Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis.

BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. METHODS The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. RESULTS Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by approximately 20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones ( approximately 14%, SMD, P = 0.07, 21 studies). CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined.

Probiotic capsules do not lower plasma lipids in young women and men.

OBJECTIVE: To investigate the effect of probiotic capsules on plasma lipids. DESIGN: A randomized, single-blinded, placebo-controlled, parallel-arm trial. SUBJECTS: Fifty-five normocholesterolemic subjects ages 18-36 (33 premenopausal women and 22 men). INTERVENTION: Each subject consumed either three probiotic capsules each containing a total of 10(9) colony-forming units Lactobacillus acidophilus and Bifidobacterium longum and 10-15 mg fructo-oligosaccharide or three placebo capsules daily for 2 months (men) or two menstrual cycles (women). Plasma lipids were measured before and following the intervention (during the early follicular phase for women). RESULTS: Plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride were not altered by consumption of probiotic or placebo capsules and were not different between treatment groups following the intervention. CONCLUSIONS: These results do not support a beneficial effect of Lactobacillus acidophilus strain DDS-1 and Bifidobacterium longum strain UABL-14 on plasma lipids in normocholesterolemic young women and men. SPONSORSHIP: Supported by the Minnesota Agricultural Experiment Station and UAS Laboratories.

Consumption of Lactobacillus acidophilus and Bifidobacterium longum do not alter urinary equol excretion and plasma reproductive hormones in premenopausal women.

OBJECTIVE: To confirm the results of an earlier study showing premenopausal equol excretors to have hormone profiles associated with reduced breast cancer risk, and to investigate whether equol excretion status and plasma hormone concentrations can be influenced by consumption of probiotics. DESIGN: A randomized, single-blinded, placebo-controlled, parallel-arm trial. SUBJECTS: In all, 34 of the initially enrolled 37 subjects completed all requirements. INTERVENTION: All subjects were followed for two full menstrual cycles and the first seven days of a third cycle. During menstrual cycle 1, plasma concentrations of estradiol (E(2)), estrone (E(1)), estrone-sulfate (E(1)-S), testosterone (T), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) were measured on cycle day 2, 3, or 4, and urinary equol measured on day 7 after a 4-day soy challenge. Subjects then received either probiotic capsules (containing Lactobacillus acidophilus and Bifidobacterium longum) or placebo capsules through day 7 of menstrual cycle 3, at which time both the plasma hormone concentrations and the post-soy challenge urinary equol measurements were repeated. RESULTS: During menstrual cycle 1, equol excretors and non-excretors were not significantly different with respect to subject characteristics, diet, or hormone concentrations. Significant inverse correlations were found between E(2) and body mass index (BMI) (P=0.02), SHBG and BMI (P=0.01), DHEA-S and dietary fiber (P=0.04), and A and protein:carbohydrate ratio (P=0.02). Probiotic consumption failed to significantly alter equol excretor status or hormone concentrations during menstrual cycle 3, although there were trends towards decreased concentrations of T (P=0.14) and SHBG (P=0.10) in the probiotic group. CONCLUSIONS: We were unable to verify a previously reported finding of premenopausal equol excretors having plasma hormone concentrations different from those of nonexcretors. Furthermore, a 2-month intervention with probiotic capsules did not significantly alter equol excretion or plasma hormone concentrations.

Clinical outcomes following interval laparoscopic transabdominal cervico-isthmic cerclage placement: case series.

The purpose of this report is to describe outcomes following laparoscopic transabdominal cervico-isthmic cerclage placement in cases of cervical incompetence not amenable to a conventional transvaginal procedure. We reviewed records of the first 11 patients at an academic teaching hospital who underwent laparoscopic transabdominal cerclage placement as an interval procedure, using a technique we previously first described. For all patients, the clinical course, including surgical complications and outcome of all subsequent pregnancies, is briefly described. One case was complicated by a small bowel injury secondary to concomitant extensive enterolysis. Otherwise there were no complications. Mean estimated blood loss was <40 ml. To date, 10 patients have conceived a total of 12 pregnancies following the procedure. Two pregnancies resulted in spontaneous losses at 8 weeks gestation, two in deliveries by Caesarean section at 34.5 weeks, and eight in deliveries by elective Caesarean section at 38 weeks or more. Each delivery resulted in the birth of a healthy infant. In conclusion, patients who require a transabdominal cerclage may undergo a laparoscopic interval procedure and achieve outcomes similar to those following placement via laparotomy during pregnancy.

Lack of effect of isoflavonic phytoestrogen intake on leptin concentrations in premenopausal and postmenopausal women.

OBJECTIVE: To assess the effect of soy isoflavone ingestion on plasma leptin concentrations in premenopausal and postmenopausal women. DESIGN: Randomized, crossover studies, with blinding of participants and laboratory personnel. SETTING: Procedures involving free-living individuals were carried out at the University of Minnesota General Clinical Research Center. PATIENT(S): Fourteen regularly cycling premenopausal women, and 18 postmenopausal women. INTERVENTION(S): Each premenopausal participant consumed, on a daily basis, each of three soy protein powders containing different levels of isoflavones for three menstrual cycles plus 9 days, with plasma samples collected every other day the last 6 weeks of each diet period. Similarly, each postmenopausal participant consumed each of the three powders for 93 days, with plasma samples collected daily on days 64 to 66 and 92 to 94 of each diet period. The powders, dosed on a per-kilogram body weight basis, provided mean isoflavone intakes of 8, 65, and 130 mg/day, for the control, low-isoflavone, and high-isoflavone diet periods, respectively. MAIN OUTCOME MEASURE(S): Plasma leptin concentrations. RESULT(S): Isoflavone intake had essentially no effect on leptin concentrations in either premenopausal or postmenopausal participants. Concentrations in the premenopausal women were higher during the periovulatory and midluteal phases as compared to the early follicular and midfollicular phases. CONCLUSION(S): Despite the well-documented effect of estrogens to enhance leptin production, even high levels of isoflavone consumption do not alter leptin concentrations in women. Further studies are needed to more precisely delineate the nature of estrogenic and/or antiestrogenic effects of isoflavones in humans.

Polycystic ovary syndrome and ovulation induction.

Before initiating treatment to induce ovulation in cases of PCOS, an appropriate evaluation of the patient and her partner, based on individual considerations, is important to optimize outcome. For obese patients with PCOS, weight-loss measures should be pursued before pharmacologic treatment is initiated. For most patients, the pharmacologic agent of choice to induce ovulation is clomiphene citrate, alone or in combination with a glucocorticoid. Treatment with metformin, alone or in combination with clomiphene citrate, may also be beneficial. For patients not responsive to clomiphene citrate, injectable gonadotropin treatment is usually warranted, although, depending on individual circumstances, laparoscopic ovarian drilling may be appropriate.

Initial IVF-ET experience with assisted hatching performed 3 days after retrieval followed by day 5 embryo transfer.

OBJECTIVE: To report our initial IVF-ET experience combining assisted hatching performed 3 days after oocyte retrieval with day 5 embryo transfer (ET). DESIGN: Retrospective review of 110 consecutive IVF cycles not involving donor oocytes, including 16 cycles that involved assisted hatching performed 3 days after oocyte retrieval in combination with day 5 ET. SETTING: Academic teaching hospital IVF center. PATIENT(S): Eighty-six consecutive IVF patients undergoing ET. INTERVENTION(S): Assisted hatching using acid Tyrode's solution performed 3 days after oocyte retrieval in selected cases in combination with day 3 or 5 ETs. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per ET. RESULT(S): Of the 16 women undergoing day 5 ET following day 3 assisted hatching, 14 had a clinical pregnancy. These included 11 ongoing/delivered singletons and 2 ongoing/delivered twin pregnancies, neither of which was monochorionic. These clinical and ongoing/delivered pregnancy rates compared very favorably with those of 54% and 46%, respectively, for the 35 patients undergoing day 5 ETs without assisted hatching, even though the latter group appeared to be better IVF candidates based on the prognostic factors commonly used to predict success. CONCLUSION(S): Our experience suggests that day 3 assisted hatching followed by day 5 ET may be a useful combination in selected patients. Although not seen in our small series, an increased risk of monochorionic pregnancies remains a theoretical concern when such a combination is used, since both assisted hatching and blastocyst transfers have been independently linked to an increased risk in some reports.

Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women.

Soy isoflavones are hypothesized to exert hormonal effects in women and thus may play a role in bone metabolism throughout life. In 2 randomized, cross-over studies, 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [control, 0.13; low isoflavone (low-iso), 1.00; and high-iso, 2.01 mg/kg body wt/day, averaging 8, 65, and 130 mg/day, respectively], for over 3 months each. Food records, blood samples, and 24-h urine collections were obtained throughout the studies. The endpoints evaluated included plasma or serum concentrations of bone-specific alkaline phosphatase, osteocalcin, insulin-like growth factor-I (IGFI), IGF binding protein-3 (IGFBP3), and urine concentrations of deoxypyridinoline cross-links and carboxy-terminal telopeptide of type I collagen. In premenopausal women, IGFI and IGFBP3 concentrations were increased by the low-iso diet, and deoxypyridinoline cross-links was increased by both the low- and high-iso diets during certain phases of the menstrual cycle. In postmenopausal women, bone-specific alkaline phosphatase was decreased by both the low- and high-iso diets, and there were trends toward decreased osteocalcin, IGFI, and IGFBP3 concentrations with increasing isoflavone consumption. Although soy isoflavones do affect markers of bone turnover, the changes observed were of small magnitude and not likely to be clinically relevant. These data do not support the hypothesis that dietary isoflavones per se exert beneficial effects on bone turnover in women.

Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer.

Increased urinary excretion of equol, a metabolite of the isoflavone daidzein, has been associated with a reduced risk of breast cancer. This risk reduction has generally been presumed to be a consequence of increased isoflavone consumption. However, only 30-40% of the population excretes more than trace amounts of equol, regardless of isoflavone intake. Accordingly, we hypothesized that the observed apparent protective effect of equol is at least in part attributable to hormonal differences between equol excretors and non-excretors, and that these differences are largely independent of isoflavone intake. We measured plasma hormone and sex hormone binding globulin (SHBG) concentrations in 14 normally cycling premenopausal women during each of three diet periods in which they consumed differing isoflavone doses (0.15, 1.0, and 2.0 mg/kg of body weight/day) as a component of soy protein isolate. The plasma hormone and SHBG concentrations of equol excretors (n = 5) were then compared with those of the non-excretors (n = 9). Results showed that even at the lowest dose, urinary equol excretion values for excretors far exceeded those for non-excretors consuming the highest dose. At all doses, equol excretors generally had lower concentrations of estrone, estrone-sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulfate, and cortisol and higher concentrations of SHBG and midluteal progesterone, a hormonal pattern overall consistent with lowered breast cancer risk. In conclusion, the association of equol excretion and lowered breast cancer risk may largely reflect the tendency of equol excretors to have more favorable hormonal profiles, as opposed to merely reflecting increased isoflavone intake. Equol may be a marker for the presence of colonic bacterial enzymatic activity that increases fecal steroid excretion. Alternatively, equol itself, even with very modest isoflavone intake, may exert beneficial effects on the regulation of endogenous hormones.

Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women.

BACKGROUND: Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear. OBJECTIVE: The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women. DESIGN: Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase. RESULTS: Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002). CONCLUSIONS: Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.

Menstrual cycle effects on urinary estrogen metabolites.

Endogenous estrogen metabolism may play an important role in the pathogenesis of hormone-related cancers, most notably breast cancer. Despite the importance of estrogen metabolism, little is known about estrogen metabolite profiles during different phases of the menstrual cycle. This study was performed to evaluate the effects of the menstrual cycle on endogenous estrogen metabolism. Twenty-four-hour urine samples were collected daily during 4 precisely defined phases of the menstrual cycle (early follicular, midfollicular, periovulatory, and midluteal phases) from 6 healthy premenopausal women. Urine samples were analyzed for 15 endogenous estrogens and their metabolites by an ion exchange chromatography and the capillary gas chromatography-mass spectrometry method. The patterns of urinary estrogen metabolites (including potentially genotoxic 16alpha-hydroxyestrone, 4-hydroxyestradiol, and 4-hydroxyestrone) followed those of plasma estradiol and estrone, showing significant increases in the periovulatory and midluteal phases. Compared to the early and midfollicular phases, the ratios of 2-hydroxyestrogens/16alpha-hydroxyestrogens and 2-hydroxyestrogens/4-hydroxyestrogens were significantly increased during the periovulatory and midluteal phases (by 28% and 72%, respectively; P < 0.05), suggesting that estrogen metabolism is significantly affected by menstrual cycle phase. These data indicate that menstrual cycle phase must be considered in studies of estrogen metabolism in premenopausal women.

Modest hormonal effects of soy isoflavones in postmenopausal women.

Soy isoflavones have been hypothesized to exert hormonal effects in postmenopausal women. To test this hypothesis, we studied the effects of three soy powders containing different levels of isoflavones in 18 postmenopausal women. Isoflavones were consumed relative to bodyweight [control: 0.11 +/- 0.01; low isoflavone (low-iso): 1.00 +/- 0.01; high isoflavone (high-iso): 2.00 +/- 0.02 mg/kg/day] for 93 days each in a randomized crossover design. Blood was collected on day 1 of the study (baseline) and days 36-38, 64-66, and 92-94 of each diet period, for analysis of estrogens, androgens, gonadotropins, sex hormone binding globulin (SHBG), prolactin, insulin, cortisol, and thyroid hormones. Vaginal cytology specimens were obtained at baseline and at the end of each diet period, and endometrial biopsies were performed at baseline and at the end of the high-iso diet period, to provide additional measures of estrogen action. Overall, compared with the control diet, the effects of the low-iso and high-iso diets were modest in degree. The high-iso diet resulted in a small but significant decrease in estrone-sulfate (E1-S), a trend toward lower estradiol (E2) and estrone (E1), and a small but significant increase in SHBG. For the other hormones, the few significant changes noted were also small and probably not of physiological importance. There were no significant effects of the low-iso or high-iso diets on vaginal cytology or endometrial biopsy results. These data suggest that effects of isoflavones on plasma hormones per se are not significant mechanisms by which soy consumption may exert estrogen-like effects in postmenopausal women. These data also show that neither isoflavones nor soy exert clinically important estrogenic effects on vaginal epithelium or endometrium.

Soy isoflavones exert modest hormonal effects in premenopausal women.

Soy isoflavones are hypothesized to be responsible for changes in hormone action associated with reduced breast cancer risk. To test this hypothesis, we studied the effects of isoflavone consumption in 14 premenopausal women. Isoflavones were consumed in soy protein powders and provided relative to body weight (control diet, 10 +/- 1.1; low isoflavone diet, 64 +/- 9.2; high isoflavone diet, 128 +/- 16 mg/day) for three menstrual cycles plus 9 days in a randomized cross-over design. During the last 6 weeks of each diet period, plasma was collected every other day for analysis of estrogens, progesterone, LH, and FSH. Diet effects were assessed during each of four distinctly defined menstrual cycle phases. Plasma from the early follicular phase was analyzed for androgens, cortisol, thyroid hormones, insulin, PRL, and sex hormone-binding globulin. The low isoflavone diet decreased LH (P = 0.009) and FSH (P = 0.04) levels during the periovulatory phase. The high isoflavone diet decreased free T3 (P = 0.02) and dehydroepiandrosterone sulfate (P = 0.02) levels during the early follicular phase and estrone levels during the midfollicular phase (P = 0.02). No other significant changes were observed in hormone concentrations or in the length of the menstrual cycle, follicular phase, or luteal phase. Endometrial biopsies performed in the luteal phase of cycle 3 of each diet period revealed no effect of isoflavone consumption on histological dating. These data suggest that effects on plasma hormones and the menstrual cycle are not likely to be the primary mechanisms by which isoflavones may prevent cancer in premenopausal women.

Effect of the menstrual cycle on creatinine clearance in normally cycling women.

OBJECTIVE: We assessed changes in creatinine clearance during the menstrual cycle of normally cycling women. METHODS: We used a design that precisely identified the day of ovulation. Creatinine clearance was measured in 14 subjects on each of three days: cycle day 2 or 3, 1 or 2 days before the day of ovulation, and 6 or 7 days after ovulation. RESULTS: Creatinine clearance was affected significantly by the menstrual cycle (P=.02), but the degree of this effect was modest. Mean (+/-standard error of mean) early follicular, preovulatory, and midluteal creatinine clearance values were 135+/-4, 131+/-5, and 142+/-5 mL/min, respectively, and only the difference between the preovulatory and midluteal values was significant. These changes in creatinine clearance were attributable largely to changes in creatinine excretion and not to changes in plasma creatinine concentrations. CONCLUSION: Despite the statistically significant luteal phase increase, creatinine clearance does not change in a clinically important manner during the normal menstrual cycle. Specifically, there is no substantial decrease in creatinine clearance around the time of ovulation.

Laparoscopic transabdominal cervicoisthmic cerclage.

OBJECTIVE: To report a laparoscopic technique for placement of a transabdominal cervicoisthmic cerclage. DESIGN: Detailed case report of one of three patients undergoing described procedure. SETTING: University hospital. PATIENT: A 39-year-old infertile patient with a history of cervical adenocarcinoma in situ and two cone biopsies, resulting in an essentially absent exocervix. INTERVENTION(S): Laparoscopic transabdominal cervicoisthmic cerclage placement, as an interval procedure, followed by ET of cryopreserved donor oocyte-derived embryos. MAIN OUTCOME MEASURE(S): Clinical outcome. RESULT(S): Establishment of a pregnancy delivered at 38 1/2 weeks of gestation by elective cesarean section. CONCLUSION(S): Patients believed to require a transabdominal cerclage may undergo a laparoscopic interval procedure, obviating the need for a laparotomy before or during pregnancy.

Use of recombinant human follicle-stimulating hormone for in vitro fertilization-embryo transfer after severe systemic immunoglobulin E-mediated reaction to urofollitropin.

OBJECTIVE: To report the successful use of recombinant human FSH in a patient with a history of a severe systemic immunoglobulin E (IgE)-mediated reaction to urofollitropin. SETTING: University hospital. PATIENT: A 38-year-old infertility patient who had experienced a whole-body rash with hives, tachycardia, fever, and other symptoms after urofollitropin administration, with confirmation of IgE-mediated sensitivity to urofollitropin by intradermal skin testing. INTERVENTION: In vitro fertilization-ET after the use of recombinant human FSH to stimulate ovarian follicular development. RESULTS: Establishment of a clinical pregnancy. CONCLUSIONS: Our case provides evidence for the involvement of nongonadotropin proteins as the direct cause of some adverse reactions from conventional urine-derived human FSH preparations.

Presentation of a müllerian anomaly with outflow obstruction after tubal ligation.

OBJECTIVE: To report an unusual presentation of a patient with unicornuate uterus and a noncommunicating functional rudimentary horn and discuss related patient management issues. SETTING: University hospital. PATIENT: A 27-year-old woman who presented with cyclic abdominal pain after a postpartum tubal ligation. INTERVENTION: Diagnostic studies followed by a laparotomy and resection of the rudimentary horn. RESULTS: Resolution of patient's symptoms. CONCLUSIONS: Patients with a unicornuate uterus and a rudimentary horn recognized for the first time during a tubal ligation require individualized management depending in part on the precise nature of the horn.

A prospective comparison of Synthetic Serum Substitute and human serum albumin in culture for in vitro fertilization-embryo transfer.

OBJECTIVE: To compare the efficacy of a globulin-containing protein source, Synthetic Serum Substitute (Irvine Scientific, Santa Ana, CA) and human serum albumin (HSA) in the early culture of human oocytes and embryos. DESIGN: Oocytes from 31 consecutive IVF cycles were assigned alternately to dishes containing human tubal fluid (HTF) and either Synthetic Serum Substitute or HSA as the protein source. Each semen sample was split for processing in Synthetic Serum Substitute or HSA. Sperm processed in Synthetic Serum Substitute was added to oocytes cultured in Synthetic Serum Substitute, and sperm processed in HSA was added to oocytes cultured in HSA. After determination of fertilization, zygotes were placed in HTF containing the same protein supplement. Before transfer, the embryos were graded morphologically. MAIN OUTCOME MEASURES: Occurrence of normal fertilization and embryo quality as assessed by morphological grading. RESULTS: There was no significant difference in the occurrence of fertilization or in embryo morphological quality between oocytes cultured in Synthetic Serum Substitute as compared with HSA. CONCLUSIONS: The use of a globulin-containing protein source in culture for IVF-ET did not improve the fertilization rate or embryo quality. Our design did not allow for demonstration of an effect on pregnancy rate.