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Effects of combined clomiphene citrate and exogenous oestrogen or progesterone on the vaginal epithelium of ovariectomised rats.

The interactive effects of clomiphene citrate (CC) and exogenous oestrogen (E2) or progesterone (P4), on the vaginal epithelium of ovariectomised rats were examined using scanning electron microscopy and light microscopy. Results were compared with P4E2 treatment. Statistical analysis showed no significant difference between the two combination CC treatments. All treatment groups had the ability to stimulate a dormant epithelium and cause surface modifications in the form of individually elongated microvilli and rosette formations. The results of this study indicate that while P4 enhances the oestrogenicity of CC, there is no cumulative oestrogenic effect when E2 and CC are combined, but there is modification of cell surface organisation and evidence of anti-oestrogenic activity.

Animals↗

Effects of clomiphene citrate on serum hormone levels and endometrial thickness in an in vitro fertilization and embryo transfer program.

Hormonal alterations and pregnancy rates were compared between the clomiphene citrate (CC)-hMG combination cycle and the hMG cycle alone in an in vitro fertilization and embryo transfer program. In the CC-hMG cycle, the numbers of follicles developed, oocytes recovered and embryos transferred were higher than those in the hMG cycle (p less than 0.01, p less than 0.01 and p less than 0.05, respectively). Pregnancy rates of the CC-hMG cycle (6.7%/operation, 7.1%/embryo transfer), however, were lower than those of the hMG cycle (25%/operation, 31.6%/embryo transfer). PRL levels in the hMG cycle increased according to estradiol levels. In the CC-hMG cycle, CC might inhibit estradiol-induced hyperprolactinemia and the increase was lower even if the estradiol level was much higher than that of the hMG cycle until day 2. On day 4, the PRL level in the CC-hMG cycle further increased. The thickness of endometrium on day -2 in the hMG cycle alone was much thicker than that in the CC-hMG cycle (9.8 +/- 0.4 vs. 6.8 +/- 0.4 mm, mean +/- SEM).

Clomiphene↗

Effect of clomiphene citrate on hormonal profile in male hemodialysis and kidney transplant patients.

The aim of this study was to evaluate the role of clomiphene citrate (CC) therapy in the hypothalamus-pituitary-gonadal axis of male uremic subjects. Thirty-four patients on hemodialysis (HD) and 8 successful kidney transplant subjects (RT) were evaluated. Nine healthy males were used as controls (C). At baseline, zinc, testosterone (TEST), prolactin (PRL), FSH, LH and estradiol plasma concentrations were measured. All subjects were treated with CC (100 mg/day) for a week. The aforementioned parameters were determined again on the seventh day of CC therapy, and 3 days after drug withdrawal. Following CC, there was a rise in FSH, LH and TEST levels in all subjects (p < 0.05); it is interesting to stress that TEST became normal in HD. In addition, we observed a decrease of PRL after CC only in HD patients (p < 0.01). In summary, CC was able to partially correct most of the hormonal disturbances of the gonadal axis in uremic patients.

Adult↗

Exogenous estrogen therapy concurrent with clomiphene citrate--lack of effect on serum sex hormone levels and endometrial thickness.

The antiestrogenic action of clomiphene citrate (CC) is claimed to have an adverse effect on the development of the secretory endometrium. This effect can be assessed: (1) sonographically by measuring endometrial thickness, and (2) by serum hormone levels. The aim of this study was to evaluate whether administering ethinyl estradiol (EE) during CC treatment has any effect on endometrial thickness and/or hormone levels. Seventeen patients were treated with CC for one cycle and with CC plus EE in an adjacent cycle either before or after. The patients were followed by daily assessment of endometrial thickness, follicular growth and serum estradiol levels as well as midluteal prolactin and progesterone levels. We did not find any significant difference in either endometrial thickness, estradiol level, midluteal prolactin or progesterone levels between the two treatment protocols. We conclude that exogenous EE, in the dosage used in this study, does not overcome CC-induced alterations in endometrial thickness.

Anovulation↗

Comparison of the long-term effects of estrogen and clomiphene citrate on pituitary and uterine function in ovariectomized rats.

The effects of estradiol-17 beta (E2) and clomiphene citrate (CC) on pituitary-uterine function in ovariectomized (OVX) rats were compared in two experiments. In experiment 1, CC completely blocked E2 stimulation of uterine weight when administered concurrently for 10 and 30 days. In experiment 2, content of total (occupied and unoccupied) uterine nuclear estrogen receptors was increased by E2, but not by CC, compared to OVX controls. Only a fraction of the nuclear receptors was occupied in E2-treated rats, whereas all of these receptor sites were occupied in CC-treated rats. In addition, uterine cytoplasmic estrogen receptors were increased by E2 and diminished by CC treatment. Both E2 and CC were effective in preventing the postovariectomy rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), although LH was always inhibited to a greater extent than FSH. After 30 days of treatment, pituitary gonadotropins were also substantially reduced by E2 and CC, suggesting that long-term treatment decreased both pituitary synthesis and release. An increase in pituitary weight observed in E2-treated rats only was due largely to the stimulation of lactotropes, as serum prolactin was increased. In summary, although CC and E2 similarly depressed pituitary gonadotropin secretion, they exhibited marked differences in the stimulation and occupancy of uterine estrogen receptors and the stimulation of pituitary prolactin secretion.

Animals↗

Combined mesterolon-clomiphene citrate therapy for treatment of oligospermia.

42 subfertile patients with normal levels of plasma testerone (26 subnormal, suffering from oligospermia) have been treated with a combination of clomiphene citrate (50 mg Clomid daily) and mesterolon (50 mg Proviron daily) over a period of at least 3-6 months. The treatment resulted in pregnancy in 6 cases and in a significant improvement of the sperm count in 16. In 7, however, whilst the sperm count improved the qualitative results were unsatisfactory as many sperms were immature. Restricted spermatogenesis and a sperm count below 5 million/ml must be considered unfavourable but does not constitute a counter-indication to the combined therapy. No hazardous complications were observed.

Cell Count↗

Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation.

Letrozole was compared with clomiphene citrate (CC) as a first-line treatment for ovulation induction in women with polycystic ovaries (PCOs). A total of 106 women with primary infertility and a diagnosis of PCOs were randomized to receive either 100 mg CC (n = 55) or 2.5 mg letrozole (n = 51) daily for 5 days. Human chorionic gonadotrophin (hCG) at a dose of 10000 IU was administered when at least one follicle with a mean diameter > or = 18 mm was observed using transvaginal ultrasound. The number of mature follicles was significantly lower, but endometrial thickness and ovulation and pregnancy rates were significantly higher in the letrozole group than in the CC group. In conclusion, letrozole is associated with a higher pregnancy rate than CC in PCO patients and may have a role as a first-line treatment for anovulatory patients with PCOs.

Adult↗

Conception rates in clomiphene citrate cycles with and without hormone supplementation: a pilot study.

OBJECTIVE: A trial was conducted to examine the effects of a timed sequence of hormone supplementation (HS) with oral estradiol (E(2)) and vaginal progesterone (P) following clomiphene citrate (CC) therapy to determine if this regimen can increase pregnancy rates in CC cycles. METHODS: This study was a randomized, open-label study. Seventy-one oligo-ovulatory women were randomized into one of two groups; those who received CC plus HS (n = 34) and those who received no HS (n = 37). All subjects received 100 mg CC orally from cycle days 3 to 7. Subjects randomized to HS started oral E(2) at a dose of 1.5 mg BID on cycle day 8. All subjects monitored urine luteinizing hormone (LH) levels starting on cycle day 10; additionally, intercourse was encouraged starting on cycle day 10. Subjects receiving HS discontinued E(2) with LH surge and started using vaginal progesterone gel (Prochieve 8%) daily for 2 weeks starting 3 days after LH surge. All subjects had a pregnancy test (Assure) 2 weeks after LH surge. If pregnancy occurred, the subject continued using vaginal progesterone gel daily for an additional 10 weeks. RESULTS: Sixty-five (65) subjects (31 CC plus HS and 34 no HS) completed the study. Fifty of the 65 subjects (77%) (23 [74%] CC plus HS, 27 [79%] no HS) who completed the study ovulated. The mean (range) progesterone (P) concentration for these 50 subjects was 1662.6 (340 to 5690) ng/dL, and mean and median P levels were slightly higher, but not statistically significant, in the HS group compared with the no HS group. Pregnancy rates were clinically, but not statistically, different between the treatment groups. Of the 50 responders, 12% became pregnant (17% CC plus HS, 7% no HS). CONCLUSION: These findings show a potential supportive effect on pregnancy rates in the CC plus oral estradiol and vaginal progesterone gel group compared to CC alone that needs to be confirmed in a larger study.

Adult↗

Effects of the antiestrogens tamoxifen and clomiphene on bone resorption in vitro.

The in vitro effect of the nonsteroidal antiestrogens tamoxifen (TAM) and clomiphene (CLO) on bone resorption was investigated. TAM (100 microM) and CLO (100 microM) completely blocked PTH (2 nM)-induced resorption; 10 microM TAM was ineffective in blocking resorption, while 40-50 microM partially inhibited the response. TAM (100 microM) also completely blocked prostaglandin E2 (30 nM)- and 1,25-dihydroxy vitamin D3 (0.5 nM)-induced bone resorption. A 16-h pretreatment with TAM blocked subsequent stimulation of resorption by PTH, whereas 3.5- or 7-h pretreatment with antiestrogen was ineffective in blocking the response. Both protein and DNA syntheses were inhibited by continuous treatment (48 h) with the antiestrogens. When antiestrogen-pretreated (16 h) bones were transferred to fresh medium not containing antiestrogen, protein and DNA syntheses recovered to approximately half the control (nonantiestrogen-treated) values within 48 h. Bone resorption, however, was still completely inhibited even though macromolecular synthesis had substantially recovered. Thus, mechanisms other than macromolecular synthesis inhibition could be involved in the inhibition of bone resorption by the nonsteroidal antiestrogens TAM and CLO.

Animals↗

Clomiphene prevents cancellous bone loss from tibia of ovariectomized rats.

Estrogen inhibits postmenopausal bone loss and decreases fracture risk. Unfortunately, estrogen replacement therapy has many undesirable side effects, the majority of which are due to stimulation of reproductive tissues. Tissue specific estrogen agonists provide a promising new alternative to natural estrogens for hormone replacement. Clomiphene (CLO) is a substituted triphenylethylene antiestrogen based on its ability to antagonize estrogen-mediated uterine growth in rodents. CLO is used clinically for the treatment of disorders of ovulation in patients wishing to become pregnant. In order to determine whether CLO has tissue selective actions, we performed a dose-response study in adult (6-month-old) ovariectomized (OVX'd) rats. The rats received daily (gavage) doses of either 17 alpha-ethynyl estradiol (E) (0.1 mg/kg) or CLO (0.01-10 mg/kg) daily for 5 weeks. Long-term loss of ovarian function had no effect on serum cholesterol, greatly decreased uterine weight, cancellous bone area and trabecular number, and increased bone formation rate (BFR) and osteoblast and osteoclast perimeters. E treatment of OVX'd rats prevented uterine atrophy, greatly lowered cholesterol, and prevented many of the bone changes. CLO was a very weak estrogen agonist in supporting uterine weight, a partial agonist in reducing serum cholesterol, and an excellent agonist in maintaining normal bone mass and indices of bone turnover. We conclude from these studies that CLO exhibits pronounced tissue selective estrogen agonism in the rat. Specifically, CLO is effective in preventing cancellous bone loss in the OVX'd rats and has minimal uterotrophic activity.

Animals↗

Differential responses of estrogen target tissues in rats including bone to clomiphene, enclomiphene, and zuclomiphene.

The substituted triphenylethylene antiestrogen clomiphene (CLO) prevents cancellous bone loss in ovariectomized (OVX'd) rats. However, CLO is a mixture of two stereoisomers, enclomiphene (ENC) and zuclomiphene (ZUC), which have distinctly different activities on reproductive tissues and tumor cells. The purpose of the present dose response study was to determine the effects of ENC and ZUC on nonreproductive estrogen target tissues. These studies were performed in 7-month-old female rats with moderate cancellous osteopenia that was established by ovariectomizing rats 1 month before initiating treatment. OVX resulted in increases in body weight, serum cholesterol, endocortical resorption, and indices of cancellous bone turnover, as well as decreases in uterine weight, uterine epithelial cell height, bone mineral density, bone strength, and cancellous bone area. Estrogen treatment for 3 months restored body weight, uterine histology, dynamic bone measurements, and osteoblast and osteoclast surfaces in OVX'd rats to the levels found in the age-matched sham-operated rats. In contrast, estrogen only partially restored cancellous bone volume and uterine weight, and it reduced serum cholesterol to subnormal values. CLO was a weak estrogen agonist on uterine measurements and a much more potent agonist on body weight, serum cholesterol, and dynamic bone measurements. CLO increased trabecular thickness in osteopenic rats and was the most effective treatment in improving cancellous bone volume and architecture. ZUC was a potent estrogen agonist on all tissues investigated and had dose-dependent effects. In contrast, ENC had dose-dependent effects on most measurements similar to CLO and decreased the uterotrophic effects of ZUC. It is concluded that ENC antagonizes the estrogenic effects of ZUC on the uterus but that the beneficial effects of CLO on nonreproductive tissues in OVX'd rats is conferred by both isomers. Furthermore, the combined actions of the two isomers on bone volume and architecture were more beneficial than either isomer given alone.

Animals↗

Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial.

At present, it is unclear what the role is of laparoscopic ovarian diathermy (LOD) and of metformin administration as second-line treatments for ovulation induction in women with polycystic ovary syndrome (PCOS) after failure of clomiphene citrate (CC) treatment. The aim of the present study was to compare in a randomized double-blind placebo-controlled fashion the effectiveness of LOD with metformin administration in the treatment of CC-resistant women with PCOS. A total of 120 overweight primary infertile anovulatory CC-resistant women with PCOS were enrolled and randomized into two groups of treatment. Group A underwent diagnostic laparoscopy, whereas group B underwent LOD. At hospital discharge, the patients were treated for 6 months with metformin cloridrate (group A; 850 mg twice daily) or with multivitamins (group B). The ovulation, pregnancy, abortion, and live-birth rates were evaluated. At the end of the study, the total ovulation rate was not statistically different between both treatment groups (54.8 vs. 53.2% [correction] in groups A and B, respectively), whereas the pregnancy (21.8 [correction] vs. 13.4%), the abortion (9.3 [correction] vs. 29.0%), and the live-birth (86.0 [correction] vs. 64.5%) rates were significantly (P < 0.05) different between the two groups. Our data show that metformin administration is more effective than LOD in overall reproductive outcomes in overweight infertile CC-resistant women with PCOS.

Adult↗

Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.

CONTEXT: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. OBJECTIVE: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. DESIGN: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. SETTING: The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy. PATIENTS: One hundred nonobese primary infertile anovulatory women with PCOS participated. INTERVENTIONS: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. MEAN OUTCOME MEASURES: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. RESULTS: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001). CONCLUSIONS: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

Adult↗

Pituitary-gonadal response to acute I.M. stimulation with clomiphene citrate in normal men.

In order to asses the effect of acute i.m. injection of clomiphene citrate (CC) on LH, FSH, and testosterone (T) secretion, five normal, fertile men received 5 mg of the drug dissolved in 2 ml 0.9% saline, while a further five were injected 10 mg of the same preparation. All tests were performed at 8 a.m. Blood samples were drawn at 0, 30, 60, 120 and 180 minutes of the injection. Serum LH, FSH, and T values were determined by the double antibody radioimmunoassay technique. A significant rise of the LH, FSH, and T levels was obtained in both groups. Peak LH values were obtained at 30 minutes (average), whereas FSH and T peaks occurred at 60 minutes. The 180-minute values were similar to basal. The results seem to indicate that intramsucularly administered CC could be useful, as a rapid test, in evaluating the function of the hypothalamic-pituitary-gonadal axis.

Adult↗

Ovulation induction in clomiphene-resistant anovulatory women: differential follicular response to purified urinary follicle-stimulating hormone (FSH) versus purified urinary FSH and luteinizing hormone.

We studied 15 anovulatory women undergoing ovulation induction with purified human urinary FSH or purified human urinary FSH and LH [human menopausal gonadotropins (hMG)]. All patients had either sporadic or no vaginal bleeding after progesterone therapy and failed to ovulate after receiving clomiphene (250 mg for 5 days) plus hCG. Other causes of infertility were ruled out. Sixteen cycles of FSH and 12 cycles of hMG were administered according to a standard protocol. Estradiol, progesterone, androstenedione, testosterone, LH, and FSH concentrations were quantitated by RIA. Follicular diameter was determined using ultrasound. There was no significant difference in the amount of FSH or hMG used per patient, in the duration of therapy before hCG administration, or in the length of the luteal phase in any patient. There was a difference in the number of follicles greater than 1000 mm3 per cycle in those patients receiving FSH compared to the number in those receiving hMG [2.8 +/- 1.3 (+/- SEM) vs. 4.4 +/- 1.5 follicles; P = 0.026). The maximum follicular phase serum estradiol (18.3 vs. 34.8 ng/ml) and maximum luteal phase progesterone concentrations (1289 vs. 2808 pg/ml; P = 0.026) were also different between the FSH and hMG groups. Linear regression analysis revealed a significant correlation between the peripheral serum estradiol levels and the total follicular volume of follicles in the hMG-treated group which was not apparent in the FSH-treated group. These findings suggest that exogenous LH may not be required to induce folliculogenesis in anovulatory patients.

Adult↗

Evidence for a hypothalamic site of action of clomiphene citrate in women.

To examine the site of action of clomiphene citrate (CC), LH and FSH pulsatile amplitude, frequency, and responsiveness to GnRH (10 micrograms, iv) were studied in 11 women during the early follicular phase of the menstrual cycle. Six women received CC (150 mg/day) on cycle days 2, 3, and 4, while 5 women received placebo tablets. Blood samples were drawn at 10-min intervals for 8 h before and after the treatment regimen on cycle days 2 and 5, respectively. All women treated with CC had multiple follicular development, as determined by ultrasound. Peripheral levels of estradiol did not change after CC treatment, while progesterone levels decreased slightly. Mean levels of LH increased from 7.5 +/- 0.9 (+/- SEM) to 10.7 +/- 1.4 mIU/ml (P less than 0.05), and FSH increased from 6.7 +/- 0.9 to 10.1 +/- 0.9 mIU/ml (P less than 0.01). After exposure to CC, the pulse frequency of LH during an 8-h period increased significantly (3.3 +/- 0.7 on day 2 vs. 6.8 +/- 0.8 on day 5; P less than 0.01), while the pulse frequency of FSH increased from 3.8 +/- 0.6 to 5 +/- 1.4, as determined by computer pulse analyses. The pulse amplitude of LH and FSH was not significantly altered. In the placebo-treated group, neither pulse amplitude nor pulse frequency changed significantly between cycle days 2 and 5. Pituitary sensitivity to exogenous GnRH did not change after CC treatment. Since the pulsatile frequency of LH is governed by hypothalamic influences, these findings provide compelling evidence for a hypothalamic site of action for CC, probably by inducing an increase in the frequency of GnRH secretion.

Adult↗

Serum bioactive and immunoreactive follicle-stimulating hormone levels and the response to clomiphene in healthy young and elderly men.

Testicular function declines with normal aging, while serum immunoreactive LH and FSH levels increase. Since there are reports of an age-related decrease in the ratio of bioactivity to immunoreactivity (B/I ratio) for LH, we used a newly available bioassay for FSH to assess age-associated changes in the bioactivity and B/I ratio of FSH in man. Thirty-nine healthy men (23 young and 16 elderly) had single blood samples drawn. In addition, a subset of these men (12 young and 13 elderly) underwent frequent blood sampling for 24 h, both before and after 7 days of clomiphene citrate (CC) administration. Hourly blood samples from the 24-h sampling were pooled, and these, along with the single samples, were assayed for FSH by an in vitro bioassay system, using estrogen production by immature rat granulosa cells as the end point, and by RIA. Baseline single sample mean FSH, as measured by bioassay, was similar in young and elderly men [386 +/- 98 (+/- SEM) and 342 +/- 77 ng/mL, respectively]. Baseline mean FSH, measured by RIA, was significantly higher (P less than 0.001) in elderly men (234 +/- 31 ng/mL) than in young men (122 +/- 12 ng/mL). The baseline FSH B/I ratio based on single sampling was significantly lower (P less than 0.01) in elderly men (1.4 +/- 0.2) than in young men (2.7 +/- 0.3). In the men given CC and sampled for 24 h, mean bioactive FSH levels increased significantly in both the young (1180 +/- 282 ng/mL) and the elderly (992 +/- 227 ng/mL; P less than 0.01 for both values compared to baseline). Mean FSH by RIA also increased to similar levels in these young (217 +/- 34 ng/mL) and elderly (258 +/- 45 ng/mL) men. The FSH B/I ratio was 4.8 +/- 0.8 in young and 4.7 +/- 1.1 in elderly men after CC administration. We conclude that serum bioactive FSH levels are similar in elderly and young men, suggesting that the age-related decline in testicular function in man cannot be explained by a chronic deficiency in FSH stimulation; elderly men have a lower serum FSH B/I ratio than young men, which may reflect changes in the circulating form of FSH with aging; and administration of CC to young and elderly men increases both bioactive and immunoreactive serum FSH, implying preserved hypothalamic-pituitary responsiveness in the elderly.

Adult↗

Oocyte maturity and human follicular fluid prostanoids, gonadotropins, and prolactin after administration of clomiphene and pergonal.

Follicular fluid (FF) and oocytes were obtained from 130 follicles of 52 women in whom ovulation was induced with human menopausal gonadotropin (Pergonal) and clomiphene citrate. Follicular aspiration was performed 36 h after an ovulatory injection of hCG. The concentrations of LH, FSH, PRL, and the prostanoids prostaglandin E2 (PGE2), PGF2 alpha, PGI2 (as 6-oxo-PGF2 alpha), and thromboxane A2 (as TXB2) in the FF were measured by RIA and related to the degree of maturation of the oocyte-corona-cumulus complex mass (OCCC). FF obtained from follicles with immature OCCC contained significantly lower concentrations of all four prostanoids (median concentrations, picograms per mL: PGE2, 88; PGF2 alpha, 85; 6-oxo-PGF1 alpha, 40; TXB2, 50) than those with intermediate OCCC (PGE2, 175; PGF2 alpha, 325; 6-oxo-PGF1 alpha, 130; TXB2, 65) and mature OCCC (PGE2, 425; PGF2 alpha, 860; 6-oxo-PGF1 alpha, 235; TXB2, 78; all P less than 0.01). There were no significant differences between the maturity of the complexes and the concentrations of LH, FSH, or PRL. There were significant correlations between the FF concentrations of LH and FSH and those of all of the prostanoids, but not with PRL, concentrations. These results indicate that the synthesis of prostanoids in the human Graafian follicles may be modulated by gonadotropins and consolidates the view that prostanoids may play a role in human oocyte maturation and ovulation.

6-Ketoprostaglandin F1 alpha↗