BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents.
METHODS: The current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman-Gallwey score) levels were evaluated before and after the study.
RESULTS: Data from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p < 0.001), right (p = 0.002), and left (p = 0.010) ovarian volume, serum LH (p < 0.001) and testosterone (p = 0.001) were significantly higher in the intervention group compared to the control group. The frequency of oligomenorrhea, menometrorrhagia, and amenorrhea, were significantly reduced after the study in the intervention group compared to the control group (ps < 0.001).
CONCLUSIONS: Short-term Nigella sativa supplementation may be effective in reducing ovarian volume and improving hormonal balance, and menstrual irregularities in adolescents with PCOS. Further research and long-term studies are warranted to validate the potential therapeutic effects of Nigella sativa in adolescents with PCOS.
UNASSIGNED: IRCT20221017056209N1 Registration date: 2022-11-22.

The objective of this study was to examine the current trends in fertility-sparing (FS) treatment for young atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) patients in Japan.
This study was conducted by the Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology (JSOG) in the 2017-2018 fiscal year. A nationwide, retrospective questionnaire-style survey-as performed. We collected the data of 413 patients from 102 JSOG gynecological cancer registered institutions.
FS treatment was performed with medroxyprogesterone (MPA) (87.2%) or MPA + metformin (11.6%). Pathological complete remission (CR) after initial treatment was achieved in 78.2% of patients. The significant clinicopathological factors correlated to CR after initial treatment were histology (AEH vs. endometrioid carcinoma grade 1 [ECG1]), body mass index (BMI) (<25 vs. ≥25 kg/m²), and treatment period (<6 vs. ≥6 months). ECG1, time to complete remission (TTCR) ≥6 months, maintenance therapy (-), and pregnancy (-) were associated with a significantly higher risk of recurrence on multivariate analysis. The total pregnancy rate was 47%, and the live birth rate was 40.1%. Patients who received infertility treatments showed a higher live birth rate (50.6%) than those who did not (7.7%).
In this survey, we confirmed that FS treatment in Japan is centered on MPA alone and in combination with metformin, and that the treatment efficacy is similar to that reported in previous reports. A multicenter survey study in Japan showed FS treatment for young AEH and EC patients in compliance with the indications is feasible.

UNASSIGNED: The purpose of this study was to evaluate the impact of isoflavone supplementation compared with placebo on endometrial histology and serum estradiol levels in premenopausal women with nonatypical endometrial hyperplasia.
UNASSIGNED: The present double-blindplacebo-controlled clinical trial was conducted on 100 women with nonatypical endometrial hyperplasia in the age range of 30 to 45 years. Participants were randomly assigned to receive 50 mg of isoflavone (n = 50) or placebos (n = 50) daily for three months. Both groups received the standard treatment of nonatypical endometrial hyperplasia. Endometrial biopsy and blood samples were taken at the baseline and three months after the intervention. The incidence of drug side effects was assessed as well.
UNASSIGNED: After three months, 88.4% of isoflavone-administered subjects had a significant histological improvement compared to 68.9% subjects in the placebo group (P=0.02). There were no significant differences between the two groups in the changes of serum estradiol levels and the incidence of drug side effects.
UNASSIGNED: The findings of the present study demonstrated that the coadministration of 50 mg of isoflavones and medroxyprogesterone acetate increases the treatment efficacy in women with nonatypical endometrial hyperplasia. Clinical Trial Registration. This trial was registered on the Iranian website for clinical trial registration (https://www.irct.ir/trial/53553).

Sickle cell disease (SCD) is associated with altered plasma and erythrocyte lipid profiles. In a previous study, SCD mice with deficiency of proprotein convertase subtilisin/kexin type 9 (PCSK9) were observed to have more severe anemia and increased sickling compared to control SCD mice. Although PCSK9 affects circulating low density lipoprotein (LDL) by regulation of the LDL receptor, the effect of PCSK9 on anemia was independent of LDL receptor expression. In the current study, erythrocyte metabolomics were performed and revealed altered erythrocyte lipid species between SCD mice with and without PCSK9. Of particular interest, the late endosome-specific lipid bis(mono)acylglycerol phosphate (BMP) 44:12 was markedly decreased in erythrocytes from SCD mice deficient in PCSK9 mice relative to control SCD mice. Incubation of sickle erythrocytes with a neutralizing antibody to BMP increased erythrocyte sickling in vitro. In vitro treatment of SCD erythrocytes with amiodarone (1.5 μM) or medroxyprogesterone (6.75 μM), two pharmacologic compounds known to increase BMP, resulted in reduced erythrocyte sickling. Treatment of SCD mice with amiodarone (10 mg/kg) for 2 weeks resulted in increased BMP, improvement in anemia with reduced reticulocytosis, and decreased ex vivo sickling. In conclusion, severity of anemia in SCD is improved with amiodarone treatment, an effect which may be mediated through increased erythrocyte BMP.

Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.
We conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.
Of participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).
Recent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.

UNASSIGNED: Endometriosis is a chronic inflammatory gynecological disorder that causes pelvic pain. Due to the heterogeneity of the disease, response to any treatment in an individual is variable. We aimed to develop in vitro testing that could be adapted for use in precision therapy for endometriosis. We piloted a personalized medicine approach by identifying predictive biomarkers while determining the effect of bazedoxifene (BZA) and medroxyprogesterone acetate (MPA) on the gene expression of a progesterone receptor (PR), an estrogen receptor (ER), and an aromatase (CYP19A1) enzyme in cells cultured from biopsies of endometriosis patients. The differential expression of the most common molecular targets in endometriosis therapy correlated with cellular response.
UNASSIGNED: Primary eutopic endometrial stromal cells were cultured from endometrial biopsies obtained in secretory phase from women between 24 and 42 years old with moderate-to-severe endometriosis (stages III and IV). Exclusion criteria included use of hormonal treatments and intrauterine contraception in the 6 months prior to surgery. Cells were treated either with BZA, MPA, or vehicle control. Total RNA was extracted from the treated and untreated cells. Differential expression of genes that are involved in the pathogenesis of endometriosis was determined by quantitative reverse transcriptase-polymerase chain reaction analysis.
UNASSIGNED: After determining the baseline expression levels of PRA/B, ERα and CYP19A1, response to treatment was monitored using Ki-67 as a marker of cell proliferation. MPA was effective in blocking proliferation in the group expressing high levels of PRA/B. Endometrium expressing high levels of CYP19A1 preferentially responded to BZA, a selective estrogen receptor modulator known to block estrogen action in endometrium.
UNASSIGNED: PR expression may predict progestin resistance in endometriosis while CYP19A1 expression may indicate the need to block estrogen signaling.

Background: Medroxyprogesterone and donepezil could be used as respiratory stimulants in ventilated patients. However, no randomized placebo-controlled trial is available to confirm this approach and compare these drugs. The aim of the current study was to evaluate the effects of donepezil or medroxyprogesterone compared to the placebo in improvement in respiratory status and weaning facilitation in critically ill adult patients receiving mechanical ventilation. Material and Methods: This randomized, triple-blind trial was conducted on 78 ventilated patients in intensive care units (ICU). Patients who were intubated due to pulmonary disorders were ruled out. Patients were randomized in a 1:1:1 ratio to receive 5 mg donepezil (n = 23) or 5 mg medroxyprogesterone (n = 26), or placebo (n = 24) twice a day until weaning (maximum 10 days). The primary endpoints were weaning duration, and duration of invasive mechanical ventilation. Secondary endpoints included rate of successful weaning, changes in arterial blood gas (ABG) parameters, GCS and sequential organ failure assessment (SOFA) score, hemoglobin (Hgb), ICU-mortality, and duration of ICU stay, were measured before and after the intervention and if successful weaning was recorded. Results: Of 78 studied patients who were randomized, 59 weaned successfully. 87% patients in donepezil and 88.5% patients in medroxyprogesterone groups were successfully weaned compared to 66.7% patients in the placebo group. However, this difference was not statistically significant (p-Value = 0.111). Changes in pH, mean duration of intubation, and weaning duration were statistically different in donepezil compared with the control group (p-Value < 0.05). No significant difference in ABG, Hgb, GCS and SOFA score, and duration of intubation were seen in the medroxyprogesterone group, but weaning duration was significantly reduced to 1.429 days compared with the control group (p-Value = 0.038). Conclusion: The results of this clinical trial have demonstrated that the administered dose of medroxyprogesterone and donepezil can expedite the weaning process by reducing the weaning duration compared to placebo. Furthermore, the total duration of invasive ventilation was significantly lower in the donepezil group compared to the control group. Future clinical trials with a larger sample size will determine the exact role of medroxyprogesterone and donepezil in mechanically ventilated patients. Clinical Trial Registration: https://irct.ir/IRCT20190810044500N2 (April 1, 2020).

UNASSIGNED: To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR).
UNASSIGNED: This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates.
UNASSIGNED: In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% vs. 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% vs. 29.6%, P=0.14).
UNASSIGNED: For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.

We evaluated if alternative treatments achieve at least similar results as traditional long treatments with intravaginal sponges (IVS) in three experiments considering (1) the use of 6-day treatments associated or not with the administration of PGF2alpha at IVS insertion; (2) a reduction of 50% MAP content in short-term or traditional treatments, with or without change of the IVS 6 days after its insertion; and (3) the substitution of IVS for long-time acting injected progesterone associated with the administration of a PGF2alpha. More ewes came into estrus with long than short IVS treatments, independently of the MAP IVS content. Fewer ewes came into estrus if the IVS containing 30 mg was replaced 6 days after its insertion. The length of the treatment did not affect the conception rate, but the pregnancy rate was greater in 12 than 6 days treatments. The administration of long-acting progesterone did not prevent the lower conception rate associated with the use of PGF2alpha and was less effective to synchronize estrus, but the conception rate did not differ from that of 12d IVS treatments. Overall, MAP content could be decreased without affecting the estrous rate; thereafter, the MAP IVS content should be decreased in the commercial devices. Although pregnancy rate was lower using long-acting injected progesterone than with IVS, as the conception rate did not differ, it is interesting to study deeper the use of this treatment, especially if preparations of progesterone with a longer half-life are developed. However considering all the results, the traditional long IVS treatment still provided the best result.

Depot Medroxyprogesterone (DMPA) is one of the most widely used contraceptives in Sub-Saharan Africa where HIV incidence is high. We explored the effect of DMPA on the activation of HIV cellular targets and inflammation as a possible mechanism of increased HIV risk with DMPA use. Since sex work is known to affect the immune system, this study aimed to understand the effect of DMPA on the immune system among sex workers and non-sex worker women.
Twenty-seven DMPA-using HIV seronegative female sex workers (FSW) and 30 DMPA-using HIV seronegative non-sex worker (SW) women were enrolled in the study. Twenty-four FSWs and 30 non-sex workers who were not using any hormonal contraception (no HC) were recruited as controls. Blood and cervico-vaginal samples were collected from all participants and assayed for T cell activation and proinflammatory cytokines.
Among no HC users, sex workers had lower expression of CD38 and CD69 on blood-derived CD4+ T cells along with lower CD4+CCR5+ cells frequency in the endocervix. Plasma MCP-1, TNFα and IL-17 also had reduced expression in FSW not using HC. Non-sex workers using DMPA had elevated proportions of blood-derived CD4+CD38+, CD4+CD69+ and CD4+HLA-DR+ T cells relative to non-sex workers who were not taking any HC. DMPA-using non-sex workers also had an increased level of plasma interferon gamma (IFN-γ), monokine induced by interferon-γ (MIG) and sCD40L, alongside higher proportion of CD4+CD38+ and CD4+CD69+ T cells at the cervix compared to non-sex workers no-HC controls., Finally, non-sex workers and FSWs using DMPA had similar levels of genital and peripheral CD4+ T cell activation and inflammation.
DMPA increased inflammation and expression of activation markers on potential HIV target cells in non-sex workers. These data show that DMPA is a strong immune modulator and its use counteracts the decreased immune activation associated with sex work. These findings suggest that inflammation and increased HIV target cells in blood and at the genital tract may be mechanisms by which DMPA increases susceptibility to HIV.