Modulatory effects of R10 fraction of garlic (Allium sativum L.) on hormonal levels, T cell polarization, and fertility-related genes in mice model of polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is an inflammatory endocrine-metabolic disorder related to reproductive system characterized by polycystic ovarian morphology, androgen excess, and chronic anovulation. Current treatments haven’t been very successful in PCOS treatment and the problem still remains as a challenge. Therefore, new approaches should be applied to overcome the disease. Previous studies demonstrated immunomodulatory effects of R10 fraction of garlic in the treatment of inflammatory conditions such as cancer. Considering previous studies suggesting immunomodulatory therapy for PCOS, therapeutic effects of R10 fraction was evaluated in a mouse model of PCOS. To do so, PCOS was developed by intramuscular injection of estradiol valerate. Treatment with R10 fraction, isolated from garlic, was performed and the alterations in hormonal levels (estradiol, progesterone, and testosterone), T cell polarization markers (IFN-γ, IL-4, and IL-17), and expression of fertility-related genes (Gpx3 and Ptx3) were evaluated. The results showed that hormonal levels were elevated in PCOS model comparing to normal animals but were markedly modulated after treatment with R10 fraction. Moreover, a severe disturbance in T cell polarization with a significant reduction of fertility-related genes expression were detected in PCOS-induced ovaries. Treatment with R10 fraction also represented modulatory effects on T cell polarization by increasing IL-4 and decreasing IL-17 and IFN-γ levels. Accordingly, fertility-related genes were also modulated following treatment with R10 fraction in PCOS. Our study elucidated that R10 fraction of garlic possess immunomodulatory effects alleviating PCOS symptoms. This approach could be adjusted to give rise the optimum therapeutic results and considered as a candidate therapeutic approach for PCOS.

Challenges in Establishing a Relevant Model of Polycystic Ovary Syndrome in Rats – A Mini Review

Polycystic ovary syndrome (PCOS) is one of the most com-mon female endocrinopathy and one of the leading causes of in-fertility. However, the exact etiopathogenetic mechanisms are not discovered yet, while therapeutic strategies in PCOS commonly rely on symptomatic rather than curative. Regarding reasonable ethical limitations in human population, animal experimental studies can provide better insights into mechanisms underlying etiopathogenesis of PCOS, as well as investigations of different therapeutic strategies. Rodent models for PCOS are very useful for experimental studies due to their great genetic similarities with human genome, short reproductive and life span, feasible gener-ating of genetically adapted animals, and convenient and acces-sible use. To our knowledge, androgens (dehydroepiandroste-rone, testosterone propionate, 5a-dihydrotestosterone), as well as estradiol valerate, represent the most frequently used hormones for PCOS modeling. Furthermore, the administration of antipro-gesterone or letrozole has been reported as effective for PCOS induction. In our review, the presented PCOS models were ac-complished by the administration of different hormones or drugs and alterations of environment. The main focus of this review was to summarize the alterations in ovarian morphology, hypotha-lamic-pituitary-ovarian axis, and hormone levels across above-mentioned protocols for postnatal PCOS modeling in rats.

A study of comparison of effectiveness of letrozole (5mg) versus clomephene citrate (100 mg) for ovulation induction among infertile women

Clomiphene citrate has been traditionally used as the drug of the choice for treatment of women with anovulatory infertility. In the last decade, an aromatase inhibitor, letrozole has emerged as an alternative ovulation induction agent among anovulatory women with polycystic ovarian syndrome. Letrozole has a definitive role in anovulatory women who have not responded to the clomiphene citrate therapy is confirmed by literatures. Anovulatory dysfunction is a common problem and is responsible for about 40% of female infertility and among causes; PCOS (polycystic ovarian syndrome) is the leading cause. Clomiphene citrate is considered as the drug of choice for the first line treatment of anovulatory dysfunction for a variety of reasons. Clomiphene citrate has some side effects like multi-follicular development and cyst formation and resistance of clomiphene are areas of concern and desire for an effective alternative persists.An aromatase inhibitor, letrozole, was introduced into infertility practice in the year 2000 and is regarded as a second line option, particularly in women with clomiphene resistance, and it has found acceptance in various clinical situations and the indications for use have expanded., To compare the efficacy of letrozole and clomiphene citrate (CC) for ovulation induction in infertile women. The study included 100 women presented with anovulatory infertility. The infertile women were divided into 2 groups of 50: Group A received 100 mg Clomiphene Citrate from day 3 to day 5 of menstruation and Estradiol Valerate 4 mg on the 12 day of menstruation until 16 day of menstruation; Group B treated by 5 mg Letrozole from day 3 to day 5 of the menstruation and as Group A, Estradiol Valerate 4 mg on the 12 day of menstruation until 16 day of menstruation given to Group B, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. Participants were of 20 to 39 years age, had normal uterine cavity and had a male partner with a sperm concentration of at least 14 million per millilitre; and during the study the women and their partners agreed to have regular intercourse with the intent of conception. The live birth during the treatment period was the primary outcome. Women who received letrozole had more cumulative live births than those women who had received clomiphene citrate (36 out of 50 [72%] vs. 28 out of 50 [56%]), without significant differences in overall congenital anomalies, there were no congenital anomalies. With letrozole as compared to clomiphene the cumulative ovulation rate was higher. Higher incidence of hot flushes was associated with a clomiphene, and letrozole was associated with fatigue and dizziness. Rates of other adverse effects were almost similar among these 2 groups. A significant difference in the follicular and endometrial development was evident among these 2 groups. As compared to with clomiphene, an aromatase inhibitor, letrozole was associated with higher live-birth and ovulation rates among infertile women. The results of the study demonstrated letrozole to be superior to clomiphene citrate in the maintenance of endometrial thickness.

A high dose of estrogen can improve renal ischemia-reperfusion-induced pulmonary injury in ovariectomized female rats

Renal ischemia-reperfusion injury (RIRI) as a pathological process induces remote organ injury such as lung complications and it is regulated in a hormone-dependent manner. This study investigates the effect of estrogen on RIR-induced pulmonary injury in ovariectomized (OV) rats. A total of 60 female Wistar rats were divided into six groups: (i) intact sham, (ii) OV sham, (iii) OV sham + estradiol valerate (E), (iv) intact ischemia, (v) OV ischemia, and (vi) OV ischemia + E. Bilateral ischemia was performed for 45 min in all groups except sham. Before the ischemia, OV groups received an intramuscular (i.m.) injection of E. After reperfusion, blood samples were collected for serum analysis and kidney and lung tissue were separated for pathological experiment and malondialdehyde (MDA) and nitrite measurement. The left lung was weighed to measure pulmonary edema. Estrogen deficiency caused a greater increase in blood urea nitrogen and creatinine levels during IRI. Ischemia reduced nitrite of serum and lung tissue. The increased level of MDA during ischemia, returned to normal levels via estrogen injection. The severity of renal and lung damage in ischemic groups increased significantly, and estrogen improved this injury. Estrogen as an antioxidant agent can reduce oxidative stress and may improve renal function and ameliorating lung damage caused by RIR.

Appropriate Age for Height Control Treatment in Patients With Marfan Syndrome

ObjectiveThis study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS).Materials and MethodsThis retrospective study included patients with MFS who underwent height control treatment with estradiol valerate. The estrogen dose was increased according to the height change. The cut-off age for the maximum difference between the expected height and actual final height was evaluated.ResultsSeventeen patients were included in this study. The difference between the height predicted by the growth curve and the final height (gcHtD) and that predicted by the bone age and the final height (baHtD) was the largest in the 10.5 years age group (p=0.0045 and p=0.0237, respectively). The gcHtD was 10.6 (10.2, 13.5) cm for patients aged ≤10.5 years, whereas it was 0.6 (−3.65, 5.85) cm for patients aged >10.5 years. The baHtD was 10.1 (7.31, 11.42) cm for patients aged ≤10.5 years, while it was 3.83 (0.84, 6.4) cm for patients aged >10.5 years. When height change was observed for a minimum of 6 months after completion of estrogen treatment, the average growth was 0.6 (0.2, 2.1) cm.ConclusionInitiating height control treatment before the age of 10.5 years is effective in female patients with MFS.

A Clinical Study of the Effect of Estradiol Valerate on Sleep Disorders, Negative Emotions, and Quality of Life in Perimenopausal Women

In this prospective study, we randomly divided 100 patients with perimenopausal syndrome equally into the control group (n = 50) receiving conventional treatment and the study group (n = 50) receiving estradiol valerate. The indicators observed were endometrial thickness, uterine volume, and the levels of LH (luteinizing hormone), FSH (follicle-stimulating hormone), and E2 (estradiol) of the patients before and after treatment. The Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety/Depression Scale (HAMA/HAMD), Kupperman symptom score, and menopause-specific quality of life (MENQOL) were also applied to assess the sleep quality, negative emotions, severity of the condition, and quality of life of all patients, respectively. Our findings were that estradiol valerate is beneficial in improving serum sex hormone levels, sleep disturbances, negative mood, and quality of life in patients with perimenopausal syndrome and that its safety profile is high enough to warrant clinical promotion.

Effects of early estradiol valerate administration on bone turnover markers in surgically induced menopausal women

Background Compared with a natural process, surgically induced menopausal women have a higher bone loss rate. This study aims to evaluate early treatment with estradiol valerate on bone turnover markers after surgically induced menopause. Methods This prospective study included 41 pre and perimenopausal women who underwent hysterectomy with oophorectomy for benign gynecologic conditions. Two weeks after the operation, all participants were assessed for menopausal hormone therapy (MHT) indications. Estrogen therapy was prescribed for those who had indications and accepted treatment (hormone treatment group). The others who had no MHT indication were allocated to the no-treatment group. Serum CTX and P1NP levels at preoperative and 12 weeks postoperative were measured and set as the primary outcome. Within the same group, serum CTX and P1NP before and after surgical menopause were analyzed using Wilcoxon signed-rank test. ANCOVA was used to compare serum CTX and P1NP at 12 weeks after surgical menopause between the two groups. Spearman's rank correlation coefficient analysis analyzed the correlation between age and baseline bone turnover markers. A p-value of < 0.05 was considered statistically significant. Results At 12 weeks after surgery, there were no significant differences in serum CTX and P1NP levels in the hormone treatment group compared to baseline. In contrast, serum CTX and P1NP levels were significantly elevated among women who did not receive hormone treatment (p-value < 0.001 and 0.002, respectively). Serum CTX and P1NP at 12 weeks were significantly different between the two groups (p-value < 0.001 and 0.004, respectively). Conclusion Early estrogen administration with oral estradiol valerate could significantly suppress the high bone remodeling in surgically induced menopausal women. Trial registration Thai Clinical Trial Registry identification number TCTR20190808004, retrospective registered since 2019-08-08. http://www.thaiclinicaltrials.org/show/TCTR20190808004.