Study on the hypothalamic dopaminergic activity in different stages of pregnancy and non-pregnancy

The purpose of this study was to investigate hypothalamic dopaminergic activity in pregnant women after the administration of metoclopramide (MCP), a dopamine receptor blocker, and to investigate the effects of MCP on the placental steroid and peptide hormones, and to clarify the prolactin (PRL) releasing mechanism in the hypothalamo-pituitary axis during pregnancy using dopaminergic agents and TRH. The following results were obtained. The plasma PRL levels following intravenous MCP remained significantly elevated for 180 minutes (p less than 0.001-0.05) in all groups as compared to the control group, but there were no significant differences between early and late pregnant groups, and between pregnant and nonpregnant groups. Therefore, the dopaminergic activity of the hypothalamus remained unchanged during pregnancy as well as in the nonpregnant state. The administration of MCP or a sudden increase in plasma PRL had no effect on the maternal plasma estradiol-17 beta, progesterone, HCG or HPL during pregnancy. PRL release from the pituitary by MCP was suppressed significantly (p less than 0.01) by pretreatment with bromocriptine. PRL releasing activity of MCP 10mg was significantly higher (p less than 0.01-0.05) than that of TRH 500 micrograms in the pregnant women.     

The incidence of transient hyperprolactinemia in gonadotropin-stimulated cycles for in vitro fertilization and its effect on pregnancy outcome

The incidence of transient hyperprolactinemia and its impact on in vitro fertilization (IVF) were determined in 151 euprolactinemic women with tubal infertility undergoing an identical gonadotropin stimulation for IVF. Prolactin (PRL) levels were measured on the morning of cycle day 3, days of human chorionic gonadotropin (hCG) administration, and peak estradiol (E2), and in the midluteal phase. Women were divided into high (H: peak E2 greater than 1,000 pg/mL, n = 51), intermediate (I:peak E2: 500 to 800 pg/mL, n = 50), or low (L:peak E2 less than 400 pg/mL, n = 50) E2 response groups. There was no difference in the incidence of hyperprolactinemia on cycle day 3 between the response groups (H:16%, I: 12%, and L:8%). However, high responders had a higher incidence of hyperprolactinemia than intermediate or low responders on all other study days. The incidence of hyperprolactinemia was greater than baseline (cycle day 3) only in the high responders on the day of peak E2. Serum prolactin was strongly correlated with peak E2 (r = 0.41). There were no differences in the number of preovulatory oocytes retrieved or fertilized or the pregnancy rates between hyperprolactinemic and euprolactinemic patients in each response group or when all hyperprolactinemic and euprolactinemic patients, regardless of E2 response, were compared. Transient hyperprolactinemia during gonadotropin stimulation for IVF occurs and correlates with E2 response but has no impact on IVF outcome.     

Pregnancy-induced changes in prolactinomas as assessed with computed tomography

Seven women with prolactin-secreting pituitary microadenomas and three with persistent hyperprolactinemia after surgical adenomectomies were evaluated with computed tomography to assess the effect of pregnancy on the volume of pituitary prolactinomas and hyperfunctioning pituitary tissue. In one patient a microadenoma enlarged to become a macroadenoma. Tumor enlargement occurred in the remaining six patients with microadenomas. None of the patients with previously resected adenomas exhibited hypertrophy of residual pituitary tissue or tumor recurrence after pregnancy.     

Bromocriptine inhibition of anesthesia-induced hyperprolactinemia: effect on serum and follicular fluid hormones, oocyte fertilization, and embryo cleavage rates during in vitro fertilization

Thirty-two patients undergoing in vitro fertilization (IVF) were given bromocriptine either 1 or 12 hours before anesthesia or received no drug to determine what effect suppression of transient, anesthesia-induced hyperprolactinemia would have on peripheral and follicular fluid hormones, fertilization and cleavage rates, and pregnancy. Thirty minutes after anesthesia, there was a 120-ng/mL rise in serum prolactin (PRL) in control patients versus an insignificant change in women given bromocriptine. Levels of PRL in follicular fluid were significantly less, and estradiol (E2) levels were higher (P less than 0.05) in all bromocriptine-treated patients compared with controls, whereas follicular fluid levels of progesterone (P), inhibin activity, and midluteal serum P were unaffected. Although fertilization and pregnancy rates were similar, a greater proportion of fertilized oocytes from bromocriptine-treated patients advanced to cleaving embryos compared with controls (95% versus 63%, respectively; P less than 0.001). We conclude that bromocriptine, given before anesthesia, can suppress transient, anesthesia-induced hyperprolactinemia and dramatically alter follicular fluid concentrations of PRL and E2. Although these changes in hormonal milieu affected neither oocyte fertilization nor pregnancy rate in our IVF patients, they seemed to have a positive influence on embryonic development after IVF.     

Stable prolactin level after enhanced estradiol production following dehydroepiandrosterone sulfate

To evaluate whether intravenous injection of dehydroepiandrosterone sulfate (DHEAS), by enhancing estradiol (E2) production, would stimulate prolactin (PRL) secretion in late pregnancy, maternal serum PRL was determined before and 1 to 5 hours after administration of 100 mg of DHEAS in a total of 41 women with normal or complicated late pregnancies (twin pregnancy, pre-eclampsia, intrahepatic cholestasis of pregnancy, diabetes). The basal serum PRL concentration in patients with diabetes was significantly lower than normal. The mean PRL level did not change significantly in any group in spite of the increase in serum E2 levels after the DHEAS injection. The lack of PRL response to a rapid rise in E2 may be due to the maximal inhibition of the PRL-inhibiting factor in the hypothalamus and/or maximal activation of the pituitary lactotrophs occasioned by the high estrogen environment during late pregnancy.     

Effects of pregnancy, delivery and lactation in hyperprolactinemia with prolactin producing pituitary adenoma

The effects of pregnancy, delivery and lactation on changes in serum prolactin (PRL) values were investigated in patients with hyperprolactinemia. Thirty-seven patients with hyperprolactinemia who wished to become pregnant were treated by transsphenoidal surgery, bromocriptine therapy, or a combination of the two. In 33 patients whose pre-pregnancy serum PRL concentration exceeded 30ng/ml, only in two did serum PRL return to the normal range below 30ng/ml after pregnancy, delivery and lactation. However, the serum PRL concentration was decreased in 28 patients. When classified according to the pre-pregnancy serum PRL concentrations, PRL less than or equal to 100 (Group A), 100 less than PRL less than or equal to 200 (Group B) and 200 less than PRL (Group C), patients with the greatest pre-pregnancy serum PRL concentration showed the greatest reduction. The ratios of post-pregnancy serum PRL to pre-pregnancy PRL in group A, B and C were 91.4 +/- 22.1%, 81.5 +/- 7.0% and 65.0 +/- 6.5% (Mean +/- SE), respectively. Group C with the highest pre-pregnancy serum PRL concentration consisted almost entirely of patients with macroadenoma. Thus, the reduction in serum PRL after pregnancy, delivery and lactation was considered to be the result of a decrease in the size of the adenoma due to adenoma enlargement over the sella turcica through the estrogen effects during pregnancy, and from impairment of pituitary circulation.     

Does transient hyperprolactinemia during ovarian hyperstimulation interfere with conception or pregnancy outcome?

The significance of transiently increased serum prolactin (PRL) levels on pregnancy rates in in vitro fertilization (IVF) is unknown. The aim of this study was to evaluate PRL levels in IVF patients who conceived and in matched controls who did not. Thirty-seven IVF cycles resulting in pregnancy and 74 nonpregnant cycles were compared. Prolactin was measured before ovarian stimulation with clomiphene citrate, and human menopausal gonadotropin and estradiol (E2) and PRL were measured 8 hours after human chorionic gonadotropin (hCG) administration at midcycle. Before ovarian stimulation, serum PRL levels were not different in the pregnant and nonpregnant women (11.1 +/- 0.6 [mean +/- standard error] micrograms/l and 10.1 +/- 0.4 micrograms/l, respectively). After hCG, PRL levels were significantly higher in the pregnant women than in the nonpregnant women (20.8 +/- 1.6 and 16.0 +/- 0.9 micrograms/l, respectively; P less than 0.005) and more pregnant than nonpregnant women had elevated PRL levels (49% versus 28%, respectively; P less than 0.05). There was no correlation between PRL and E2 in either group. The abortion rate was not different between the women with elevated PRL (22.2%) and the normoprolactinemic women (31.6%). These results do not support treatment of transient hyperprolactinemia with dopamine agonists in IVF patients.     

Prolactin response to thyrotropin-releasing hormone (TRH) in patients with hypothalamic-pituitary disease

The prolactin (PRL) response to thyrotropin-releasing hormone (TRH) was evaluated in 686 patients over a 4-year period. Of the 170 control subjects tested, none had a blunted PRL response to TRH. Eighty patients with prolactinomas documented by surgery were tested. Ninety-five percent (76 of 80) of these patients had an abnormally blunted PRL response to TRH. Of the 87 patients with a prolactinoma who did not undergo surgery, 98% (85 of 87) had a blunted PRL response to TRH. Many patients with other pituitary and hypothalamic diseases (pituitary tumors other than prolactinomas [Cushing's disease, acromegaly, chromophobe adenoma], craniopharyngioma) also had an abnormal PRL response to TRH (79 of 153, 52%). In the majority of patients with hyperprolactinemia due to dopamine antagonist medications, TRH stimulation did not produce a normal rise in PRL. The TRH test may be helpful in confirming the diagnosis of prolactinoma, but it is not a decisive factor in the diagnosis or management of this entity.     

Dysfunction of dopaminergic regulation of prolactin in patients with functioning and nonfunctioning pituitary adenomas and craniopharyngiomas

The response to domperidone (a dopamine blocking agent) of serum prolactin (PRL) levels was compared in 3 patients with amenorrhea-galactorrhea without evidence of a pituitary tumor, 23 patients with prolactinomas (10 cases with histologic confirmation), 7 patients with histologically verified large nonfunctioning pituitary adenomas with normal or moderately elevated basal PRL levels, and 6 patients with histologically verified craniopharyngiomas (3 with normal basal PRL levels and 3 with elevated PRL levels). The response was compared with that of 10 patients with postpartum hyperprolactinemia and 14 normal women. Ten milligrams of intravenous domperidone induced a rapid rise in PRL that was maximal at 30 to 45 minutes in normal, postpartum, and amenorrhea-galactorrhea patients who had no sign of tumor. In contrast, domperidone failed to induce significant changes in PRL in cases of prolactinoma, nonfunctioning pituitary adenomas, and craniopharyngioma with or without elevated basal PRL levels. The results suggest that dopaminergic control on PRL secretion was impaired in all tumor cases. The mechanisms of this abnormal dopaminergic control, however, may be different. Whereas dopamine control in cases of prolactinoma is altered at the level of pituitary dopamine receptors, alternative explanations must be found for those tumors with normal basal PRL levels and lack of response to domperidone.     

Hormonal and biochemical parameters in polyhydramnios

Fifteen consecutive cases of polyhydramnios (PH) out of a total number of 8806 deliveries performed between the 28th and the 41st week of pregnancy were investigated during the period from 1979 to 1985. Three cases of acute PH and 12 cases of chronic PH of which 10 were idiopathic were distinguished. From the time the clinical diagnosis was established until delivery, maternal serum and amniotic fluid α-fetoprotein (AFP) and prolactin (PRL), as well as maternal serum oestrogens (O_T), placental lactogen (HPL), chorionic gonadotropin (hCG) and pregnancy-specific β₁-glycoprotein (SP₁), were studied. A very high increase of maternal serum AFP in all the cases of PH was observed (p < 0.001) and was associated with the high degree of risk for obstetrical complications, while, on the other hand, amniotic fluid AFP was increased only in PH associated with congenital abnormalities of the fetus. Maternal serum PRL was not different from normal values (p > 0.2), while amniotic fluid PRL was lower in all the cases of chronic idiopathic polyhydramnios studied. The protein hormones and the oestrogens showed a discrepancy in their elevation, according to the kind of PH, the outcome of pregnancy, and the condition of the infant at birth.     

Clinical history and outcome of 59 patients with idiopathic hyperprolactinemia.

OBJECTIVE: To investigate the clinical course of hyperprolactinemia without demonstrable cause. DESIGN: Prospective study of all patients with idiopathic hyperprolactinemia first seen between 1974 and 1985. SETTING: Outpatient Department of University Hospital. PATIENTS: Fifty-nine patients followed for 6 to 190 months (median 78 months). Medical treatment given only in case of anovulatory infertility or hypogonadism. OUTCOME MEASURES: Development of pituitary (micro)prolactinoma, prolactin (PRL) levels, and clinical signs of menstrual dysfunction. RESULTS: With exception of one woman in whom it probably had been missed by hypocycloidal tomography, no demonstrable prolactinoma developed. Prolactin levels rose in two patients, one using oral contraceptives and the other with prolactinoma. At the end of follow-up, 15 of 16 patients using a dopaminergic drug had a normal cycle; 13 had normal final PRL levels. From the 43 patients off medication, 28 (66%) had normal PRL levels and 23 (54%) had a normal cycle. There were no significant differences between women who had and had not been pregnant. Dopaminergic medication had no appreciable influence on the course of the disease. CONCLUSION: In idiopathic hyperprolactinemia, progression to pituitary prolactinoma seldom, if ever, occurs. There is a high tendency to spontaneous cure, and pregnancy or medication have no apparent effect. Frequent pituitary imaging was found to be not necessary in our patient population. It may best be reserved for situations in which the PRL level in symptomatic hyperprolactinemia is inconsistent with pituitary imaging results.     

Hyperprolactinemia: pathophysiology and therapeutic approach

Abstract

Prolactin (PRL) is a hormone, mainly secreted by lactotroph cells of the anterior pituitary gland. Recent studies have shown it may also be produced by many extrapituitary cells. Its well-recognized PRL plays an important role in lactation during pregnancy, but it is involved in other biological functions such as angiogenesis, immunoregulation and osmoregulation. Hyperprolactinemia is a typical condition producing reproductive dysfunction in both sexes, resulting in hypogonadism, infertility and galactorrhea. It may be also asymptomatic. Lactotroph adenomas (prolactinoma) is one of the most common cause of PRL excess, representing approximately 40% of all pituitary tumors. Several other conditions should be excluded before a clear diagnosis of hyperprolactinemia is made. Hyperprolactinemia may be secondary to pharmacological or pathological interruption of hypothalamic–pituitary dopaminergic pathways or idiopathic. Stress, renal failure or hypothyroidism are other frequent conditions to exclude in patients with hyperprolactinemia. We will review biochemical characteristics and physiological functions of that hormone. Clinical and pharmacological approach to hyperprolactinemia will also be discussed.     

Retrograde time-scale analysis of human placental lactogen, beta human chorionic gonadotropin, and unconjugated estriol levels in human maternal serum from the onset of spontaneous labor

We analyzed on a retrograde time scale which calculated in maternal serum, from the onset of spontaneous labor, human placental lactogen (hPL), beta human chorionic gonadotropin (beta-hCG), unconjugated estriol (E3) levels, and the ratios among these hormones in the normal late pregnancy. Maternal serum hPL, beta-hCG, and unconjugated E3 levels were measured simultaneously and serially in regular menstrual sera from 27 women in late pregnancy (total 155 samples) by radioimmunoassay. The peak level of hPL was found at 2 weeks before labor, and the peak of beta-hCG was found during 2-4 weeks before the onset of spontaneous labor. On the other hand, the mean level of E3 rose slightly with advancing gestational age. The hormonal ratios of hPL to E3 and beta-hCG to E3 decreased gradually toward the onset of labor, but the ratios of hPL to beta-hCG did not change. From these data, it is possible to conclude that the onset of spontaneous labor can be predicted by measuring the levels of hPL and unconjugated E3 in maternal peripheral serum.     

米非司酮对早孕妇女血浆生殖激素及蜕膜和绒毛组织中前列腺素水平的影响

本文用放免法测定了妊娠35～67d妇女口服米非司酮100mg前和48h后血浆中E2、P、PRL、βhCG水平和妊娠40～56d口服米非司酮48h后蜕膜和绒毛组织中的PG（2α）、PGE2、TXB2和6－keto－PGF（1α）水平的变化。结果显示米非司酮使血浆P水平降低（P＜0．01）；PRL水平增加（P＜0．01）；E。在用药后48h继续呈上升趋势，但与用药前无显著统计学差异；E2／P和PRL／P比值增力。（P＜0．05，P＜0．01）。6－keto－PGF（1α）在用药后有腹痛和／或子宫出血受试者蜕膜组织中的水平明显高于无症状受试者和对照组；绒毛组织中PGF（2α）、TXB2和6－keto－PGF（1α）水平在用药后有腹痛和／或子宫出血者和无症状受试者都明显高于对照组（P＜0．05，P＜0．005），PGF（2α）／PGE2比值也明显增加（P＜0．05）。结果显示了来非司酮对早孕妇女的综合影响，包括改变内分泌激素之间和PGS之间比率的平衡，改变内分泌激素和PGs的浓度，促使子宫收缩及宫颈软化等。     

Hormone patterns during bromocriptine-induced pregnancy in hyperprolactinemic patients

Plasma prolactin (PRL) and human placental lactogen (HPL), and urinary estriol and pregnanediol were studied during pregnancies induced with bromocriptine (Parlodel, Sandoz) in 10 cases of hyperprolactinemia. Previous selective adenomectomy or intrasellar implantation of radioactive gold (¹⁹⁸Au) failed to induce a complete remission in 3 of these subjects.PRL rapidly increases after bromocriptine withdrawal, reaching values higher than those in normal women in the same stage of pregnancy within a few weeks. At term, pathological PRL levels occurred in 3 subjects only (with distinct alterations of the sella turcica).Estriol, pregnanediol and HPL were normal in all cases. These findings suggest that PRL levels higher than those normally observed during pregnancy do not alter fetoplacental endocrine function.     

Treatment of functional amenorrhea-galactorrhea with 2-bromoergocryptine.

The present study was undertaken to investigate not only the effectiveness of bromoergocryptine therapy in 13 women with amenorrhea-galactorrhea and hyperprolactinemia without evidence of organic pathology, but also to assess the value of pretreatment evaluation in predicting the response to therapy. Sella turcica tomography, base line serum follicle-stimulating hormone, luteinizing hormone (LH), thyroid-stimulating hormone, T4, plasma cortisol levels, and the growth hormone reserve were normal in all patients. The pretreatment administration of LH-releasing factor (LRF) (100 microng subcutaneously) resulted in either a normal or excessive release of LH. On bromoergocryptine therapy, cyclic menses were reintiated in 10 of the women, while conception occurred prior to reinitiation of menses in the remaining three women. The time required for resumption of menses or conception on therapy correlated well with the magnitude of gonadotropin response to LRF. No correlation was seen with pretreatment prolactin levels nor with the degree of suppression of prolactin during bromoergocryptine therapy. In four women the mean prolactin levels during therapy were above normal, and in one patient prolactin levels approached pretreatment values during therapy. The initiation of cyclic menses despite continued hyperprolactinemia may indicate a possible direct effect of bromoergocryptine on hypothalamic LRF secretion as a partial explanation for its therapeutic action. On discontinuation of bromoergocryptine therapy, serum prolactin levels rapidly returned to pretreatment values or higher in all of the patients studied. In contrast to previous studies in which amenorrhea recurred in all patients after discontinuation of therapy, three of our patients maintained cyclic menses despite continued hyperprolactinemia. The recurrence of hyperprolactinemia after discontinuation of bromoergocryptine would indicate a persistent autonomy of the mechanisms involved. Periodic endocrine evaluation will be necessary to substantiate the presence or absence of pituitary microadenoma in these women.     

Hormonal Causes of Male Sexual Dysfunctions and Their Management (Hyperprolactinemia,Thyroid Disorders,GH Disorders,and DHEA)

IntroductionBesides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD).AimTo review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD.MethodsA systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence‐Based Medicine—Levels of Evidence (March 2009) was applied when possible.Main Outcome MeasuresThe most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed.ResultsOnly severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL‐induced suppression on gonadotropin secretion. The latter is PRL‐level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin‐like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function.ConclusionsWhile the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in regulating male sexual functioning. Maggi M, Buvat J, Corona G, Guay A, and Torres LO. Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA). J Sex Med 2013;10:661–677.     

Luteal phase hyperprolactinemia during ovulation induction with human menopausal gonadotropins: incidence, recurrence, and effect on pregnancy rates

Hyperprolactinemia may develop during ovulation induction with human menopausal gonadotropins and hCG (hMG/hCG). Because elevated serum prolactin (PRL) has several adverse effects on female reproductive function, this event has been implicated as a factor to explain the difference between ovulation and pregnancy rates in hMG/hCG treatment cycles. The incidence and severity of hyperprolactinemia in the luteal phase of hMG/hCG-stimulated cycles was investigated in a large series of patients. We analyzed 240 consecutive, ovulatory hMG/hCG cycles in 96 women from July 1984 to January 1986. All women had failed to conceive with clomiphene citrate, and had normal luteal phase PRL levels during unstimulated cycles. Daily serum total estrogens were determined during hMG administration. Serum progesterone and PRL were determined in the mid-luteal phase (7 days post-hCG administration). In 7.5% of the cycles, luteal phase PRL elevations were greater than 25 ng/mL. Only 2.5% of cycles had levels of PRL greater than 35 ng/mL. Hyperprolactinemia infrequently recurred in different cycles of the same patient (two of 16 patients, 12.5%). Cycles with hyperprolactinemia were found to have significantly higher preovulatory estrogen levels. Serum progesterone levels were not significantly decreased in cycles with elevated PRL. Pregnancy rates in cycles with and without hyperprolactinemia were similar (7.7 versus 11.1%, respectively; P greater than .05). We conclude that the development of luteal phase hyperprolactinemia during ovulation induction with hMG/hCG is an isolated event. High preovulatory estrogen levels may predispose to its development. Because hyperprolactinemia is uncommon and is usually mild, other factors must be responsible for the difference between ovulation and pregnancy rates using hMG/hCG.     

Prolactin size variants during pregnancy in women with ovulatory hyperprolactinemia: characterization by isoelectric focusing and lectin affinity chromatography.

Previous studies from this laboratory have demonstrated the occurrence of important changes in PRL size heterogeneity in women with ovulatory hyperprolactinemia during gestation. A similar observation has been made, in normal women, for glycosylated PRL, which shows a progressive decrease as pregnancy progresses. In this study we decided to investigate the contribution of G-PRL on PRL heterogeneity throughout gestation in women with ovulatory hyperprolactinemia. Serum samples obtained throughout gestation were analysed by SDS-PAGE followed by immunoblotting and by isoelectric focusing of gels as well. The results indicated that, independent of the stage of pregnancy, the relative amounts of G-PRL as compared with the nonglycosylated form of the hormone remained quite constant. In addition, isoelectric focusing analyses of serum samples consistently resulted in an identical isoelectric point of PRL throughout all of the gestational period. These results suggested that changes in the relative proportions of PRL size species during pregnancy were not correlated with the degree of PRL glycosylation. Moreover, these observations further extended and supported the concept that the occurrence of PRL size heterogeneity depends mainly on thiol-disulfide interchange mechanisms, among PRL molecules, at the pituitary level.     

Effect of transitory hyperprolactinemia on in vitro fertilization of human oocytes

OBJECTIVE: To examine the changes in plasma prolactin (PRL) during ovarian hyperstimulation (OH) and the influence of hyperprolactinemia on folliculogenesis, oocyte retrieval and in vitro fertilization (IVF) success rates and the usefulness of the metoclopramide (MCP) test in predicting the onset of hyperprolactinemia. STUDY DESIGN: Forty-nine cycles of OH were induced in 32 infertile women using follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (GI) (n = 36), also in association with gonadotropin-releasing hormone (GII) (n = 13). The MCP test (10 mg, intravenously) was performed on fertile control women (control group, n = 9) and in GI (n = 21) and GII (n = 8) patients. RESULTS: Plasma PRL and estradiol levels increased during OH, reaching maximum levels on the day preceding oocyte retrieval in GI and GII. Since these two groups exhibited similar PRL curves, they were evaluated as a single group. Patients showing an increase in PRL of > 200% presented a greater number of follicles with a mean diameter > or = 12 mm and more mature oocytes and better IVF success rates than patients with a PRL increase < or = 200%. Oocyte retrieval did not differ between the groups. The MCP test showed hyperresponsiveness in the three groups studied, but no correlation was found between the PRL increase in this test and that during OH. CONCLUSION: Plasma PRL and estradiol levels increase during OH, while the MCP test cannot predict the onset of hyperprolactinemia. Transitory hyperprolactinemia seems to be associated with an increase in the numbers of follicles with a mean diameter > or = 12 mm and with more mature oocytes and better IVF success rates.