The Association between Medroxyprogesterone Acetate Exposure and Meningioma.

BACKGROUND/OBJECTIVES: Medroxyprogesterone acetate (MPA) is a synthetic progesterone that is most commonly used as a contraceptive. MPA acts by binding to the progesterone receptor of the hypothalamus, and this receptor has been found to be important in the pathophysiology of meningiomas. Recent research has reported an increased association between the use of MPA and intracranial meningioma, though the literature is mostly limited by low numbers of meningioma cases and low exposure to MPA. The objective of the current study is to build upon the previously published literature utilizing a large database from the United States. METHODS: Utilizing a large commercial insurance database, the current matched case-control study identified meningioma cases using ICD-10 codes from hospital data and MPA exposure, as established from pharmaceutical claims data. Controls were matched 10:1 to cases based on age, year of enrollment, and duration of enrollment. A conditional logistic regression estimated odds ratios (ORs) for the association between MPA exposure and the odds of developing a meningioma. RESULTS: Among 117,503 meningioma cases and 1,072,907 matched controls, oral MPA exposure was not associated with odds of meningioma; however, injection MPA exposure was associated with a 53% increased odds of being a case (OR 1.53, 95% CI 1.40-1.67). This association was specific to cerebral meningiomas (OR 1.68, 95% CI 1.50-1.87), an association that became stronger with a longer duration of use of injection MPA. CONCLUSIONS: The current results are consistent with the prior literature, which reports an association between injection exposures to MPA and a stronger association with increasing use of MPA. Women should be cautioned about the prolonged use of MPA, and future research should examine whether the extended use of MPA is associated with the meningioma grade.

Potential effect of immediate postpartum use of injectable contraception on lactogenesis.

OBJECTIVES: We evaluated the effect of immediate postpartum use of depot medroxyprogesterone acetate (DMPA) on the timing of lactogenesis stage II (LS-II). STUDY DESIGN: The initial design randomly assigned adults who delivered a full-term infant in 2019-2021 to receive within 48 hours of delivery: 1) DMPA, 2) placebo injection, or 3) no injection. Due to low enrollment, we changed in 2021-2023 to a non-randomized design using matching at recruitment for obesity and delivery method and propensity score weighting for analysis. We combined data from both designs to compare immediate postpartum DMPA use (N=55) versus control (placebo or no injection) group (N=95). We defined noninferiority a priori as being met if the upper bound of a two-sided 95% confidence interval (CI) for mean difference in time to LS-II between groups was <6 hours. RESULTS: The unweighted mean time to LS-II was 57.8 hours in the DMPA group (SD, 29.4) and 64.1 hours in the control group (SD, 36.1). Using propensity score weighting to make the groups comparable with respect to age, race, delivery method, and previous live births, the mean time to LS-II was 5.5 hours shorter (95% CI, -16.4, 5.5) for women in the DMPA relative to control group. CONCLUSIONS: We found no evidence that DMPA use inhibits the onset of LS-II. Findings support immediate postpartum DMPA initiation among those intending to engage in human milk feeding. IMPLICATIONS: A controlled trial (N=150) did not detect any difference in time to lactogenesis stage II ("milk let-down") between injectable contraception use within the first 48 hours postpartum and those without this exposure.

Clinical outcomes of three follitropin alfa preparations for ovarian stimulation using an oral micronized progesterone-primed protocol in an oocyte donation program.

Introduction: This large multicenter study aimed to evaluate clinical outcomes using three follitropin alfa preparations within a progestin-primed ovarian stimulation (PPOS) protocol, while identifying contributing factors to cycle success. Methods: A retrospective, anonymized cohort analysis was conducted on donor-recipient cycles from 12 clinics during 2019 to 2021. 7389 oocyte donors underwent ovarian stimulation (OS) with three follitropin alfa preparations (Ovaleap® [n=3231], Bemfola® [n=3542], Gonal-F® [n=616]) were included. Stimulation began on cycle days 2 or 3 with daily administration of 150-225 IU follitropin alfa. 10 mg medroxyprogesterone acetate (MPA) was administered daily until GnRH agonist trigger using a single dose of 0.2mg GnRH agonist for final follicular maturation. Statistical analysis included ANOVA, Chi-squared, and logistic regression. Results: Whilst there were some differences in patient and stimulation characteristics, including donor age and number of retrieved oocytes, clinical variables did not significantly differ among the three study groups. Linear regression revealed donor age [0.986 (0.974-0.999)] and number of mature oocytes [1.027 (1.007-1.047)] significantly impacted ongoing pregnancy rates, while the type of follitropin alfa [1.048 (0.956-1.149)] used did not. No significant differences were observed in the cumulative live birth rate (CLBR) among oocytes obtained from stimulation with Bemfola (64.9%), Gonal-F (64.1%) and Ovaleap (66.1%), p= 0.385. Discussion: This study demonstrated comparable clinical outcomes and CLBR between biosimilars and the reference product of follitropin alfa within PPOS protocols, hence they are interchangeable in a real-world patient setting.

Mammary carcinoma in a male cat following long-term medroxyprogesterone acetate treatment: case report and review of the literature.

In male cats, as in men, mammary carcinomas are rarely reported. However, like in females, hormonal therapy is a significant risk factor. This study reports the case of an 11-year-old male cat with multiple mammary tumours and a history of long-term medroxyprogesterone acetate therapy for the suppression of sexual behaviour, along with a brief review of the literature. Complete surgical removal of the right mammary chain and the ipsilateral inguinal lymph nodes was performed, and all tissues were submitted for histology. Histological examination revealed the presence of a tumour in the third and fourth mammary glands, consisting of neoplastic cells arranged in various structures, including tubulopapillary and tubular structures, sometimes cystically dilated, and solid areas. The inguinal lymph nodes were also involved. The morphology was consistent with a diagnosis of mammary carcinoma, tubulopapillary type, with nodal metastases. Immunohistochemistry revealed that tumour cells were positive for cytokeratin (clones AE1/AE3), while stromal cells were positive for vimentin (clone V9). The proliferation marker Ki-67, evaluated on both the primary tumour and the nodal metastases, was strongly expressed in the nuclei of neoplastic cells, with a Ki-67 proliferation index of 8.9% and 20% for the primary tumour and the metastases, respectively. This case highlights the importance of considering the possibility of malignant mammary tumours not only in female but also in male cats with a history of long-term hormonal treatment for suppression of sexual behaviour.

Injection Depot Medroxyprogesterone Acetate as an Early Postpartum Contraceptive Measure: Evaluation of Its Acceptability, Efficacy, and Impact on Lactation.

Introduction Through its National Family Planning Programme, India has been relentlessly working to decrease society's unmet contraception needs. The postpartum period is of paramount importance for addressing these contraceptive needs owing to alterations in fertility and coital behavior associated with childbirth. Depot medroxyprogesterone acetate (DMPA), a long-acting reversible contraceptive, is one of the safe options available in the early postpartum period. In this study, we aimed to evaluate its efficacy and acceptability among postpartum women delivering in Guru Gobind Singh Medical College and Hospital. Methodology We recruited 206 early postpartum women for the study. After thorough counseling and ensuring establishment of lactation, we administered DMPA 150mg by injection intramuscularly and repeated it at intervals of three months in willing patients. We then evaluated them for their symptoms, side effects, and lactation status using a predesigned proforma either during their follow-up visits or telephonically. Results We found DMPA to be 100% efficacious as an early postpartum contraceptive measure. The main reasons for acceptance were its ease of use, long-term effects of a single dose, and noninterference with lactation. However, the continuation rate for the second dose was only 18% in our study, highlighting the need for better counseling and improving awareness among our patients. Ninety-nine percent of our patients were satisfied with their lactation. Conclusion We found injectable DMPA used as a contraceptive in the immediate postpartum period to be a safe and effective alternate method with no deleterious effect on lactation and an acceptable side effect profile. However, more awareness programs are necessary to encourage women, especially those in low-resource areas, to continue using DMPA.

Preventing recurrence of endometriosis-related pain by means of long-acting progestogen therapy: the PRE-EMPT RCT.

Background: Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Recurrence of symptoms following an operation is common. Although hormonal treatment can reduce this risk, there is uncertainty about the best option. Objectives: To evaluate the clinical and cost-effectiveness of long-acting progestogen therapy compared with the combined oral contraceptive pill in preventing recurrence of endometriosis-related pain and quality of life. Design: A multicentre, open, randomised trial with parallel economic evaluation. The final design was informed by a pilot study, qualitative exploration of women's lived experience of endometriosis and a pretrial economic model. Setting: Thirty-four United Kingdom hospitals. Participants: Women of reproductive age undergoing conservative surgery for endometriosis. Interventions: Long-acting progestogen reversible contraceptive (either 150 mg depot medroxyprogesterone acetate or 52 mg levonorgestrel-releasing intrauterine system) or combined oral contraceptive pill (30 µg ethinylestradiol, 150 µg levonorgestrel). Main outcome measures: The primary outcome was the pain domain of the Endometriosis Health Profile-30 questionnaire at 36 months post randomisation. The economic evaluation estimated the cost per quality-adjusted life-years gained. Results: Four hundred and five women were randomised to receive either long-acting reversible contraceptive (N = 205) or combined oral contraceptive pill (N = 200). Pain scores improved in both groups (24 and 23 points on average) compared with preoperative values but there was no difference between the two (adjusted mean difference: -0.8, 95% confidence interval -5.7 to 4.2; p = 0.76). The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the combined oral contraceptive group (73 vs. 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). The mean adjusted quality-adjusted life-year difference between two arms was 0.043 (95% confidence interval -0.069 to 0.152) in favour of the combined oral contraceptive pill, although this cost an additional £533 (95% confidence interval 52 to 983) per woman. Limitations: Limitations include the absence of a no-treatment group and the fact that many women changed treatments over the 3 years of follow-up. Use of telephone follow-up to collect primary outcome data in those who failed to return questionnaires resulted in missing data for secondary outcomes. The COVID pandemic may have affected rates of further surgical treatment. Conclusions: At 36 months, women allocated to either intervention had comparable levels of pain, with both groups showing around a 40% improvement from presurgical levels. Although the combined oral contraceptive was cost-effective at a threshold of £20,000 per quality-adjusted life-year, the difference between the two was marginal and lower rates of repeat surgery might make long-acting reversible contraceptives preferable to some women. Future work: Future research needs to focus on evaluating newer hormonal preparations, a more holistic approach to symptom suppression and identification of biomarkers to diagnose endometriosis and its recurrence. Trial registration: This trial is registered as ISRCTN97865475. https://doi.org/10.1186/ISRCTN97865475. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/114/01) and is published in full in Health Technology Assessment; Vol. 28, No. 55. See the NIHR Funding and Awards website for further award information. The NIHR recognises that people have diverse gender identities, and in this report, the word 'woman' is used to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary.

Endometriosis is a condition where cells similar to ones that line the womb are found elsewhere in the body. Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Unfortunately, symptoms often return and some women will need repeat operations. Hormonal contraceptives can prevent the return of endometriosis-related pain: either long-acting reversible contraceptives (injections or a coil, fitted inside the womb) or the combined oral contraceptive pill (often called 'the pill'). We do not know which is the best option. The aim of this trial was to find out which of these two hormone treatments was more effective in terms of symptom relief, avoidance of further surgery and costs. Four hundred and five women with endometriosis, who were not intending to get pregnant, participated in a clinical trial. Half of the participants took long-acting reversible contraceptives, and the other half took the pill for 3 years following endometriosis surgery. The choice of treatment was made at random by a computer to ensure a fair comparison, although those allocated to the long-acting contraceptive could choose between injections or the coil. Participants completed questionnaires about their symptoms and life quality at intervals up to 3 years. Both treatments were equally good at reducing pain but more women using the pill had repeat operations. The pill was a little more costly overall but associated with a slightly higher quality of life. Both treatments are equally effective in reducing pain up to 3 years after surgery for endometriosis. The differences in costs are small and the choice of treatment should be based on personal preference.

Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer.

AIMS: To evaluate the safety and effectiveness of high-dose oral medroxyprogesterone acetate (MPA) therapy as a fertility-sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. METHODS: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post-MPA therapy pregnancies were examined. RESULTS: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post-CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. CONCLUSIONS: High-dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.

Novel dissolution methods for drug release testing of Long-Acting injectables.

Long-acting parenteral drug products are a popular choice for therapeutic areas requiring long term treatment. These products range from dispersed systems such as drug suspensions and polymeric microspheres to in situ forming polymeric implants. The lack of reliable drug release testing methods for these drug products not only impedes the development of new drug products but also affects generic drug development. Current release methods suffer from a range of problems such as high variability, poor reproducibility, poor discriminatory ability, lack of depot-like structure formation (that could mimic the in vivo situation). Moreover, shorter duration (less than a week) of release renders them unsuitable for in vitro-in vivo correlations (IVIVCs). To overcome these issues, novel adapters were developed for both USP-type-II & IV apparatus. These adapters were validated and assessed using the long-acting injectable (LAI) suspension drug product Depo Provera 150® as well as its Q1/Q2 equivalents. For USP-type-IV apparatus, two open adapter designs (conical and ellipsoidal shaped cavity with volume capacities of 50 µl and 1 ml, respectively) were developed. A closed conical adapter design with a volume capacity of 0.05 ml was developed for USP apparatus type-II. All three novel adapter designs effectively retained the suspensions, achieved release durations of 3-6 weeks with good reproducibility, minimal variability (RSD≤5%) and had good discriminatory ability. Based on this, the adapter-based dissolution methods were deemed suitable for IVIVC development of long-acting injectables. A successful Level A IVIVC was developed for Depo SubQ Provera 104® and its Q1Q2 equivalents using USP apparatus type IV with a conical adapter design. The closed adapter design for apparatus type-II was also investigated for suitability with risperidone in situ forming implants. The adapter was able to securely retain and maintain the shape of the in situ forming implants and resulted in release profiles of up to one month with good discriminatory ability and low standard error (RSD≤5%). These novel adapters hold promise of wide use for in vitro release testing of different long-acting parenteral drug products.

A case report and literature review: A 19-year-old with endometrial carcinoma treated with medroxyprogesterone acetate. Importance of the medical interview and endometrial examination.

A 19-year-old woman had stage IA endometrial carcinoma treated with medroxyprogesterone acetate and experienced a recurrence. This patient's experience illustrates the importance of a thorough history and endometrial assessment in younger patients.

Efficacy of medication abortion with concurrent initiation of progestin contraceptives: A retrospective cohort study.

OBJECTIVES: To evaluate medication abortion (MAB) outcomes for participants receiving intramuscular depot medroxyprogesterone acetate (DMPA) injections or subdermal etonogestrel implants concurrently with mifepristone compared to those who did not in a real-world setting. STUDY DESIGN: This retrospective cohort study included MAB patients from one Planned Parenthood health center in St. Paul, MN, between 2017 and 2019. We abstracted electronic health records and compared sociodemographic variables, clinical information, and treatment failure rates (primary outcome) between study groups with logistic regression (generating odds ratios [OR] and 95% confidence intervals [CI]). RESULTS: Among 7296 MAB participants, 224 (3.1%) received DMPA injections and 309 (4.2%) received etonogestrel implants concurrently with mifepristone; 141 (62.9%) and 200 (64.7%) completed follow-up respectively. From a random sample of 1000, 990 comparison participants met inclusion criteria; 704 (71.1%) completed follow-up. Fourteen (9.9%) DMPA participants (aOR 4.26, 95% CI 1.87-9.68, p < 0.001) and 6 (3.0%) etonogestrel implant participants (aOR 1.38, 95% CI 0.48-3.55, p = 0.522) required additional treatment to empty the uterus and/or had an ongoing pregnancy, each contrasted with 15 (2.1%) comparison patients (models adjusted for gestational duration, patient age, parity, and race). CONCLUSION: Although our study is limited by high rates of loss to follow-up, our analysis suggests that concurrent administration of DMPA with mifepristone may decrease MAB efficacy, while etonogestrel implant placement does not appear to alter MAB outcomes. These findings are overall consistent with prior literature and inform post-MAB contraception counseling. IMPLICATIONS: This retrospective cohort study reinforces prior randomized controlled trial findings that concurrent depot medroxyprogesterone acetate injection with mifepristone administration may decrease medication abortion efficacy. Conversely, concurrent etonogestrel contraceptive implant placement with mifepristone administration does not appear to decrease medication abortion efficacy. These findings inform post-abortion contraception counseling.

Progestin-primed ovarian stimulation with letrozole using different doses of medroxyprogesterone acetate per day: a retrospective cohort study.

Background: In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. Method: This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. Results: In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Conclusion: Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.

In vitro fertilization results of GNRH antagonists and medroxyprogesterone acetate used to prevent premature LH surge during ovarian hyperstimulation.

The aim of this study was to evaluate the effects of medroxyprogesterone acetate (MPA) treatment in comparison to those of gonadotropin releasing hormone (GnRH) antagonists for the prevention of premature luteinizing hormone surges during controlled ovarian hyperstimulation (OS) and the impact of these effects on developing embryos and pregnancy outcomes. Data from 757 cycles of GnRH antagonist treatment and 756 cycles of MPA treatment were evaluated at the Akdeniz University Faculty of Medicine Assisted Reproductive Treatment Center between October 2018 and April 2022. Patient records were obtained from the electronic database of the centre and analysed. In our centre, GnRH antagonist protocols were used between 2018 and 2020, and MPA protocols were used between 2020 and 2022. We chose our study population by year. Our study is a comparative retrospective study. All methods in this study were performed in accordance with the relevant guidelines and regulations. Patients using MPA were significantly older (33.9 ± 5.6 vs. 32.6 ± 5.6, p < 0.001) and had a lower number of antral follicles (AFC) (10.7 ± 8.6 vs. 11.9 ± 10.8, p = 0.007) than those using GnRH antagonists. Both MPA (2.9%) and GnRH antagonists (2.2%) had similar effectiveness in preventing premature ovulation (p = 0.415). There was no significant difference between the two groups in terms of the number of total developed embryos (1.3 ± 1.3 vs. 1.2 ± 1.2, p = 0.765). There was no significant difference in the clinical pregnancy rates with the first ET (%35.4 vs. %30.1, p = 0.074), per total number of transfers (35.3% vs. 30.1%, p = 0.077). MPA was found to be effective at preventing premature ovulation during OS treatment, and the incidence of developing embryo and pregnancy outcomes in patients using MPA were similar to those in patients using GnRH antagonists. Therefore, the use of MPA instead of GnRH antagonists during OS may be a viable alternative for patients not scheduled for fresh ET.

Counseling Women About Sexual Health Effects of Contraceptives.

Background: Choosing a contraceptive method is a pivotal decision for patients, whereas health care professionals (HCPs) face challenges in providing suitable recommendations. Adverse sexual effects often lead to dissatisfaction and discontinuation of contraceptives, underscoring the importance of thorough counseling and shared decision making between HCPs and patients. Objective: This article aims to investigate the relationship between contraceptive methods and female sexual function through a comprehensive review of available literature, emphasizing the importance of considering sexual health in contraceptive prescription and management. Methods: A systematic analysis of existing literature, incorporating studies utilizing validated sexual health questionnaires, was conducted to elucidate the intricate interplay between contraceptives and female sexual function. Results: The review encompasses various contraceptive methods, including combined hormonal contraceptives, progestin-only pills, depot medroxyprogesterone acetate, subdermal contraceptive implants, hormonal intrauterine devices, permanent sterilization, and barrier methods. Insights gleaned from the analysis shed light on the impact of these methods on female sexual health. Conclusion: Comprehensive understanding of the effects of contraceptives on female sexual function is crucial for both HCPs and patients. By integrating sexual health considerations into contraceptive surveillance, compliance can be improved, contraceptive efficacy optimized, and the risk of unwanted pregnancies minimized. This review underscores the significance of tailored counseling and shared decision making in contraceptive management, particularly for cisgender women.

Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

Background: For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. Methods: This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. Results: For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). Conclusions: For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

Acceptance, Adherence, and Side Effects of Depot Medroxyprogesterone Acetate: A Prospective Observational Study.

Introduction In India, one of the world's most populous and swiftly growing countries, it is crucial to prioritize the utilization of safe and effective contraception, as contraceptive strategies play a pivotal role in bolstering community health. It is widely acknowledged that ensuring appropriate timing and spacing of pregnancies is crucial for the well-being of reproductive, maternal, neonatal, child, and adolescent health. Adoption of reversible or spacing contraceptive methods can significantly enhance women's health outcomes by reducing the occurrence of undesired, closely timed, and mistimed pregnancies. Consequently, in response to the pressing need for dependable contraception in India, this study seeks to assess the acceptance, adherence, and side effects of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) among its users. Methods This prospective observational study was done at the State Government Taluk Hospital in the Cuddalore District of Tamil Nadu from July 2022 to October 2022. A total of 40 women of reproductive age who opted for DMPA as their contraceptive method and met the inclusion criteria were recruited through a purposive sampling method. A structured questionnaire was used to collect the data. Results The majority of the participants were women aged 21-25 years (n=14; 35%). The participants were predominantly Hindu (n=39; 97.5%), and 35 (87.5%) had completed higher secondary education. All participants (n=40; 100%) resided in rural areas and the majority were homemakers. A significant proportion of the participants had two children (n=21; 52.5%), and all of them received information on DMPA primarily from health personnel. At the initial point of data collection, three-fourths of them took the first dose (n=13; 32.5%) and only a few took more than three doses (n=3; 7.5%). In the third month, the results showed a drop in DMPA use, which indicates a lower adherence particularly linked to side effects like irregular bleeding (n=15; 37.5%) and amenorrhea (n=9; 22.5%). Furthermore, 35 (87.5%) of the women chose DMPA for birth spacing due to its efficacy and convenience, with few initiating it during postpartum (n=4; 10%) and post-abortal (n=1; 2.5%) periods. The reasons for continuing DMPA use included efficacy (n=20; 50%), discreet usage (n=15; 37.5%), and curiosity (n=13; 32.5%). Half of the participants reported no side effects. The study identified associations between DMPA users and the number of living children and occupational status inferring that DMPA contraception is used for spacing births. Conclusion The results of this study imply that the use and adherence to injectable contraceptive DMPA need to be strengthened among rural women. Thus, the study suggests incorporating information, education, and communication strategies, to enhance awareness among rural women about injectable contraceptives.

Clomiphene citrate as a new modality in management of vaginal bleeding with depomedroxyprogesterone acetate (DMPA): A randomized controlled trial.

BACKGROUND: Depo-medroxyprogesterone acetate (DMPA) functions as a contraceptive method by inhibiting the secretion of gonadotropins, which prevents follicular maturation and ovulation, as well as thinning of the endometrium leading to unscheduled vaginal bleeding and subsequent discontinuation of DMPA. Our study aimed to evaluate the efficacy and safety of clomiphene citrate (CC) in stopping bleeding among DMPA users. MATERIALS AND METHODS: We randomly assigned 200 DMPA users using a computer-generated random numbers table in a 1:1 ratio to one of two groups; the study group, which received CC at a dose of 50 mg twice daily for five days (n = 100), and the control group, which received a placebo for five days (n = 100). Our primary outcome measure was the onset and duration of bleeding cessation. Secondary outcomes included endometrial thickness, recurrence of vaginal bleeding, and any reported side effects associated with CC use. RESULTS: Clomiphene citrate significantly resulted in early cessation of vaginal bleeding in 83 % of the patients, which continued for three months of follow-up. In addition, the recurrence of vaginal bleeding was significantly reduced in the CC group compared to the control group (11 % vs. 67 %; p < 0.001). Endometrial thickness was significantly greater in the CC group than in the control group (p < 0.001). Breast tenderness was more frequently reported in the study group, with no difference in dyspareunia between the two groups. CONCLUSIONS: Clomiphene citrate is effective in controlling bleeding among DMPA users. Further studies are encouraged to confirm our findings.

Development of Mechanistic In Vitro-In Vivo Extrapolation to Support Bioequivalence Assessment of Long-Acting Injectables.

Long-acting injectable (LAI) formulations provide sustained drug release over an extended period ranging from weeks to several months to improve efficacy, safety, and compliance. Nevertheless, many challenges arise in the development and regulatory assessment of LAI drug products due to a limited understanding of the tissue response to injected particles (e.g., inflammation) impacting in vivo performance. Mechanism-based in silico methods may support the understanding of LAI-physiology interactions. The objectives of this study were as follows: (1) to use a mechanistic modeling approach to delineate the in vivo performance of DepoSubQ Provera® and formulation variants in preclinical species; (2) to predict human exposure based on the knowledge gained from the animal model. The PBPK model evaluated different elements involved in LAI administration and showed that (1) the effective in vivo particle size is potentially larger than the measured in vitro particle size, which could be due to particle aggregation at the injection site, and (2) local inflammation is a key process at the injection site that results in a transient increase in depot volume. This work highlights how a mechanistic modeling approach can identify critical physiological events and product attributes that may affect the in vivo performance of LAIs.

TET3-mediated DNA demethylation modification activates SHP2 expression to promote endometrial cancer progression through the EGFR/ERK pathway.

OBJECTIVE: Src homology phosphotyrosin phosphatase 2 (SHP2) has been implicated in the progression of several cancer types. However, its function in endometrial cancer (EC) remains unclear. Here, we report that the ten-eleven translocation 3 (TET3)-mediated DNA demethylation modification is responsible for the oncogenic role of SHP2 in EC and explore the detailed mechanism. METHODS: The transcriptomic differences between EC tissues and control tissues were analyzed using bioinformatics tools, followed by protein-protein interaction network establishment. EC cells were treated with shRNA targeting SHP2 alone or in combination with isoprocurcumenol, an epidermal growth factor receptor (EGFR) signaling activator. The cell biological behavior was examined using cell counting kit-8, colony formation, flow cytometry, scratch assay, and transwell assays, and the median inhibition concentration values to medroxyprogesterone acetate/gefitinib were calculated. The binding of TET3 to the SHP2 promoter was verified. EC cells with TET3 knockdown and combined with SHP2 overexpression were selected to construct tumor xenografts in mice. RESULTS: TET3 and SHP2 were overexpressed in EC cells. TET3 bound to the SHP2 promoter, thereby increasing the DNA hydroxymethylation modification and activating SHP2 to induce the EGFR/extracellular signal-regulated kinase (ERK) pathway. Knockdown of TET3 or SHP2 inhibited EC cell malignant aggressiveness and impaired the EGFR/ERK pathway. Silencing of TET3 inhibited the tumorigenic capacity of EC cells, and ectopic expression of SHP2 or isoprocurcumenol reversed the inhibitory effect of TET3 knockdown on the biological activity of EC cells. CONCLUSION: TET3 promoted the DNA demethylation modification in the SHP2 promoter and activated SHP2, thus activating the EGFR/ERK pathway and leading to EC progression.

Depot medroxyprogesterone acetate concentrations in patients with and without the use of antiseizure medications.

OBJECTIVES: To measure plasma concentrations of medroxyprogesterone acetate (MPA) in users with epilepsy treated with antiseizure medications and compare these to MPA concentrations in those without epilepsy. STUDY DESIGN: For this multisite cross-sectional study, we obtained a single blood sample from those with epilepsy treated with various antiseizure medications (n = 18) within the week before their next depot medroxyprogesterone injection. Among the participants without epilepsy (n = 20), 10 similarly were scheduled within the week prior to the next injection, and 10 were scheduled at earlier intervals to attempt to balance the time intervals between groups. MPA concentrations were determined by a validated assay. RESULTS: MPA concentrations were similar among those with epilepsy and controls and between groups with and without the use of enzyme-inducing medications. The lowest MPA concentrations, under 0.07 ng/mL, were observed among two of eight using enzyme-inducing antiseizure medications, one of 10 using noninducing medications, and one of 19 controls had concentrations below 0.2 ng/mL. CONCLUSIONS: In this exploratory study, lower MPA concentrations in some participants using enzyme-inducing antiseizure medications suggest a potential interaction that could reduce depot medroxyprogesterone efficacy.