Sulpiride treatment during early human pregnancy: effect on the levels of prolactin, six steroids, and placental lactogen.

To study the role of PRL in the regulation of the production of 17 beta-estradiol, progesterone, testosterone, and human placental lactogen (hPL), 11 healthy women were given 150 mg sulpiride daily for 14 days, beginning between weeks 6--9 of normal gestation. Plasma PRL, estradiol, progesterone, testosterone, and hPL were measured before and 1 and 2 weeks after the start of sulpiride treatment, and the results were compared with those from 16 control women who were followed similarly but without sulpiride treatment. Sulpiride treatment induced significant (P less than 0.001) elevations of plasma PRL at 1 week [84.1 +/- 4.9 vs. 23.7 +/- 2.8 ng/ml (mean +/- SE)] and 2 weeks (83.0 +/- 4.1 vs. 31.9 +/- 4.1 ng/ml). No differences were observed in the concentrations of estradiol, progesterone, testosterone, or hPL. Two women treated with sulpiride reported mild uterine contractions, but no spontaneous abortion occurred in either group. It is evident that hyperprolactinemia or sulpiride treatment do not change the circulating concentrations of sex steroids and hPL between 6--11 of normal gestation.

Does bromocriptine block thyrotropin-releasing hormone-induced prolactin release during pregnancy?

PRL responses to 200 microgram of iv TRH were measured in 16 healthy women with normal early pregnancy before and at the endo of bromocriptine treatment of 5.0--7.5 mg daily for 1--2 weeks. Before the start of bromocriptine, TRH caused a PRL elevation from 19.1 +/- 2.2 to 95.2 +/- 12.6 ng/ml (mean +/- SE) after 20 min, with a mean maximal PRL increment of 71.7 +/- 11.6 ng/ml. Bromocriptine suppressed basal plasma PRL level to 3.6 +/- 0.8 ng/ml (P less than 0.001). TRH then caused a PRL rise to 18.8 +/- 1.8 ng/ml at 20 min, with a mean maximal PRL increment of 15.7 +/- 1.8 ng/ml. The absolute PRL response was significantly smaller (P less than 0.001) during bromocriptine intake than before, whereas the mean percent increments in PRL levels after TRH administration were similar in the presence and absence of bromocriptine. Fifteen of these women were restudied with TRH stimulation 4--6 weeks after legal abortion, and the PRL responses to TRH were normal. When 7 of these women were once again treated with bromocriptine and retested with TRH, no absolute or relative PRL response to TRH emerged. These results release differs between the pregnant and nonpregnant states.

Circadian and seasonal variation in human preovulatory follicular fluid melatonin concentration.

The concentrations of melatonin in 112 preovulatory follicular fluid (FF) samples obtained from 60 women undergoing in vitro fertilization and 27 patients at laparotomy during a spontaneous cycle were measured by RIA and compared with those in peripheral serum. The circadian and seasonal variations in FF melatonin were also analyzed. The FF melatonin concentrations in stimulated (mean +/- SEM, 61.9 +/- 6.4 pmol/L) and spontaneous cycles (98.1 +/- 8.9 pmol/L) were significantly higher (P less than 0.005) than those in peripheral serum (25.4 +/- 1.2 and 38.6 +/- 1.8 pmol/L, respectively), and in the stimulated cycles there was a positive correlation between them. The FF melatonin concentration in the morning (58.9 +/- 3.8 pmol/L) was significantly higher (P less than 0.005) than that in the daytime (23.2 +/- 0.8 pmol/L), but the morning concentrations did not differ between the light and the dark seasons of the year, whereas the daytime values were higher (P less than 0.005) during the dark season (27.1 +/- 2.1 pmol/L) than during the light season (21.1 +/- 2.1 pmol/L). The FF melatonin concentration did not correlate with follicular volume, and FF and serum melatonin concentrations showed no significant correlation with the serum concentrations of estradiol, progesterone, testosterone, or PRL. There were also no differences between FF melatonin concentrations in aspirates with or without an ovum. In summary, significant circadian and circannual variations in high FF melatonin concentrations were found, which suggest that melatonin could potentially interfere with the regulation of reproduction in humans at the follicular level.

Luteinizing hormone receptors in ovarian follicles of patients with polycystic ovarian disease.

Wedge resection was performed in 12 patients with polycystic ovarian disease, and cell samples from the cystic follicles were assayed for LH(hCG) receptor using [125I]iodo-hCG as a ligand hormone. Simultaneously to wedge resection, blood samples were taken for serum FSH, LH, 17 beta-estradiol, progesterone, and testosterone RIA measurements. Serum LH was regularly elevated (16.0-57.1 U/liter), whereas FSH (5.2-11.5 U/liter) was within the normal reference range. The LH to FSH ratio was between 2.1-7.8. The 17 beta-estradiol concentrations (0.12-0.23 nmol/liter) were within the normal reference range found during the early follicular phase. Only 3 patients had progesterone levels exceeding the assay sensitivity limit of 0.1 nmol/liter. Ony 3 of the 11 patients assayed for serum testosterone had values exceeding the upper limit of the reference range. Seventy-seven percent of the ovarian follicular samples showed specific binding of [125I]iodo-hCG. The number of receptors in positive samples averaged 0.67 +/- 0.11 fmol/mg homogenate protein, which is clearly lower than that in normal preovulatory follicles. Scatchard analyses revealed a single class of binding sites, with a mean equilibrium association constant of 5.4 X 10(9) M-1 at 37 C. These results suggest that the derangement of follicular development in patients with polycystic ovarian disease probably is not due to the lack of appearance of the LH(hCG) receptor. It is possible that the tonic elevation of serum LH results in a decrease in the number of available receptor sites; this would be one step in the process leading to ovarian changes characteristic of this disease.

Short and long term effects of growth hormone on circulating levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1, and insulin: a placebo-controlled study.

The short and long term effects of GH on serum concentrations of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin were investigated in women participating in an in vitro fertilization program. In this placebo-controlled study, sterile saline (eight women) or 24 IU GH (eight women) were given im on alternate days, starting on cycle day 4, in combination with GnRH and human menopausal gonadotropin. IGFBP-1 levels decreased significantly during the first 4 h after GH administration, whereas no significant changes were seen in the placebo group. The concentrations of serum IGF-I and insulin did not change during 4 h after GH injection. During the 11-day follow-up period, serum levels of both IGF-I and insulin were significantly higher in GH-treated than in placebo-treated women. These results suggest that the serum concentration of IGFBP-1 is not completely GH independent. They also support the earlier findings that long term treatment with GH increases serum IGF-I and insulin levels.

The ratios of serum bioactive/immunoreactive luteinizing hormone and follicle-stimulating hormone in various clinical conditions with increased and decreased gonadotropin secretion: reevaluation by a highly sensitive immunometric assay.

Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 +/- 0.21 to 3.71 +/- 0.36 (mean +/- SEM) at 120 min (P less than 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women (n = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 +/- 0.22 to 2.59 +/- 0.24, and the B/F ratio from 1.78 +/- 0.22 to 2.90 +/- 0.30 (P less than 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (less than 0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of +/- SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 +/- 0.5 to 0.14 +/- 0.03 (P less than 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 +/- 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 +/- 0.49, and the B/F ratio was 3.53 +/- 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P less than 0.01 for all).(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of steroid and steroid sulfate production and aromatase activity in cultured human granulosa-luteal cells.

The regulation of the production of steroids and steroid sulfates and the activity of aromatase in human luteinized granulosa cells were investigated. The cells were cultured for 48 h in the presence or absence of hCG and FSH. Basal production of pregnenolone (Pre, 0.3 +/- 0.03 ng/micrograms protein) and progesterone (P, 19.3 +/- 1.7 ng/micrograms protein) were high compared with that of other steroids beyond P in the steroidogenic pathway. The concentration of 17 alpha-hydroxyprogesterone (17-OHP) was lower 0.17 +/- 0.06 ng/micrograms and that of other steroids in the 4-ene and 5-ene pathways and steroid sulfates less than 0.05 ng/micrograms. Both hCG and FSH (100 ng/ml) stimulated the production of Pre and P 3- to 5-fold, but only minimal stimulation of other steroids and steroid sulfates was observed. Aromatase activity of granulosa-luteal cells was measured from the rate of formation of 3H2O from 1 beta-[3H]androstenedione (1 beta[3H]A) after exposing the cells to hCG, FSH or estradiol (E2) for 48 h. Basal aromatase activity was relatively low, but hCG and FSH stimulated aromatase 8- and 4-fold, respectively. The incubation of granulosa-luteal cells with E2 did not affect basal aromatase activity, but E2 augmented FSH-stimulated aromatase 1.4-fold (P less than 0.025). The results suggest that there is low 17 alpha-hydroxylase and steroid sulfokinase activity in human granulosa-luteal cells. Aromatase activity in these cells is regulated by both hCG and FSH, and intra-ovarian estrogens may regulate granulosa cell aromatase activity.

Naproxen sodium in dysmenorrhea secondary to endometriosis.

Twenty patients with moderate to very severe painful menstrual periods secondary to endometriosis were treated in a double-blind, four-period, crossover clinical trial with naproxen sodium and placebo. Complete or substantial pain relief was obtained in 83% of the cases of painful menstruation with naproxen sodium and in 41% with placebo (P = .008). Only 5% of the naproxen sodium-treated women needed supplemental analgesics compared with 36% of the placebo-treated women (P = .002). There was a trend towards diminished interference of dysmenorrhea with normal patient activities during naproxen sodium treatment compared with placebo (P = .069). No significant side effects occurred with either treatment. These results indicated that naproxen sodium is efficacious and safe for the treatment of menstrual distress in patients with endometriosis.

Experimental hyperprolactinemia and hypoprolactinemia and human chorionic gonadotropin during early pregnancy.

The effect of experimental hyperprolactinemia and hypoprolactinemia on human chorionic gonadotropin (hCG) concentration was studied in 34 healthy volunteers between weeks 6 and 11 of normal pregnancy. Hyperprolactinemia was induced in 12 women with 150 mg of sulpiride daily for 2 weeks; treatment led to a mean plasma prolactin (PRL) rise from 14.6 to 84.1 microgram/liter after 1 week and to 83.0 microgram/liter after 2 weeks. Hypoprolactinemia was effected in 11 women wit 5.0 to 7.5 mg of bromocriptine, daily for 2 weeks; treatment decreased the mean plasma prolactin from 19.2 to 6.0 microgram/liter after 1 week and to 5.2 microgram/liter after 2 weeks. These PRL changes were significant (P less than .001) in comparison with the plasma PRL concentrations in the 11 control women. Hyperprolactinemia induced by the sulpiride treatment was accompanied by a significant decrease in hCG concentration, whereas no difference in hCG was seen between hypoprolactinemia and control groups. This may suggest a synergistic action of hCG and PRL, or a direct effect of sulpiride on hCG, but the final mechanism and biologic importance of the phenomenon remain to be investigated.

Bromocriptine and norethisterone in the treatment of premenstrual syndrome.

Thirty-six women suffering from premenstrual syndrome were treated with bromocriptine or norethisterone in a randomized placebo-controlled double-blind study. Bromocriptine decreased breast engorgement and irritability (P less than .01) and also decreased the total score of all symptoms (P less than .05). Weight gain during the luteal phase was smaller (P less than .05) during bromocriptine than during placebo treatment. Norethisterone treatment alleviated (P less than .05) breast tenderness. Changes in hormonal parameters and liver function tests during bromocriptine treatment were minimal, whereas norethisterone decreased serum levels of luteinizing hormone (P less than .01), follicle-stimulating hormone (P less than .001), and progesterone (P less than .05), while increasing the serum level of prolactin (P less than .01) and gamma-glutamyltranspeptidase activity (P less than .05). Serum levels of cholic acid and chenodeoxycholic acid remained unchanged during both therapies. Bromocriptine treatment brought about side effects in 6 and norethisterone in 3 women. At the doses used, bromocriptine appears more efficient than norethisterone with regard to premenstrual symptoms, although norethisterone is better tolerated.

Measurement of the ovarian follicle by ultrasound in ovulation induction.

Ultrasonic monitoring of ovarian follicles and estimation of serum estradiol were carried out in 12 patients with clomiphene therapy, in 5 patients with gonadotropin therapy, and in 7 normal controls. The average diameter of preovulatory follicles in normal controls was 12,8 mm; in ovulation induction groups it was 2 to 4 mm greater. The level of serum estradiol was also higher in ovulation induction groups than in normal controls. The combined use of these two methods is recommended: ultrasonic monitoring to minimize the risk of multiple pregnancies and estrogen level monitoring to minimize the risk of hyperstimulation. Ultrasound is also safe and practical in following the size of hyperstimulated ovaries.

Luteinizing hormone receptor disorder in endometriosis.

Luteinizing hormone (LH) receptor concentrations in ovarian follicles and corpora lutea were measured in 51 patients with histologically proven endometriosis and in 41 control patients. The LH receptor concentrations in cases of endometriosis were lower during the early (0.43 +/- 0.11 [mean +/- standard error] versus 1.31 +/- 0.27 fmol/mg protein; P less than 0.001) and late (0.48 +/- 0.10 versus 1.59 +/- 0.22 fmol/mg protein; P less than 0.001) follicular phase, and during the late luteal phase (2.62 +/- 0.55 versus 4.62 +/- 0.65 fmol/mg protein; P less than 0.05) of the cycle than in control patients. In contrast to the control patients, the LH receptor concentration during the follicular phase remained constant in endometriosis, being lower in patients with extensive or severe disease than in patients with moderate or mild disease (0.28 +/- 0.07 versus 0.61 +/- 0.21 fmol/mg protein; P less than 0.05). Endometriosis-associated infertility might be a consequence of a defect in the mechanism mediating LH action in the ovaries.

Medroxyprogesterone acetate supplementation diminishes the hypoestrogenic side effects of gonadotropin-releasing hormone agonist without changing its efficacy in endometriosis.

OBJECTIVE: To examine the effects of concomitant use of goserelin and medroxyprogesterone acetate (MPA) in the treatment of endometriosis. DESIGN: Thirty-eight women with laparoscopically confirmed endometriosis were treated with once-a-month s.c. injections of goserelin acetate 3.6 mg (Zoladex depot; Zeneca Pharmaceutics, Cheshire, United Kingdom) randomly combined with either MPA (100 mg daily; n = 19) or a placebo (one tablet daily; n = 19) in a double-blind trial. Symptoms and side effects were monitored for a treatment period of 6 months and a follow-up period of 6 months. Blood and urine samples were collected for the assessment of endocrine and biochemical parameters. A second-look laparoscopy was performed 6 months after the treatment in 29 women. RESULTS: The extent of endometriosis was diminished similarly in both treatment groups, as were pelvic symptoms. Fewer women in the MPA group had hot flushes and sweating at 3 and 6 months of treatment. Sex hormone-binding globulin decreased in the MPA group but not in the placebo group. Consequently, the E2 index (E2/SHBG X 100), reflecting the free fraction of E2, fell more in the placebo group than it did in the MPA group. The increased urinary excretion of calcium observed during placebo treatment was prevented by MPA. CONCLUSION: High-dose MPA combined with a GnRH agonist (GnRH-A) diminished some antiestrogenic effects of the agonist. A reduction in hypoestrogenic side effects and a possible bone-sparing effect can be regarded as beneficial, especially as the good effect of the GnRH-a on endometriotic implants and pelvic symptoms prevailed.

Serum bile acid concentrations as an indicator of liver dysfunction induced during danazol therapy.

The effects of danazol therapy (600 mg/day) on the liver function of 16 women with endometriosis were investigated. The primary bile acids (cholic acid [CA] and chenodeoxycholic acid [CDCA]) were analyzed with radioimmunoassays in the fasting state and after a test meal. Also, the conventional liver function tests were performed. Ultrasonography was used to detect any possible changes in the gallbladder function. The fasting concentrations of CA increased (P less than 0.05) during therapy, while those of CDCA did not change. The ratio of CA/CDCA also increased (P less than 0.001). The maximal response of CA after the test meal increased (P less than 0.01) during the trial. As regards the other liver function tests, only the transaminases significantly increased (P less than 0.01) after 1 month of therapy but showed a tendency to decrease later during the trial. The gallbladder's volume and function did not change. All the parameters studied normalized within 1 month of cessation of danazol therapy. Danazol seems to have a rather mild effect on liver function. The analyzed parameters indicate transient cell wall injury and slight disturbances in liver cell uptake and secretion mechanism and also of synthesis activity.

Placebo-controlled study on serum concentrations of CA-125 before and after treatment of endometriosis with danazol or high-dose medroxyprogesterone acetate alone or after surgery.

Serum concentrations of CA-125 were determined in association with 6-month medical (n = 48) or surgical and medical therapy (n = 40) of endometriosis. The concentration of CA-125 was significantly higher in stages III + IV (66.6 +/- 22.0 [standard deviation] U/ml) than in stage I (20.9 +/- 2.3 U/ml) or II (28.4 +/- 2.8 U/ml); in stage II, the concentration was higher than in stage I. Surgical elimination of endometriosis significantly decreased the level of CA-125, as did danazol, but not medroxyprogesterone acetate (MPA), although these drugs were equal in clinical efficacy. The CA-125 changes during hormonal treatment did not correlate with the clinical response. Postoperatively, CA-125 responses to danazol, MPA, or placebo did not differ significantly from each other. During the 6-month follow-up after medication, the CA-125 concentrations tended to increase, especially in danazol-treated women. The determination of CA-125 is useful in estimating the extent of the disease, but it is less valuable in monitoring the treatment effect. The ability of danazol to suppress CA-125 expression emphasizes the specific properties of this drug.

Steroidal regulation of endometriosis tissue: lack of induction of 17 beta-hydroxysteroid dehydrogenase activity by progesterone, medroxyprogesterone acetate, or danazol.

Cytosol and nuclear estrogen receptors were detected in 73% and 89% of untreated endometriosis specimens, respectively. The corresponding figures for cytosol and nuclear progestin receptors were 94% and 100%, respectively. Compared with the endometrium, the concentrations in endometriosis tissue were low. The anatomic site, the severity of the disease, and the phase of the menstrual cycle had no significant influence on receptor concentrations in endometriosis tissue. The activities of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not increase during the luteal phase. Danazol for 1, 3, 7 to 11, and 18 to 30 days, or medroxyprogesterone acetate for 5 days, had no effect on receptor concentrations or 17 beta-HSD activity in endometriosis tissue. The frequent presence of the receptors suggests that endometriosis lesions are under the control of steroid hormones. The lack of effect by progesterone and progestins on 17 beta-HSD shows that this regulation is different in endometriosis tissue and in the endometrium.

Gonadotropin pulsatility in a stimulated cycle: clomiphene citrate increases pulse amplitudes of both luteinizing hormone and follicle-stimulating hormone.

OBJECTIVE: To elucidate gonadotropin secretory patterns during ovarian hyperstimulation for in vitro fertilization. DESIGN: All volunteers who attended the unit during a period of 3 months were prospectively investigated. SETTING: Infertility unit of the University Central Hospital of Oulu. PARTICIPANTS: Normally menstruating tubal infertility patients (n = 8) and healthy women with ovulatory cycles (hospital personnel, n = 11). All patients finished the study. INTERVENTIONS: Clomiphene citrate (CC), 50 mg, was administered on cycle days 5 to 9 and 300 IU of pure follicle-stimulating hormone (FSH) on cycle day 7 and 150 IU on cycle day 8. MAIN OUTCOME MEASURES: Serum samples for luteinizing hormone (LH) and FSH measurements were collected at 10-minute intervals for 6 hours on cycle day 7 (effect of CC) and day 9 (effect of CC/FSH), and the data were analyzed with the Munro computer program. RESULTS: The number of LH peaks was identical in the controls and study subjects on cycle days 7 and 9, whereas the pulse amplitude (P less than 0.025) and the pulse area (P less than 0.01) were higher in the CC/FSH-treated patients. The increase in overall mean LH level during the hormone therapy was not significant. In the CC/FSH-treated women, a decreased number of FSH pulses (P less than 0.01) with increased amplitude (P less than 0.001) and pulse area (P less than 0.01) was found. Clomiphene citrate treatment increased the mean FSH level (control versus cycle day 7, P less than 0.05) which was further increased (cycle day 7 versus cycle day 9, P less than 0.05) by FSH administration on cycle days 7 to 8. Otherwise pure FSH was found to be unable to modify endogenous LH or FSH secretory patterns under these conditions. CONCLUSIONS: Clomiphene citrate increases the amplitudes of both LH and FSH pulses in the midfollicular phase of a stimulated cycle, an effect which is not influenced by pure FSH administration.

Short-term effects of testolactone on human testicular steroid production and on the response to human chorionic gonadotropin.

Testicular responsiveness to a single dose of human chorionic gonadotropin was studied in five normal men before and during short-term treatment with an aromatization inhibitor, testolactone (TL). TL alone resulted in significant increases in the serum concentrations of progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, and the sulfate conjugates of pregnenolone, 17-hydroxypregnenolone and testosterone (T). Concentrations of 5-androstene-3 beta, 17 beta-diol and T remained unchanged, and those of estradiol (E2) decreased. TL had no major influence on serum luteinizing hormone, follicle-stimulating hormone, prolactin, or sex-hormone-binding globulin concentrations. During TL administration, human chorionic gonadotropin stimulation led to a significantly decreased E2 response, but the T response was unchanged. Alleviation of an inhibitory influence of E2 on the steroidogenic enzymes, especially 17,20-desmolase, was probably the reason behind the increased synthesis of several T precursors. In addition, TL appeared to have an inhibitory influence on the 17 beta-reduction of T precursors. TL resulted in increased serum concentrations of some steroid sulfates, but the mechanism of this effect remains unclear.

Anterior pituitary dysfunction during the luteal phase following ovarian hyperstimulation.

The capacity of the pituitary to secrete prolactin (PRL) and gonadotropins was investigated during the luteal phase of eight normally menstruating tubal infertility patients after ovarian stimulation with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin. The baseline values of PRL were significantly higher (P less than 0.025), those of luteinizing hormone unchanged, and those of follicle-stimulating hormone lower (P less than 0.025) during the treatment than in the control cycles. The maximal response of PRL to the dopamine antagonist metoclopramide was increased (P less than 0.01), whereas the maximal responses of luteinizing hormone (P less than 0.025) and follicle-stimulating hormone (P less than 0.001) to gonadotropin-releasing hormone were lowered in the treatment cycles. The current results indicate that ovarian hyperstimulation with clomiphene citrate/human menopausal gonadotropin/human chorionic gonadotropin may induce luteal phase pituitary dysfunction, which may affect the luteal phase functions of the corpus luteum.

Type IV collagenolytic activity in human preovulatory follicular fluid.

During normal ovulation, the two basement membrane layers of the ovarian follicle are degraded locally. The main component of basement membranes is type IV collagen, which is specifically cleaved by type IV collagenase. According to our results, type IV collagenolytic activity is present within follicular fluid and increases toward ovulation, decreasing rapidly as the follicles rupture. These results suggest that importance of type IV collagenolytic activity in the ovulatory process.