William R. Phipps

Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women

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 ∼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 (∼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.

Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience

OBJECTIVE To present the experience of a large referral center with patients with the rare but specific syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. DESIGN, PATIENTS Between 1953 and 1991, 15 patients with the syndrome were evaluated by the authors; each patients records were carefully reviewed. MAIN OUTCOME MEASURES For each patient, the clinical course, specific anatomic findings, treatment(s) offered, and obstetrical outcome are presented. RESULTS The specificity of the association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was confirmed by our series, the largest in the literature to date. The findings suggest a specific development anomaly of the müllerian ductal system, probably secondary to a wolffian duct anomaly. The most common clinical presentation was that of the onset of pelvic pain and/or dysmenorrhea shortly after menarche, in association with the finding of a vaginal/pelvic mass. When a communication between the two sides existed, symptoms of abnormal vaginal discharge and bleeding were common. Optimal outcome appears to have occurred for patients initially managed using a conservative surgical approach, i.e., simple vaginal septum resection combined with conservative treatment of associated endometriosis. Obstetrical outcome in our patients was similar to that in patients with the more common combination of uterus didelphys and sagittal vaginal septum. CONCLUSION A greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis, allowing for early and appropriate surgical intervention as well as decreased long-term morbidity.

Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis

OBJECTIVE To determine whether isoflavones exert estrogen-like effects in men by lowering bioavailable T through evaluation of the effects of soy protein or isoflavone intake on T, sex hormone-binding globulin (SHBG), free T, and free androgen index (FAI) in men. DESIGN PubMed and CAB Abstracts databases were searched through July 1, 2008, with use of controlled vocabulary specific to the databases, such as soy, isoflavones, genistein, phytoestrogens, red clover, androgen, testosterone, and SHBG. Peer-reviewed studies published in English were selected if [1] adult men consumed soy foods, isolated soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating T, SHBG, free T, or calculated FAI was assessed. Data were extracted by two independent reviewers. Isoflavone exposure was abstracted directly from studies. MAIN OUTCOME MEASURE(S) Fifteen placebo-controlled treatment groups with baseline and ending measures were analyzed. In addition, 32 reports involving 36 treatment groups were assessed in simpler models to ascertain the results. RESULT(S) No significant effects of soy protein or isoflavone intake on T, SHBG, free T, or FAI were detected regardless of statistical model. CONCLUSION(S) The results of this meta-analysis suggest that neither soy foods nor isoflavone supplements alter measures of bioavailable T concentrations in men.

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 109 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.

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.

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 (E2), estrone (E1), estrone-sulfate (E1-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 E2 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.

Epidermal growth factor in human follicular fluid stimulates mouse oocyte maturation in vitro

OBJECTIVE To study the effect of human follicular fluid (FF) and the specific contribution of its epidermal growth factor (EGF) component on the in vitro maturation of cumulus-enclosed mouse oocytes. DESIGN A previously described mouse oocyte model system was used to study the effect of FF on oocyte maturation before and after extraction of EGF by immunoprecipitation. Follicular fluid specimens enclosing both mature and immature human oocytes were tested. MAIN OUTCOME MEASURES The endpoints assessed were the percentage of oocytes undergoing germinal vesicle breakdown (GVBD) and polar body one formation at different intervals over a 24-hour period and the final degree of cumulus expansion achieved. RESULTS A concentration-related stimulatory effect of mature FF was noted when compared with the spontaneous increase of GVBD and polar body one formation observed for the EGF-free control medium. Overall, the effect of immature FF was inhibitory. After extraction of EGF from FF by immunoprecipitation from both immature and mature FF, the rates of GVBD and polar body one formation were decreased in both groups. The addition of 5 ng/mL of EGF to the extracted groups reversed this effect on polar body one formation. Cumulus expansion was maximal for oocytes incubated with mature FF and minimal for those incubated with EGF-free media. CONCLUSIONS The positive effect of mature human FF on mouse oocyte maturation and cumulus expansion is to a large extent because of the presence of EGF.

Type of oral contraceptive in relation to acute initial episodes of pelvic inflammatory disease

A case-control analysis of hospital-based data was conducted to evaluate whether low-dose combination oral contraceptives (OCs) protect against pelvic inflammatory disease (PID). Other categories of combination OCs based on estrogen dose were also assessed. The results indicate no OC confers protection if taken for less than 12 months. In contrast, the education-adjusted relative risk (RR) estimates for continuous exposure of greater than or equal to 12 months for various categories of combination OCs based on estrogen dose all ranged from 0.2 to 0.4 with overlapping 95% confidence intervals (CIs); however, the adjusted RR for low-dose pills was not statistically significant (RR = 0.4, 95% CI: 0.2, 1.1). These data are consistent with the hypothesis that low-dose estrogen pills as well as higher dose estrogen OCs potentially protect against PID requiring hospitalization. Low-dose estrogen combination OCs deserve further study in relation to PID generally, and more particularly, in regard to specific microorganisms causing PID.

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.

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 Tyrodes 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.