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Archives of Gynecology and Obstetrics Apr 2024Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for... (Review)
Review
PURPOSE
Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer.
METHODS
Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review.
RESULTS
All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk.
CONCLUSION
There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.
Topics: Female; Humans; Medroxyprogesterone Acetate; Delayed-Action Preparations; Breast Neoplasms; Contraceptive Agents, Female; Progestins
PubMed: 37966517
DOI: 10.1007/s00404-023-07265-5 -
PloS One 2023South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age.
METHODS
We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18-33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing.
RESULTS
There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups- 18-21 years (46%), 22-25 years (42%) and 26-33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18-21 years) more likely to acquire CT (75.9/100 wy) compared to 26-33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26-33 year old group (82.7/100 wy) compared to the 18-21 year olds (8.4/100 wy; p = 0.01).
CONCLUSIONS
Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.
Topics: Male; Humans; Female; Adolescent; Young Adult; Adult; South Africa; Contraceptive Agents; Prevalence; Incidence; Sexually Transmitted Diseases; Chlamydia trachomatis; Trichomonas vaginalis; Neisseria gonorrhoeae; HIV Infections; Chlamydia Infections
PubMed: 37948399
DOI: 10.1371/journal.pone.0294285 -
Scientific Reports Nov 2023There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women...
There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.
Topics: Female; Humans; Pregnancy; Black People; Contraceptives, Oral; Leiomyoma; Reproduction; Risk Factors
PubMed: 37919335
DOI: 10.1038/s41598-023-44703-5 -
Frontiers in Global Women's Health 2023Expanding access to contraceptive services by making them available in pharmacies and drug shops is a family planning high-impact practice. In 2018, Kenya's Ministry of...
Expanding access to contraceptive services by making them available in pharmacies and drug shops is a family planning high-impact practice. In 2018, Kenya's Ministry of Health amended its family planning guidelines to allow pharmacists and pharmaceutical technologists throughout the country to provide subcutaneous and intramuscular depot medroxyprogesterone acetate. Amending the policy did not necessarily mean that the policy would be implemented. The Advance Family Planning project launched an advocacy campaign to engage key stakeholders to work with the Ministry of Health to implement the policy. Consequently, a family planning training package for pharmacists and pharmaceutical technologists was developed and rolled out. The advocacy process also led to strengthening family planning reporting by the trained pharmacists and pharmaceutical technologists. To further enhance sustainability by ensuring a continuous pool of pharmacy professionals equipped with skills to provide family planning services, Advance Family Planning and its partners advocated with universities and the Pharmacy and Poisons Board to revise the pre-service training curriculum to include family planning as a competence area for pharmacists and pharmaceutical technologists. A key lesson learned is that policy formulation does not necessarily translate to policy implementation. Advocacy is often needed to move policy to practice, especially where resources are required. Policy implementation also requires incremental achievement of milestones and the need for advocacy for each step in the process. Implementation of the policy provision that allows pharmacists and pharmaceutical technologists to provide injectable contraceptives has implications beyond family planning programs. It provides a point of reference for allowing pharmacists to offer other primary health care services, such as immunization, injectable HIV prophylaxis, and other interventions that might not be provided for in policy.
PubMed: 37901119
DOI: 10.3389/fgwh.2023.1218220 -
Reproductive Biology and Endocrinology... Oct 2023Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence...
METTL3-regulated m6A modification impairs the decidualization of endometrial stromal cells by regulating YTHDF2-mediated degradation of FOXO1 mRNA in endometriosis-related infertility.
BACKGROUND
Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation.
METHODS
We examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A.
RESULTS
The expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein.
CONCLUSIONS
METTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.
Topics: Animals; Female; Humans; Mice; Endometriosis; Epigenesis, Genetic; Forkhead Box Protein O1; Methyltransferases; RNA, Messenger; RNA-Binding Proteins; Stromal Cells; Transcription Factors; Infertility, Female
PubMed: 37891533
DOI: 10.1186/s12958-023-01151-0 -
Frontiers in Molecular Biosciences 2023The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has posed a significant challenge to individuals' health. Increasing evidence shows that patients with...
The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has posed a significant challenge to individuals' health. Increasing evidence shows that patients with metabolic unhealthy obesity (MUO) and COVID-19 have severer complications and higher mortality rate. However, the molecular mechanisms underlying the association between MUO and COVID-19 are poorly understood. We sought to reveal the relationship between MUO and COVID-19 using bioinformatics and systems biology analysis approaches. Here, two datasets (GSE196822 and GSE152991) were employed to extract differentially expressed genes (DEGs) to identify common hub genes, shared pathways, transcriptional regulatory networks, gene-disease relationship and candidate drugs. Based on the identified 65 common DEGs, the complement-related pathways and neutrophil degranulation-related functions are found to be mainly affected. The hub genes, which included SPI1, CD163, C1QB, SIGLEC1, C1QA, ITGAM, CD14, FCGR1A, VSIG4 and C1QC, were identified. From the interaction network analysis, 65 transcription factors (TFs) were found to be the regulatory signals. Some infections, inflammation and liver diseases were found to be most coordinated with the hub genes. Importantly, Paricalcitol, 3,3',4,4',5-Pentachlorobiphenyl, PD 98059, Medroxyprogesterone acetate, Dexamethasone and Tretinoin HL60 UP have shown possibility as therapeutic agents against COVID-19 and MUO. This study provides new clues and references to treat both COVID-19 and MUO.
PubMed: 37877121
DOI: 10.3389/fmolb.2023.1274463 -
Contraception: X 2023This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing...
OBJECTIVES
This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient.
STUDY DESIGN
We conducted a randomized, crossover, single-center study. Twenty-seven healthy women aged 25 to 47 years at low risk of pregnancy received a subcutaneous injection of each of the four study drugs (120 mg/0.3 mL of TV-46046, 60 mg/0.3 mL of diluted TV-46046, 0.3 mL of TV-46046 placebo, and 104 mg/0.65 mL of Depo-subQ 104) in different quadrants of the abdomen. We assessed local tolerability by occurrence of injection site reactions (ISRs), as well as injection site pain and overall safety for at least 9 months postinjections.
RESULTS
Of a total of 108 study injections, three injections were partial due to needle blockage. We observed a total of 30 ISRs following 105 full-dose injections, including hypopigmentation ( = 24), bruising ( = 4), and atrophy/dimple ( = 2). Eleven cases of hypopigmentation occurred following 25 full-dose injections of undiluted TV-46046 (44.0%), six following 27 full-dose injections of diluted TV-46046 (22.2%), and seven following 26 full-dose injections of Depo-subQ 104 (26.9%). Hypopigmentations occurred on average 8 months postinjection. Injection pain was minimal and dissipated quickly after all four injections.
CONCLUSIONS
Subcutaneous administration of MPA in a suspension formulation is associated with the delayed onset of hypopigmentation at the site of injection. Although not statistically significant, the rate of ISRs was over 60% higher for undiluted TV-46046 compared to Depo-subQ 104. This difference bears careful monitoring in future studies of TV-46046.
IMPLICATIONS
From a safety standpoint, investigational drug TV-46046 is appropriate for further clinical testing as a 6-month contraceptive injectable. The previously underreported hypopigmentation associated with subcutaneous administration of MPA warrants further investigation and acceptability assessment among users of existing Depo-subQ 104 as well as careful monitoring of local tolerability of TV-46046 in future clinical trials.
TRIAL REGISTRATION
Registered at clinicaltrials.gov no: NCT02817464.
PubMed: 37823034
DOI: 10.1016/j.conx.2023.100100 -
Genomics & Informatics Sep 2023Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The...
Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DE miRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co-expression network. Next, four modules were selected based on the Zsummary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.
PubMed: 37813634
DOI: 10.5808/gi.23039 -
Journal of Clinical Medicine Sep 2023To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible...
Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study.
RESEARCH QUESTION
To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria.
DESIGN
Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR.
RESULTS
The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, = 1.000).
CONCLUSION(S)
The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients.
PubMed: 37762716
DOI: 10.3390/jcm12185775 -
Open Medicine (Warsaw, Poland) 2023We aimed to evaluate the effects of postpartum progesterone on obstetric anal sphincter injury (OASI) healing in female rats using an experimental OASI model....
We aimed to evaluate the effects of postpartum progesterone on obstetric anal sphincter injury (OASI) healing in female rats using an experimental OASI model. Twenty-eight female rats were divided into four groups after birth: sham-30, sham-90, progesterone (P4)-30, and P4-90. Moreover, OASI model was established in all groups. Subsequently, except for the sham groups, medroxyprogesterone acetate (0.15 mg) was intramuscularly injected into the P4 groups. After 30 and 90 days, the rats were euthanized under general anesthesia after recording the data. The anal sphincter region was collected for histopathological examination. Progesterone and thiol/disulfide homeostasis studies were performed on blood samples. No significant differences were observed between the groups regarding the external anal sphincter (EAS), internal anal sphincter (IAS), or connective tissue thickness ( = 0.714, = 0.135, and = 0.314, respectively). No statistically significant differences in the total thiol, native thiol, disulfide, and progesterone levels were found between the groups ( = 0.917, = 0.503, = 0.361, and = 0.294, respectively). The endometrial thickness was lower in the P4 groups than in the sham groups ( = 0.031). Postpartum progesterone administration did not affect IAS and EAS or connective tissue thickness or disrupt the thiol-disulfide balance. However, this administration led to endometrial thinning.
PubMed: 37693836
DOI: 10.1515/med-2023-0786