Kuntai Capsule Combined With Letrozole on Gonadal Hormone Levels and Ovarian Function in Patients With PCOS: A Systematic Review and Meta-Analysis.

Background: The efficacy of Kuntai capsule combined with letrozole (LE) in improving ovarian function of polycystic ovary syndrome (PCOS) has been evaluated before, but there is still a lack of evidence-based support for the regulation of sex hormone levels. In recent years, new randomized clinical trials (RCTs) have been reported on the effect of combined therapy on regulating sex hormone levels. Objective: We aimed to systematically evaluate the efficacy of Kuntai capsule combined with LE in the treatment of PCOS. Methods: A search across the China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang database, PubMed, Web of Science, The Cochrane Library, and Embase was conducted on Kuntai capsule combined with LE in the treatment of PCOS. The time of the self-built database was up to April 30, 2021. RCTs of LE in the control group and LE combined with Kuntai capsule in the experimental group were selected. RevMan5.3 software was used for data analysis. Results: A total of 17 studies were gathered, which included 1,684 patients. The meta-analysis results showed that the total effective rate of the combined group was 93.36% and that of the LE group was 78.15%. The improvement in the ovulation rate, pregnancy rate, number of mature follicles, endometrial thickness, cervical mucus score, and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) in the combined group was consistent with the results of a previous meta-analysis and was better than that in the LE group (p < 0.05). In addition, the combination group was better than the LE group in regulating the levels of estradiol (E2) and testosterone (T) (p < 0.05). There were no adverse drug reactions in the two groups during treatment. Conclusion: As a type of pure traditional Chinese medicine preparation, Kuntai capsule combined with LE had a better effect than LE alone in the treatment of PCOS, with advantages mainly reflected in enhancing ovarian function and regulating the levels of sex hormones in vivo, among others, but the value of combined therapy still needs to be verified by more high-quality RCTs.

Chinese herbal medicine on treating obese women with polycystic ovary syndrome: A systematic review and meta-analysis protocol.

INTRODUCTION: Known as an endocrine disorder, Polycystic ovary syndrome (PCOS) has posed an influence on 6% to 20% reproductive females worldwide. The commonly used pharmaceutical agents currently are Oral Contraceptives (OCs) and insulin-sensitizing agents. However, OCs is not appropriate for females pursuing pregnancy. Furthermore, some of insulin-sensitizing agents are found to be related to a high incidence of gastrointestinal adverse effects. In this regard, the effectiveness of Chinese herbal medicine in handling reproductive and metabolic defects simultaneously has been proved by extensive evidence. In this research, the effectiveness and safety of Chinese herbal medicine for obese females with PCOS were examined. METHODS AND ANALYSIS: In the systematic review, we searched databases of AMED, Science Online, EMbase, WorldSciNet, the Cochrane Library, PubMed, Nature, MEDLINE, China National Knowledge Infrastructure, the Wanfang Databse and China Biology Medicine Disc and the Chongqing VIP Chinese Science and Technology Periodical Database, to find out the papers published in Chinese or English by September 25, 2020 in this field. In addition, potential reference lists, relevant conference proceedings, qualified studies, related system reviews and other resources were also considered. Two researchers were responsible for independently selecting the research papers, collecting data, and evaluating research quality. Moreover, the data were synthesized with the combination of a fixed-effects or random-effects model with the heterogeneity test. According to the objective and self-reported assessment, the primary outcomes will be Nausea and vomiting were primary outcomes. RevMan 5 software was used to analyze the collected data, the evidence level of which was evaluated by GRADE. The selection between the fixed-effects and random-effects models was determined by the heterogeneity level. In addition to the 95% Confidence Interval (CI), odds ratio (OR), or risk ratio (RR) was applied to the 2 categories. Moreover, 95% CI and standardized mean difference (SMD) or the weighted mean difference (WMD) were taken as the continuous variables. When existing meaningful heterogeneity could not be explained by any assessment such as subgroup analysis, we would not conduct a meta-analysis. During the subgroup analysis, each subgroup in specific cases should be comprehensively considered. ETHICS AND DISSEMINATION: The evaluation of rights or personal information of patients was not involved in the systematic review. Hence, we need not gain approval from ethical institutions. This paper will be present at related conferences for communication and published in journals. REGISTRATION: Open Science Framework (OSF) Preregistration: osf.io/yp86h.

The Associations Between Gonadal Hormones and Serum Uric Acid Levels in Men and Postmenopausal Women With Diabetes.

Introduction: In assessing the development of hyperuricemia in diabetic adults, the role of the sex steroid axis is underappreciated. Furthermore, dehydroepiandrosterone (DHEA) has been recommended as a nutritional supplement. However, is DHEA suitable for diabetic adults with hyperuricemia? This issue has received little attention. Aim: The objective of this study was to investigate the associations between gonadal hormones and uric acid (UA) levels in diabetic adults, paying particular attention to the association between DHEA and UA levels. Methods: We analyzed 4,426 participants out of 4,813 diabetic adults enrolled from seven communities in a cross-sectional survey conducted in 2018. Participants underwent several examinations, including assessments of anthropometric parameters, blood pressure, glucose, lipid profiles, UA, total testosterone (TT), estradiol (E2), the follicle-stimulating hormone (FSH), the luteinizing hormone (LH), and dehydroepiandrosterone (DHEA). Results: Among men and compared with individuals in the first quartile, participants in the fourth quartile of TT and FSH had odds of hyperuricemia that were significantly decreased by so much as 48 and 34%, respectively (both P < 0.05). However, participants in the fourth quartile of DHEA had 79% increased odds of hyperuricemia (P < 0.05). Among postmenopausal women, participants in the fourth quartile of DHEA, TT, and LH had odds of hyperuricemia that were significantly increased by 155, 99, and 76%, respectively (all P < 0.05). These associations were adjusted for potential confounding factors. Conclusions: Sex differences were found in the associations between gonadal hormones and UA levels in diabetic men and postmenopausal women, which should be monitored to prevent hyperuricemia when sex hormone treatment, especially DHEA, is administered. Further studies are needed.

Adverse reproductive effects of ethanolic root extract of Waltheria indica in male Wistar rats.

Background Numerous uses of Waltheria indica plant such as antitrypanosomal, antibacterial and antimalarial effects have been reported. It has however been reported that most plants with antibacterial and antiprotozoal effects have adverse effect on male reproduction. Hence, we evaluated the effect of Waltheria indica root on male reproductive parameters. Methods Twenty adult male Wistar rats were randomly divided into four groups (n=5); A-D. Group A served as control group while groups B, C and D were administered with 200, 400 and 800 mg/Kg body weight of crude ethanolic extract of Waltheria indica root. After 28 days of administration, the rats were sacrificed and sperm parameters, sperm morphology, serum reproductive hormones and lipids were determined. Results There was a significant reduction in sperm count and motility as well as significant increase in percentage abnormal sperm cell (p<0.001) at the 400 and 800 mg/kg BW. The serum levels of testosterone was also significantly reduced while total cholesterol increased significantly (p<0.05) at the highest dose. Conclusion Waltheria indica root has adverse effect on male reproduction through reduction in sperm parameters and male reproductive hormones.

[Effects of Yishen Shengjing Capsules on semen quality and gonadal hormone levels in rats with dibutyl phthalate-induced reproductive function injury].

OBJECTIVE: To study the possible pathogenesis of infertility caused by dibutyl phthalate (DBP) and investigate the effects of Yishen Shengjing Capsules (YSC, kidney-tonifying and essence-producing capsules) on DBP-induced reproductive function injury and its possible action mechanisms in male Wistar rats. METHODS: Models of DBP-induced reproductive function injury were made in 80 male Wistar rats and another 20 were used as blank controls. After modeling, the model rats were randomly divided into a model control, a high-dose YSC, a medium-dose YSC, and a low-dose YSC group. Four weeks after intervention, all the animals were sacrified for observation of the histomorphologic changes in the testis under the light microscope, measurement of sperm concentration, motility and abnormality, and determination of the levels of serum testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by radioimmunoassay. RESULTS: Compared with the blank controls, the model rats showed obvious pathological changes in testicular histomorphology, significantly decreased sperm concentration and motility, increased sperm abnormality, reduced contents of serum T and LH, and elevated the level of serum FSH (P<0.01). After 4 weeks of medication, the animals of the high-, medium-, and low-dose YSC groups, in comparison with the model controls, exhibited different degrees of recovery from testicular histomorphological damage, remarkably increased sperm concentration and motility, decreased sperm abnormality, elevated levels of serum T and LH, and reduced content of serum FSH (P<0.01). There were statistically significant differences in all the parameters above between the high-dose YSC and medium- and low-dose YSC groups (P<0.01). CONCLUSIONS: DBP reduces sperm motility and concentration, increases sperm abnormality, causes damage to the morphological structure of the rat testis, decreases the contents of serum T and LH, and elevates the level of the serum FSH. Yishen Shengjing Capsules can improve DBP-induced productive function injury, increase sperm motility and concentration, decrease sperm abnormality, elevate the level of serum T and LH, reduce the content of serum FSH, improve the morphological structure of the testis, and thus promote the reproductive function of the male rat.

Aphrodisiac effect of aqueous root extract of Lecaniodiscus cupanioides in sexually impaired rats.

BACKGROUND: The phytochemical constituents of the aqueous root extract of Lecaniodiscus cupanioides Planch. Ex Bth. and its aphrodisiac activity on male rat sexual behavior and reproductive hormones in paroxetine-induced sexual dysfunction were evaluated. METHODS: The extract was screened for the presence of phytochemicals. The extract (25, 50, and 100 mg/kg body weight) and the reference herbal drug PowmaxM (7.14 mg/kg body weight) were administered orally to paroxetine-induced sexually impaired male rats, once daily for 5 days, and their sexual behavior parameters were monitored and computed. The serum hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone) were determined at the end of treatment period. RESULTS: Phytochemical screening revealed the presence of alkaloids, anthraquinones, phenolics, saponins, and tannins. Mount frequency (MF), intromission frequency (IF), ejaculatory frequency (EF), and testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations were reduced significantly (p<0.05) in paroxetine-treated rats. Administration of 25, 50, and 100 mg/kg body weight of the aqueous root extract of L. cupanioides significantly (p<0.05) reversed the paroxetine-mediated alterations in MF, IF, EF, mount latency (ML), intromission latency (IL), ejaculatory latency (EL), postejaculatory interval (PEI), and testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations dose-dependently. The reversal of the male sexual behavior parameters by the extract compared well (p<0.05) with the PowmaxM-treated animals. CONCLUSIONS: Data obtained from this study revealed that the aqueous root extract of L. cupanioides restored sexual competence in sexually impaired rats possibly by increasing sexual drive through enhanced reproductive hormones concentration, particularly testosterone, thus supporting the folkloric claim of the plant for the management of sexual disorder in males.

The impact of an aromatase inhibitor on body composition and gonadal hormone levels in women with breast cancer.

Aromatase inhibitors (AIs) have become the standard adjuvant therapy of postmenopausal breast cancer survivors. AIs induce a reduction of bioavailable estrogens by inhibiting aromatase, which would be expected to induce alterations in body composition, more extensive than induced by menopause. The objectives are to examine the impact of AIs on (1) DXA-scan derived body composition and (2) gonadal hormone levels. This is a sub-analysis of a 2-year double-blind, placebo-controlled, randomized trial of 82 women with nonmetastatic breast cancer, newly menopausal following chemotherapy, who were randomized to risedronate (35 mg once weekly) versus placebo, and stratified for their usage of AI versus no AI. Outcomes included DXA-scan derived body composition and gonadal hormone levels. As a group, total body mass increased in women over 24 months. Women on AIs gained a significant amount of lean body mass compared to baseline as well as to no-AI users (P < 0.05). Women not on an AI gained total body fat compared to baseline and AI users (P < 0.05). Free testosterone significantly increased and sex hormone binding globulin (SHBG) significantly decreased in women on AIs compared to no AIs at 24 months (P < 0.01) while total estradiol and testosterone levels remained stable. Independent of AI usage, chemotherapy-induced postmenopausal breast cancer patients demonstrated an increase of total body mass. AI users demonstrated maintenance of total body fat, an increase in lean body mass and free testosterone levels, and a decrease in SHBG levels compared to no-AI users. The mechanisms and implications of these changes need to be studied further.

[The effectiveness of transcranial treatment using the AMO-ATOS-E apparatus for the correction of the reproductive system disorders in adolescent girls].

A combination of transcranial therapy and transcranial electrostimulation based on the use of the AMO-ATOS-E apparatus was applied to elucidate the hormonal status and to study lipid and carbohydrate metabolism in 84 girls of pubertal age. The correction of menstrual cycles in these patients brought about its normalization in 86.3% of the cases with the simultaneous reduction of their body weight by 9.26 +/- 4.28 kg during 3 months.

[Study on the underlying mechanism of acupuncture in regulating neuroendocrine activity in dysmenorrhea rats].

OBJECTIVE: To observe the influence of acupuncture on neuroendocrine in rats with primary dysmenorrhea, so as to explore its underlying mechanism in relieving dysmenorrhea. METHODS: Forty female Wistar rats were equal randomized into control, model, acupuncture and Extractum Leonuri Inspissatum (ELI) groups, with 10 cases in each. Primary dysmenorrhea model was established by intragastric perfusion of diethylstilbestrol (3 mg/kg), once daily for 12 days. "Guanyuan" (CV 4), bilateral "Sanyinjiao" (SP 6) and "Diji" (SP 8) were punctured once daily for 7 days. ELI (80 g/kg) was given to rats of ELI group via gastrogavage, once daily for 7 days. On the 12th day, the rats of 4 groups were given with oxytocin (14 U/kg, i.p.) for inducing dysmenorrhea. The latency and incidence rate of writhing within 30 min were observed. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) were detected by radioimmunoassay, and the expression of gonadotropin-releasing hormone (GnRH) mRNA in hypothalamus and ovary, GnRH receptor (GnRH-R) mRNA in pituitary, estrodiol receptor (ER) mRNA and progesterone receptor (PR) mRNA in uterus were determined using RT-PCR. RESULTS: After modeling, the writhing latency shortened considerably and the writhing times, serum FSH, LH and E2 levels increased apparently, and serum P content decreased markedly (P<0.05). Compared with model group, the writhing times, serum FSH, LH, and E2 contents in acupuncture and ELI groups reduced significantly (P<0.05), while the writhing latency and serum P contents in acupuncture and ELI groups increased remarkably (P<0.05). Compared with control group, hypothalamic GnRH mRNA, ovary GnRH mRNA, pituitary GnRH-R mRNA and uterus ER mRNA expressions in model group were up-regulated significantly, while uterus PR mRNA was down-regulated markedly in model group (P<0.05). In comparison with model group, hypothalamic GnRH mRNA, ovary GnRH mRNA, pituitary GnRH-R mRNA and uterus ER mRNA expressions in acupuncture and ELI groups were suppressed significantly (P<0.05), while uterus PR mRNA expressions in the later two groups were up-regulated obviously (P<0.05). CONCLUSION: Acupuncture of CV4, SP6 and SP8 can effectively relieve dysmenorrhea in the rat, which may be closely related to its effects in regulating neuroendocrine activities and the related receptor expression of hypothalamus-pituitary-ovary axis.

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

PURPOSE: To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). PATIENTS AND METHODS: Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. RESULTS: Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. CONCLUSION: Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Manganese acts centrally to activate reproductive hormone secretion and pubertal development in male rats.

Manganese (Mn) is an important element for normal growth and reproduction. Because Mn accumulates in the hypothalamus and is capable of stimulating puberty-related hormones in female rats, we assessed whether this metal could cause similar effects in male rats. We have demonstrated that MnCl2, when administered acutely into the third ventricle of the brain, acts dose dependently to stimulate luteinizing hormone (LH) release. Furthermore, there was a dose dependent stimulation in the secretion of LH-releasing hormone (LHRH) from the medial basal hypothalamus in vitro, and administration of an LHRH receptor antagonist in vivo blocks Mn-induced LH release. To assess potential chronic effects of the metal, male pups were supplemented with 10 or 25 mg MnCl2 per kg by gastric gavage from day 15 until days 48 or 55, at which times developmental signs of spermatogenesis were assessed. Results demonstrate that while significant effects were not observed with the 10 mg/kg dose, the animals receiving the 25 mg/kg dose showed increased LH (p<0.05), FSH (p<0.01) and testosterone (p<0.01) levels at 55 days of age. Furthermore, there was a concomitant increase in both daily sperm production (p<0.05) and efficiency of spermatogenesis (p<0.05), demonstrating a Mn-induced acceleration in spermatogenesis. Our results suggest Mn is a stimulator of prepubertal LHRH/LH secretion and may facilitate the normal onset of male puberty. These data also suggest that the metal may contribute to male precocious pubertal development should an individual be exposed to low but elevated levels of Mn too early in life.

Short-term soy and probiotic supplementation does not markedly affect concentrations of reproductive hormones in postmenopausal women with and without histories of breast cancer.

BACKGROUND: Observational studies suggest that dietary isoflavones reduce breast cancer risk, and this may be caused in part by effects on endogenous hormone concentrations. Because intestinal bacteria metabolize isoflavones, it was hypothesized that consumption of probiotic bacteria would enhance the biologic effects of isoflavones, including effects on endogenous hormones. DESIGN: Twenty (20) postmenopausal breast cancer survivors and 20 healthy postmenopausal women completed four 42-day diet periods in a randomized, crossover design. They received one of the following: isolated soy protein; isolated milk protein; soy + probiotic capsules; or milk + probiotic capsules. Each protein supplement provided 0.38 g protein/(kg body weight/day) (26.6 +/- 4.5 g protein/day) and soy protein provided 0.64 mg isoflavones/(kg body weight/day) (44.4 +/- 7.5 mg isoflavones/day). Probiotic capsules provided 10(9) colony-forming units Lactobacillus acidophilus (strain DDS-1), Bifidobacterium longum, and 15-20 mg fructo-oligosaccharide. MEASURES: Plasma samples were collected at baseline and after each diet for analysis of estrogens, follicle-stimulating hormone (FSH), androgens, and sex hormone?binding globulin (SHBG). RESULTS: Hormone levels were not affected by soy, probiotic supplements, or equol producer status, and neither cancer status nor equol producer status altered the effects of soy or probiotics. Furthermore probiotics did not alter the effects of soy consumption. Soy protein tended to decrease SHBG compared to milk protein diets (p = 0.05), although both proteins significantly decreased SHBG relative to baseline (p = 0.0001 and p = 0.03). CONCLUSIONS: These data suggest that short-term, moderate consumption of isoflavone-containing soy protein and consumption of these particular probiotic capsules do not significantly alter reproductive hormone concentrations in breast cancer survivors or controls, regardless of equol producer status.