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.

OBJECTIVE: Hormonal treatment is the preferred initial systemic therapy for patients with advanced or recurrent G1 or G2 endometrial cancer (EC) in terms of efficacy, toxicity, and economy. Few reports are available on the topic and we, therefore, conducted a retrospective study.
METHODS: Patients with EC who received high-dose medroxyprogesterone (MPA) at our Hospital between January 2010 and December 2022 were reviewed. Patients who were treated for fertility preservation or had a history of systemic chemotherapy other than adjuvant therapy were excluded.
RESULTS: Sixteen patients who were eligible for study inclusion had recurrent G1 or G2 EC. Their median age was 65 years (range=51-82 years), median body mass index was 22.6 kg/m2 (range=15.3-43.2 kg/m2), and all patients had an ECOG Performance Status of 0. All patients received 200 mg/day of MPA, and eight patients concomitantly received 100 mg/day of aspirin. None of the patients experienced severe adverse events. One patient had grade 2 deep vein thrombosis. Two patients discontinued MPA treatment because of adverse events. The response rate was 44% [95% confidence interval (CI)=20-68%] and median progression-free survival (PFS) was 6.9 months (95% CI=7.5-26 months). Four of 16 patients had PFS longer than 12 months, all of whom had positive tissue estrogen receptor (ER) and progesterone receptor (PR), and PFS at 2 years was 35% (95% CI=10.2-59.8%).
CONCLUSIONS: Hormone therapy is effective long-term in ER- and PR-positive EC and can be recommended as initial systemic therapy. Toxicity is mild and manageable.

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).

BACKGROUND: Only old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment.
METHODS: This was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan-Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate.
RESULTS: From the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer.
CONCLUSIONS: In actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.

This study aimed to improve the knowledge of low-grade endometrial stromal sarcoma (LG-ESS) with intracaval or intracardiac extension and tried to identify the potential risk factors and optimal treatment method influencing prognosis.
We performed a retrospective review of eight LG-ESS patients with intracaval or intracardiac extension who underwent treatment at Peking Union Medical College Hospital between 2012 and 2020.
The median age at diagnosis was 44 years, ranging from 28 to 56 years. Abnormal uterine bleeding was the most common intimal symptom (3/8), followed by low back discomfort (2/8), edema of the lower limbs (2/8), abdominal pain (1/8), and dyspnea (1/8). All patients underwent resection of the intravascular and extravascular portions of the tumor. Two patients were in stage IIIC, and six were in stage IVB. After surgery, four patients received adjuvant radiotherapy, of whom three also received letrozole. One patient was treated with letrozole alone, and one patient received medroxyprogesterone. The average follow-up time was 34.5 months, ranging from 6 to 98 months. No patients died or relapsed during the follow-up period.
LG-ESS with intracaval or intracardiac extension is an uncommon type of tumor which is easily misdiagnosed and can only be diagnosed by histological evaluation after surgery. Complete tumoral excision followed by adjuvant therapy may benefit patient survival time. Long-term follow-up is essential due to the high rate of late recurrence.

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).

Several tissue clearing methods have been developed for three-dimensional imaging of thick specimens. Here, we applied CUBIC and ScaleS approaches to whole-mounted vaginal wall to reveal spatial distribution of γδ T lymphocytes, the key cells engaged in the epithelial homeostasis control and immune surveillance. Both methods rendered the tissue transparent and enabled detection of the green fluorescent protein (GFP)-expressing γδ T cells in vaginal samples of Tcrd-H2BeGFP transgenic mice. Upon additional immunolabeling, however, only CUBIC preserved the GFP signal and allowed for cell localization assessment during the estrous cycle. Using a combination of single- and two-photon microscopy, we found that during the diestrus phase the number of γδ T cells in the vaginal wall increased compared to estrus, while the proportion of cells residing in epithelium and stroma remained constant, irrespective of the cycle phase, and was close to 3:1, respectively. Moreover, the distance from epithelial γδ T cells to laminin-positive basal membrane and collagen-rich stroma also increased in diestrus in spite of thinning of epithelium upon shedding cornified cells. Our data indicate that γδ T cells sense sex hormone fluxes which influence their number and position them closer to the vaginal lumen in the diestrus phase.

To investigate whether risk of relapse of endometrial hyperplasia persists many years after successful primary therapy and whether clinical or biological markers observed at primary diagnosis may predict relapse.
A series of 57 women with endometrial hyperplasia received levonorgestrel-impregnated intrauterine system or oral progestin for three months during 1998-2000. Index biopsies were classified according to WHO1994 and D-score systems, and immunohistochemical staining for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor A (PRA), progesterone receptor B (PRB), B-cell lymphoma 2/apoptosis regulator (BCL2), BCL2-associated X protein/apoptosis regulator (BAX), paired box 2 (PAX2), and phosphatase and tensin homolog (PTEN) reported as H-scores.
Over a follow-up of 157.8 months, 23% (10/43) of patients experienced relapse. No correlation with age, body mass index, parity, WHO94 classification, or D-score was found. Only PRA (p=0.004) and PRB (p=0.038) showed certain correlation with relapse.
Endometrial hyperplasia recurs many years after successful progestin therapy. Increased expression of PRB and reduced expression of PRA significantly correlated with relapse. Our results support the importance of continuous endometrial protection and the need for new clinical surveillance guidelines.

Medroxyprogesterone acetate is widely used in veterinary medicine as intravaginal dosage for the synchronization of breeding cycle in ewes and goats. The main goal of this study was to develop reverse-phase high-performance liquid chromatography method for the quantification of medroxyprogesterone acetate in veterinary vaginal sponges. A single high-performance liquid chromatography/UV isocratic run was used for the analytical assay of the active ingredient medroxyprogesterone. The chromatographic system consisted of a reverse-phase C18 column as the stationary phase and a mixture of 60% acetonitrile and 40% potassium dihydrogen phosphate buffer as the mobile phase; the pH was adjusted to 5.6. The method was validated according to the International Council for Harmonisation (ICH) guidelines. Forced degradation studies were also performed to evaluate the stability-indicating properties and specificity of the method. Medroxyprogesterone was eluted at 5.9 minutes. The linearity of the method was confirmed in the range of 0.0576 to 0.1134 mg/mL (R2 > 0.999). The limit of quantification was shown to be 3.9 µg/mL. Precision and accuracy ranges were found to be %RSD <0.2 and 98% to 102%, respectively. Medroxyprogesterone capacity factor value of 2.1, tailing factor value of 1.03, and resolution value of 3.9 were obtained in accordance with ICH guidelines. Based on the obtained results, a rapid, precise, accurate, sensitive, and cost-effective analysis procedure was proposed for quantitative determination of medroxyprogesterone in vaginal sponges. This analytical method is the only available method to analyse medroxyprogesterone in veterinary intravaginal dosage form.

OBJECTIVE: The purpose of this study was to compare the effects of ormeloxifene with medroxyprogesterone acetate in patients with abnormal uterine bleeding.
METHODS: 440 Patients were divided into two groups. In group A, ormeloxifene was given at the dosage of 60 mg twice a week for 3 months followed by 60 mg once a week for 1 month. In group B, medroxyprogesterone acetate was given at the dosage of 10 mg twice a day from day 5 to day 25 of the menstrual cycle. At follow-ups, patients were assessed for PBAC score, endometrial thickness by USG, hemoglobin level, and the side effects of drug therapy.
RESULTS: There were 240 patients in group A and 200 in group B. Reduction in median PBAC score was 79.4 % in group A and 75 % in group B after 4 months of treatment. The mean duration of bleeding reduced to 4.8 from 9 in group A and 5 from 8.7 in group B. Mean hemoglobin was increased from 8.6 to 9.8 g % in group A and from 8.7 to 9.9 g % in group B; endometrial thickness was reduced from 7.7 mm to 6.8 mm in group A and from 7.4 mm to 6.9 mm in group B.
CONCLUSIONS: We conclude from this study that ormeloxifene should be considered the first choice in the management of AUB, especially in the perimenopausal age group where amenorrhea is acceptable.