High Dose of Phytoestrogens Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on the Endometrium in Patients Undergoing Intrauterine Insemination: A Randomized Trial

Unfer, Vittorio; Casini, Maria Luisa; Costabile, L; Mignosa, Marcella; Gerli, Sandro; Renzo, Gian Carlo Di

doi:10.1016/j.jsgi.2003.12.007

Cited by 54 publications

(38 citation statements)

References 54 publications

(1 reference statement)

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“…While genistein treatment was without effect on the endometrium of macaque monkeys with surgically induced menopause [35], our proposal is supported by the observation that endometrial hyperplasia was significantly more prevalent in postmenopausal women receiving soy tablets vs. a reference group that received a placebo [36]. Moreover, a recent study [37] has also shown that high dose phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium. Hence, we propose that the effects of soy isoflavones, including genistein on the endometrium is complex and requires further study.…”

Section: Discussionsupporting

confidence: 68%

The effects of dietary phytoestrogens on aromatase activity in human endometrial stromal cells

Edmunds¹,

Holloway²,

Crankshaw³

et al. 2005

Reprod. Nutr. Dev.

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-Dietary phytoestrogens have been reported to inhibit aromatase activity in placental microsomes, but the effects in the human endometrium are unknown. Aromatase, the rate-limiting enzyme in the conversion of androgens to estrogens, has recently been shown to be expressed in the endometrium of women with endometriosis and is thought to play a role in the pathophysiology of this disease. Therefore, the objective of this study was to screen dietary phytoestrogens for their ability to inhibit aromatase activity in human endometrial stromal cells (ESC) and identify potential novel therapeutic agents for the treatment of endometriosis. The inhibition of aromatase activity by direct interaction with the dietary phytoestrogens genistein, daidzein, chrysin, and naringenin was tested in a cell free assay. Furthermore, test compound effects on aromatase activity in ESC cultures were also examined. Genistein and daidzein were inactive in the human recombinant aromatase assay whereas naringenin and chrysin inhibited aromatase activity. However, genistein (1 nM to 1 mM) stimulated aromatase activity in ESC whereas other phytoestrogens had no effect. Immunopositive aromatase cells were demonstrated in genistein-treated ESC but not in untreated control cultures. Taken together, our data suggest that genistein can increase aromatase activity in ESC likely via increased enzyme expression.phytoestrogens / endometriosis / aromatase / genistein / endometrium

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Section: Discussionsupporting

confidence: 68%

The effects of dietary phytoestrogens on aromatase activity in human endometrial stromal cells

Edmunds¹,

Holloway²,

Crankshaw³

et al. 2005

Reprod. Nutr. Dev.

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“…We also did not find any significant difference between the treatment protocols. Unfer et al (19) have similarly not observed a difference regarding Doppler flow parameters between the groups receiving and those not receiving E2.…”

Section: Discussionmentioning

confidence: 87%

“…Other methods have been tried to eliminate these adverse effects that include low-dose CC use, starting CC intake on different days, starting at the early follicular phase, adding various agents, and various results have been reported (16)(17)(18). The implantation and pregnancy rates have been found to be significantly higher compared to placebo in groups receiving E2 in studies on the effect of SE on infertile patients undergoing in vitro fertilization (19). Patients undergoing induction with CC were found to demonstrate a beneficial effect of SE on ET but effects that were not significant on the endometrial blood flow and the number of prevovulatory follicles (20).…”

Section: Discussionmentioning

confidence: 99%

“…Thickness is also not the only important factor for implantation and Hosie et al (15) have shown by electron microscopic investigation of the endometrium that areas with marked cellular damage and lesions consisting of irregularly shaped cells are present on the endometrial surface and affect implantation. Unfer et al (19) have studied administering oral estrogen for 10 days in addition to CC and found no significant change in the FSH, LH and estrogen levels, while there was a significant increase in ET in the estrogen group. Another study on the association between ET and implantation measured the mean ET in those that did and did not achieve pregnancy as 10.2±2.6 mm and 8.6±3.4 mm respectively with pregnancy rates 13.3% in those with values under 7.5 mm and no pregnancies in those with values under 5 mm (3).…”

Section: Discussionmentioning

confidence: 99%

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The effect of administering vaginal estrogen to clomiphene citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained infertility

Çetinkaya¹,

Kadanali²

2012

J Turkish German Gynecol Assoc

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Objective: Clomiphene citrate (CC) has some negative effects on the endometrium. We aimed to determine the effect of vaginally administered local estrogen (LE) on endometrial thickness (ET) and pregnancy rates in CC stimulated cycles. Material and Methods:This was a prospective randomized crossover study that took place in a university hospital. The patients had received CC due to unexplained infertility (UI). Two different treatment protocols were given sequentially as, either CC+LE or CC alone. Each protocol was planned for two cycles and there was a one-month wash-out period between protocols. The effects of LE on the 3 rd and 9 th day, the ovulation day (OD) and 7 th postovulation day (POD7) were investigatedResults: A total of 6 pregnancies were achieved with 3 patients from each protocol. The ET was 7.6±1.4 mm and 8.3±2.1 mm respectively and significantly different in the CC group and the CC+E2 groups on the OD (p=.039), while these values were 9.7±2.3 mm and 10.9±3.0 mm respectively and significantly different on the POD7 (p=.007). There was no significant difference between the groups for arterial PI values on the OD and POD7. The frequency of thin endometrium (<6 mm) was 15.2% and 12.2% respectively in the CC group and the CC+E2 group on the OD (p=.628) and 5.1% and 1.2% respectively on the POD7 (p=.182). Conclusion:Adding vaginal LE to CC stimulated cycles led to a significant increase in ET on the OD and POD7. However, this difference in thickness was not reflected in the pregnancy rates in this study.

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“…They reached the conclusion that phytoestrogens administered in high doses have the ability to reverse the adverse effects of CC on endometrial thickness with contribution to higher pregnancy rates [12] . Shahin and colleagues randomly classified 134 women with unexplained infertility treated by induction of ovulation using CC into 2 equal groups.…”

Section: Discussionmentioning

confidence: 99%

Phytoestrogens as an alternative to estradiol in reversing the antiestrogenic effect of clomid on endometrium in ovulation induction in cases of PCO

Maged

Deeb

2015

Uterus Ovary

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Objective:To study the effect of phytoestrogens as an alternative to estradiol in reversing the antiestrogenic effect of clomid on endometrium in ovulation induction in cases of PCOS. Methods: Prospective study conducted on 150 women with PCOS were randomly divided using automated web based randomization system into 3 groups: group I included 50 women received CC only50 mg orally every 8 hours started from cycle day 3 for 5 days, group II included 50 women received estradiol from cycle day 7 to day 11 in addition to CC and group III included 50 women received phytoestrogen (20mg of cimifuga racemosa from day 1to12) in addition to CC. Results: There was a statistically significant difference between group I and the other two groups regarding occurrence of ovulation (82 vs.100 and 100 % respectively) A statistically significant difference was found between the three study groups regarding endometrial thickness (5.5±1.07 vs. 9.37 ±1.75 and 10.1±1.87 respectively). Also a significant difference was found between group I and the other two groups regarding pregnancy rate (18 vs.34 and 26 % respectively). Conclusion: Adding phytoestrogens to CC as an alternative to estradiol in PCOS women have increased the count of dominant follicles and improved endometrial thickness and pattern with improvement of both ovulation and pregnancy rates.

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High Dose of Phytoestrogens Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on the Endometrium in Patients Undergoing Intrauterine Insemination: A Randomized Trial

Abstract: A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.

Cited by 54 publications

References 54 publications

The effects of dietary phytoestrogens on aromatase activity in human endometrial stromal cells

The effects of dietary phytoestrogens on aromatase activity in human endometrial stromal cells

The effect of administering vaginal estrogen to clomiphene citrate stimulated cycles on endometrial thickness and pregnancy rates in unexplained infertility

Phytoestrogens as an alternative to estradiol in reversing the antiestrogenic effect of clomid on endometrium in ovulation induction in cases of PCO

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