation induction with human menopausal gonadotropin.

The early hormonal changes that lead to follicular maturation and/or hyperstimulation in women requiring ovulation induction with either human menopausal gonadotropin or gonadotropin-releasing hormone have not been elucidated. This study was undertaken to assess the relative contribution of follicle-stimulating hormone and luteinizing hormone to estradiol secretion and follicular maturation in patients receiving human menopausal gonadotropin or gonadotropin-releasing hormone. The study group consisted of 10 women (26 to 38 years of age) with secondary amenorrhea as a result of hypothalamic dysfunction who had failed to ovulate when given clomiphene citrate. The patients were randomly assigned to either human menopausal gonadotropin (n = 5) or gonadotropin-releasing hormone (n = 5) treatment. On day 5 after the onset of induced menses, all women had baseline blood samples obtained at 10-minute intervals for 4 hours. At this time either 150 U of human menopausal gonadotropin or 75 ng/kg of gonadotropin-releasing hormone administered hourly was given, and blood sampling every 10 minutes was continued for an additional 6 hours. Thereafter, patients were evaluated daily until ovulation. A significant and sustained increase in the mean plasma follicle-stimulating hormone level was first measured during the third hour after human menopausal gonadotropin administration (p less than 0.05. The area under the curve of the mean plasma follicle-stimulating hormone value after this initial increase was significantly greater than its baseline (2119 +/- 240 versus 1425 +/- 188 mlU/ml; p less than 0.01). This rise in mean follicle-stimulating hormone level was followed in less than 2 hours by a significant and uniform rise in mean plasma estradiol concentration (p less than 0.05). In contrast, no immediate change in the mean levels of luteinizing hormone, follicle-stimulating hormone, or estradiol occurred after gonadotropin-releasing hormone administration. The mean daily levels of luteinizing hormone were similar in both groups; however, mean daily follicle-stimulating hormone (20.0 +/- 1.1 versus 9.2 +/- 1.4 mlU/ml) and estradiol (1004 +/- 174 versus 495 +/- 83 pg/ml) levels were significantly higher in patients treated with human menopausal gonadotropin than in those treated with gonadotropin-releasing hormone (p less than 0.001 and p less than 0.05, respectively). In addition, only in patients receiving human menopausal gonadotropin was a positive correlation found between mean daily plasma estradiol and follicle-stimulating hormone (r = 0.685, p less than 0.05) levels and between mean daily plasma estradiol and prolactin (r = 0.94, p less than 0.001) levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Longitudinal evaluation of the luteal phase and its transition into the follicular phase.

The precise patterns of LH, FSH, and PRL secretion and their correlation with estradiol (E2) and progesterone (P) secretion during the entire luteal phase have not been elucidated. To analyze in detail the secretory patterns of these hormones we performed 29 consecutive studies in 5 healthy, regularly menstruating women throughout their luteal phase [days 0 (ovulation), 2, 6, 10, and 14] and subsequent early follicular phase (day 2F). During each study plasma LH, FSH, PRL, E2, and P were measured at 10-min intervals for 6 h. Both plasma LH concentrations and LH pulse frequency declined from days 0 to 10 and increased thereafter, whereas LH pulse amplitude continued to decline throughout the luteal and early follicular phases. Plasma FSH concentrations followed a pattern similar to that of LH; however, there was a larger increase in the FSH level on days 14 and 2F. Plasma PRL levels declined initially on day 2 and again on day 14. Regression analysis indicated a positive correlation between LH concentrations and LH pulse frequency (r = 0.715; P less than 0.001) and between PRL and E2 concentrations (r = 0.528; P less than 0.01). A negative correlation was found between plasma P concentrations and both LH concentrations (r = -0.521; P less than 0.01) and LH pulse frequency (r = -0.633; P less than 0.001) and between plasma E2 and FSH concentrations (r = -0.762; P less than 0.001). Thirty-six (65%) PRL pulses and only 11 (39%) FSH pulses coincided with LH pulses. There was no clear pulsatile pattern of secretion of either E2 or P. We conclude that 1) the plasma LH, FSH, PRL, E2, and P concentrations vary markedly throughout the luteal phase; 2) the plasma LH level is largely dependent on the frequency of LH pulses; 3) plasma P decreases plasma LH by reducing the frequency of LH pulses; 4) the remarkable synchrony between PRL pulses and LH pulses implies that their secretion may be regulated by a common neuroendocrine mechanism; and 5) the preferential increase in FSH during the late luteal phase may play an important role in follicular recruitment for the subsequent cycle.

Monitoring techniques to predict and detect ovulation.

This study was designed to evaluate the accuracy of various methods in predicting and detecting ovulation in 14 spontaneous and 17 clomiphene citrate (CC)-induced cycles. From cycle day 11 all subjects (n = 27) were followed with daily transvaginal ultrasound; rapid measurement of serum luteinizing hormone (LH) and estradiol (E2); determination of urinary LH with First Response (Tambrands Inc., Palmer, MA) and Ovustick (Monoclonal Antibodies, Inc., Mountain View, CA) kits; and recording of basal body temperature (BBT). The results demonstrated that transvaginal ultrasound detected ovulation in all cycles. Mean daily serum LH levels were similar in both groups, and peak values of 40 mIU/ml or greater preceded the day of ovulation in all cycles. Serum E2 peak was significantly greater in CC cycles (961 +/- 96 versus 463 +/- 39 pg/ml) (P less than 0.01) and preceded the LH peak in 97% of the cycles. First Response and Ovustick predicted ovulation in 53.3% and 87.5% of the cycles, respectively (P less than 0.01). BBT nadir predicted the day of ovulation in only 10% of cycles. In conclusion, this study revealed that transvaginal ultrasound is an excellent method for detection of ovulation and that Ovustick is a very useful method for prediction of the day of ovulation.

Influence of sequential doses of 5-hydroxytryptophan on prolactin release.

It is known that the administration of serotonin or its precursors induces the release of prolactin. This study was performed (1) to determine the minimal dose of 5-hydroxytryptophan that would produce a consistent and significant prolactin increase and (2) to establish the frequency of 5-hydroxytryptophan administration necessary to induce a persistent prolactin increase. Nine normal male subjects participated in 27 independent studies following pretreatment with 100 mg of carbidopa given every 8 hours for 2 days. Doses of 0.2, 0.4, and 0.8 mg/kg/hr of 5-hydroxytryptophan were initially infused for 30 minutes, and serum prolactin was measured every 15 minutes for 2 1/2 hours. The urinary 5-hydroxyindoleacetic acid/creatinine ratio was determined in aliquots collected during 3 hours before, during, and after the intravenous infusion. 5-Hydroxytryptophan at a dosage of 0.4 mg/kg/hr was the minimal amount to elicit a consistent and significant prolactin increase (p less than 0.01). A positive correlation (r = 0.907, p less than 0.002) was also demonstrated between the maximal prolactin response and the 5-hydroxyindoleacetic acid/creatinine ratio. Thus 0.4 mg/kg/hr of 5-hydroxytryptophan was administered sequentially three times at intervals of 2, 4, 6, 8, and 12 hours. With exception of the 12-hour interval a significantly smaller plasma prolactin increase was seen following the third dose of 5-hydroxytryptophan (p less than 0.05). Furthermore, the nadir for this diminished prolactin response occurred at 4 hours (p less than 0.01). This phenomenon may represent a down regulation of the serotonin receptors induced by the repetitive administration of 5-hydroxytryptophan. In conclusion, this study has demonstrated a dose-related prolactin response to increasing doses of 5-hydroxytryptophan. The maximum down regulation of prolactin release occurred when 5-hydroxytryptophan was administered at 4-hour intervals.

Variability and selectivity of anterior pituitary response to dopamine agonists throughout the normal menstrual cycle.

To clarify whether there is a variation of dopamine effect throughout the normal menstrual cycle, 24 studies were performed during the follicular, periovulatory, and luteal phase in seven ovulatory women. The subjects were studied for 24 hours after receiving two different dopamine agonists, 2.5 mg of bromocriptine in one cycle and 50 micrograms of pergolide in a subsequent cycle. Baseline plasma luteinizing hormone, follicle-stimulating hormone, prolactin, and thyrotropin were followed through time, and the dynamic responses to gonadotropin-releasing hormone and thyrotropin-releasing hormone before and at 6 and 22 hours after medication were studied. Since the results obtained with both agonists were similar, the data have been combined in a single group. Baseline luteinizing hormone levels (but not follicle-stimulating hormone) were significantly suppressed (p less than 0.01) during the follicular phase only, and the plasma luteinizing hormone and follicle-stimulating hormone response to gonadotropin-releasing hormone was not affected by the agonists in any of the three cycle phases. Baseline plasma prolactin was suppressed equally (p less than 0.005) in all phases of the cycle, and the response to thyrotropin-releasing hormone was similarly suppressed in all phases only at 6 hours (p less than 0.002). Baseline thyrotropin also was suppressed (p less than 0.01) in all phases but the degree of inhibition was greater in the luteal than in the follicular phase (p less than 0.05). The response to thyrotropin-releasing hormone was inhibited, with the smallest response seen at 22 hours (p less than 0.01). In conclusion, these results suggest that the modulatory effect of dopamine on pituitary hormone secretion is variable and selective throughout the normal menstrual cycle. The greatest inhibition is on prolactin release, which is similar in all phases, followed by thyrotropin, which is greater in the luteal phase, and then by luteinizing hormone in the follicular phase only; it has no effect on follicle-stimulating hormone release.

Pergolide and bromocriptine for the treatment of patients with hyperprolactinemia.

A prospective study of 22 women with hyperprolactinemia from various causes was performed with use of bromocriptine in nine patients and pergolide in 13 patients. The administration of 50 micrograms of pergolide followed by 100 micrograms on the second day showed significant decrements (p less than 0.01) in systolic and diastolic blood pressure in either standing or lying position. However, 25 micrograms of pergolide followed by 50 micrograms did not lower blood pressure. Both 25 and 50 micrograms of pergolide induced a maximal and significant (p less than 0.005) inhibition of prolactin at 8 hours and remained suppressed for at least 24 hours. Long-term treatment with either bromocriptine or pergolide was continued for 48 weeks. Both dopamine agonists demonstrated a similar degree of prolactin inhibition throughout time. However, only patients treated with pergolide had higher levels (p less than 0.05) of luteinizing hormone and follicle-stimulating hormone. Resumption of spontaneous menses and cessation of galactorrhea occurred at similar times in both groups. It can be concluded that either dopamine agonist can be safely given to patients with hyperprolactinemia.