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Viruses Nov 2021The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the...
The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the changes occurring in the female genital mucosa and blood. However, one of the main sites of HIV-1 pathogenesis is lymphoid organs. To investigate the immunoregulatory effect of medroxyprogesterone acetate (MPA) at this site, human tonsillar tissue explants were infected ex vivo with either a CCR5 (BaL) or CXCR4 (LAI) HIV-1 variant and the release of p24 and cytokines was measured in culture supernatant. The response to MPA was compared with that elicited by treatment with progesterone (P4) and dexamethasone (DEX), which selectively binds the glucocorticoid receptor, in donor-matched explant cultures. MPA treatment reduced the replication of both tested HIV-1 strains as well as the production of the mediators of inflammation IL-1β, IL-17A and CCL5, but not CCL20, in a similar way to DEX, whereas P4 had no effect on HIV-1 replication. The magnitude of both MPA and DEX-mediated responses was proportional to the length of exposure and/or administered dose. Blockage of the progesterone and glucocorticoid receptors with mifepristone abolished all observed changes in HIV-1 and cytokine production, and was associated with increased IL-22 levels in HIV-infected explants. Our data indicate that elevated doses of MPA may affect the immune responses in lymphoid tissue in a glucocorticoid-like fashion with an immediate impact on local HIV-1 replication.
Topics: Child; Contraceptive Agents, Hormonal; Female; HIV Infections; HIV-1; Humans; Lymphoid Tissue; Male; Medroxyprogesterone Acetate; Virus Replication
PubMed: 34835109
DOI: 10.3390/v13112303 -
Heliyon Dec 2023Canine Pyometra, also known as cystic endometrial hyperplasia complex, is a common reproductive issue in bitches. This study aimed to identify associated risk factors,...
Canine Pyometra, also known as cystic endometrial hyperplasia complex, is a common reproductive issue in bitches. This study aimed to identify associated risk factors, hematological variation, bacteria involved, and the most potent anti-bacterial against bacterial isolates of canine pyometra. Forty-five bitches of different habitats, breeds, and ages infected with pyometra were included in the study. The samples were cultured to isolate bacteria associated with the pyometra and antibiotic sensitivity was done for each bacterial isolates to get antibiogram. The study findings showed that potential risk factors such as age group, medroxyprogesterone acetate administration, and changes in the white blood cells parameters were significantly associated (P < 0.05) with the type of pyometra. Closed cervix pyometra in dogs showed significantly higher prevalence of clinical signs including depression, vomiting, abdominal enlargement, and fever compared to the open cervix pyometra. Low levels of red blood cells, pack cell volume, and hemoglobin indicated that the pyometra-infected dogs were more likely to have normocytic, normochromic, and non-regenerative anemia. Pyometra was attributed to an increase in AST (Aspertate aminotransferase), ALT (Alanine transaminase), ALP (Alkaline phosphatase), BUN (Blood Urea Nitrogen), and Creatinine while a decrease in serum albumin. Of the all bacterial isolates, (35.55%) was the most common pathogen isolated from canine pyometra, followed by spp. (26.66%). and spp. were susceptible to Imipenem, Amikacin, and Gentamicin while highly resistant to Ampicillin and Erythromycin. Imipenem, Amikacin, and Gentamicin were the most sensitive antibiotics, while Ampicillin and Erythromycin were the most resistant antibiotics for the bacterial strain isolated from canine pyometra. Multidrug resistant was observed in 26 of the isolated bacteria, indicating acquired resistance due to improper and uncontrolled use. Hence early diagnosis and close monitoring of antimicrobial susceptibility before therapeutic intervention is indispensable in preventing the global threat of antimicrobial resistance.
PubMed: 38076069
DOI: 10.1016/j.heliyon.2023.e22368 -
Climacteric : the Journal of the... Aug 2021The Women's Health Initiative Memory Study reported that older women using conjugated equine estrogens hormone therapy (HT) with or without medroxyprogesterone acetate... (Review)
Review
The Women's Health Initiative Memory Study reported that older women using conjugated equine estrogens hormone therapy (HT) with or without medroxyprogesterone acetate were at increased risk for probable dementia and smaller brain volumes. These adverse effects were greatest among women who had type 2 diabetes mellitus (T2DM) at baseline or who developed the disease during follow-up. This review summarizes existing literature from randomized trials, observational studies, and preclinical studies to provide a fundamental understanding of the effects of the interaction between T2DM and HT on cognitive and metabolic health changes in brain aging.
Topics: Aged; Aging; Brain; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Estradiol; Humans
PubMed: 33586564
DOI: 10.1080/13697137.2021.1877652 -
Scientific Reports Jan 2023To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing...
To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
Topics: Female; Humans; Chromatography, Liquid; Pilot Projects; Tandem Mass Spectrometry; Levonorgestrel; Medroxyprogesterone Acetate; Contraceptives, Oral, Combined
PubMed: 36604469
DOI: 10.1038/s41598-022-24215-4 -
Contraception Jul 2023Self-administered subcutaneous (SC) depot medroxyprogesterone acetate (DMPA) can improve contraception access by eliminating a health center visit for administration....
OBJECTIVES
Self-administered subcutaneous (SC) depot medroxyprogesterone acetate (DMPA) can improve contraception access by eliminating a health center visit for administration. For patients at our New York City health centers who were offered a switch to self-administered DMPA-SC at the onset of the coronavirus 2019 (COVID-19) pandemic, we sought to understand their experience of choosing to switch, of accessing and using the method, and their method satisfaction.
STUDY DESIGN
Individual interview study of 22 patients using intramuscular DMPA prior to the start of the pandemic. All had a telehealth visit to discuss switching to self-administered DMPA-SC and received a DMPA-SC prescription during the first months of COVID-19. We used a grounded theory analysis approach.
RESULTS
Respondents viewed switching to self-administered DMPA-SC as a decision they had to make if they wanted to continue DMPA. Most respondents experienced logistical challenges acquiring DMPA-SC from their pharmacy. Issues around convenience were important to respondents; however what respondents found convenient varied. Despite all this, respondents appreciated having the option of DMPA-SC and felt it to be overall empowering.
CONCLUSIONS
This study exploring patients' experience with self-administered DMPA-SC during the initial year of the COVID-19 pandemic found that, notwithstanding initial hesitation about self-administered injections and logistical challenges getting the SC formulation, many found the experience of trying self-administered DMPA-SC to be empowering and appreciated having this option. Thus, self-administered DMPA-SC should be included in clinicians' routine contraception counseling and provision, insurance companies should cover DMPA-SC without requiring prior authorization, and pharmacies should consistently stock DMPA-SC.
IMPLICATIONS
Self-administered DMPA-SC is an acceptable contraception option that provides an opportunity to maintain contraception access while eliminating need for an in-person visit. Thus, self-administered DMPA-SC should be included in clinicians' routine contraception counseling and provision, insurance companies need to cover this contraceptive without need for prior authorization, and pharmacies should consistently stock DMPA-SC.
Topics: Female; Humans; Medroxyprogesterone Acetate; Contraceptive Agents, Female; Pandemics; Patient Satisfaction; COVID-19; Injections, Subcutaneous
PubMed: 36931548
DOI: 10.1016/j.contraception.2023.110008 -
American Journal of Reproductive... Sep 2021Access to safe, effective, and affordable contraception is important for women's health and essential to mitigate maternal and fetal mortality rates. The progestin-based... (Review)
Review
BACKGROUND
Access to safe, effective, and affordable contraception is important for women's health and essential to mitigate maternal and fetal mortality rates. The progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) is a popular contraceptive choice with a low failure rate and convenient administration schedule.
AIM
In this review, we compiled observational data from human cohorts that examine how DMPA influences the mucosal biology of the female genital tract (FGT) that are essential in maintaining vaginal health, including resident immune cells, pro-inflammatory cytokines, epithelial barrier function, and the vaginal microbiome MATERIALS AND METHODS: This review focused on the recent published literature published in 2019 and 2020.
RESULTS
Recent longitudinal studies show that DMPA use associates with an immunosuppressive phenotype, increase in CD4+CCR5+ T cells, and alterations to growth factors. In agreement with previous meta-analyses, DMPA use is associated with minimal effects of the composition of the vaginal microbiome. Cross-sectional studies associate a more pro-inflammatory relationship with DMPA, but these studies are confounded by inherent weaknesses of cross-sectional studies, including differences in study group sizes, behaviors, and other variables that may affect genital inflammation.
DISCUSSION & CONCLUSION
These recent results indicate that the interactions between DMPA and the vaginal mucosa are complex emphasizing the need for comprehensive longitudinal studies that take into consideration the measurement of multiple biological parameters.
Topics: Contraceptive Agents, Female; Delayed-Action Preparations; Female; Genitalia, Female; Humans; Medroxyprogesterone Acetate; Microbiota; Mucous Membrane; Vagina
PubMed: 33991137
DOI: 10.1111/aji.13455 -
Fertility and Sterility Apr 2021To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera and compare results to two injections of Depo-SubQ Provera 104 given 3 months apart.
DESIGN
Partially randomized, multicenter, parallel-group study.
SETTING
Research unit.
PATIENT(S)
Forty-two women of reproductive age with confirmed ovulatory cycle and body mass index of 18-35 kg/m.
INTERVENTION(S)
Women received a single subcutaneous injection of 150 mg (n = 24) or 300 mg (n = 9) of Depo-Provera or two injections of Depo-SubQ Provera 104 (n = 9).
MAIN OUTCOME MEASURE(S)
Suppression of ovulation as measured by progesterone, serum medroxyprogesterone acetate concentrations, and estimated pharmacokinetics parameters.
RESULT(S)
No ovulations were observed during 7 months after a single injection of 150 or 300 mg Depo-Provera. The 150 mg group had a similar C as observed over two injection cycles of Depo-SubQ Provera 104 and a similar 6-month trough concentration as the 3-month trough of Depo-SubQ Provera 104.
CONCLUSION(S)
Our pharmacodynamics and pharmacokinetics data provide proof of concept that Depo-Provera (150 mg) may be an effective contraceptive method when injected subcutaneously every 6 months, with up to a 4-week grace period for reinjections.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02456584.
Topics: Adult; Contraceptive Agents, Female; Female; Humans; Injections, Subcutaneous; Medroxyprogesterone Acetate; Ovulation
PubMed: 33485608
DOI: 10.1016/j.fertnstert.2020.11.002 -
Steroids Jun 2022The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable...
The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable contraceptive Depo-MPA (DMPA), has off-target effects via the GR, which may result in side-effects in endocrine therapy. However, very little is known about the GR activity of other progestins used in endocrine therapy. This study compared GR activities for several progestins, using whole cell binding, dose-response, and GR phosphorylation assays, in both a cell line model and peripheral blood mononuclear cells (PBMCs). MPA, etonogestrel (ETG) and nestorone (NES) exhibit greater relative binding affinities for the GR than levonorgestrel (LNG) and norethisterone/norethindrone (NET) and are partial GR agonists for transactivation but agonists for transrepression on synthetic promoters in COS-1 cells. MPA is a potent agonist for endogenous GR-regulated GILZ and IL6 genes in PBMCs. While ETG and NES also display agonist activity on IL6, they have little effect on GILZ. In contrast, LNG and NET exhibit little to no activity in transactivation models, while both exhibit some transrepressive activity but are generally less potent and/or efficacious than MPA. Antagonist and phosphorylation assays confirmed that MPA and NES act via the GR on endogenous genes in PBMCs. Our results suggest GR-mediated dose-dependent and gene-specific transcriptional side-effects are likely to occur at physiologically relevant concentrations in vivo for MPA, may possibly occur selectively for ETG and NES, but are unlikely to occur for LNG and NET. This suggests that these progestins will exhibit differential side-effects in endocrine therapy via the GR.
Topics: Animals; COS Cells; Chlorocebus aethiops; Glucocorticoids; Interleukin-6; Leukocytes, Mononuclear; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Progestins; Receptors, Glucocorticoid
PubMed: 35271867
DOI: 10.1016/j.steroids.2022.108998 -
Current Issues in Molecular Biology Nov 2021Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as...
Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E), and progesterone (P). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E + medroxyprogesterone acetate (MPA), a potent P receptor agonist, showed significant down-regulation of , , , , , and in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, and were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased expression in untreated human ESCs. These results collectively indicate the importance of and in ESC decidualization and highlight the role of HAND2 in repressing transcription, thereby regulating decidualization.
Topics: Adult; Biomarkers; Cells, Cultured; Decidua; Endometrium; Female; Gene Expression Regulation; Humans; Matrix Metalloproteinases; Middle Aged; Steroids; Stromal Cells; Tissue Inhibitor of Metalloproteinases; Young Adult
PubMed: 34940120
DOI: 10.3390/cimb43030146 -
Frontiers in Global Women's Health 2022Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is...
Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial.
INTRODUCTION
Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18-35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial.
METHODS
Women were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135).
RESULTS
Baseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152-455), IUD 235 (168-426) and LNG 216 (153-419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163-467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97-193) pmol/L] was significantly lower than in both IUD ( < 0.0001) and implant ( = 0.005) groups; and level in the implant group [156 (112-250) pmol/L] was significantly lower than in the IUD group ( = 0.004).
CONCLUSIONS
At 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods.
ECHO STUDY REGISTRATION
ClinicalTrials.gov, identifier: NCT02550067.
PubMed: 35669313
DOI: 10.3389/fgwh.2022.887541