-
Contraception: X 2021To examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle...
OBJECTIVE
To examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development.
STUDY DESIGN
We assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14 mm, 15-17 mm and ≥ 18 mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24 h after DMPA administration to examine against ovulatory outcomes.
RESULTS
Twenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14 mm: 0/10 (0%); 15-17 mm: 3/10 (30%); ≥ 18 mm: 6/6 (100%); p < .01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7 IU/L (mean 49.0 IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression.
CONCLUSION
DMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge.
IMPLICATIONS
DMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.
PubMed: 33367229
DOI: 10.1016/j.conx.2020.100050 -
International Journal of Molecular... Jun 2023Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled...
Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that levels are induced by medroxyprogesterone acetate (MPA) and etonogestrel (ETO) in cultured HESCs. We hypothesized that pLARC-induced ZBTB16 expression contributes to HESC decidualization, whereas prolonged enhancement of ZBTB16 levels triggers an inflammatory milieu by inducing pro-inflammatory gene expression and tissue-factor-mediated thrombin generation in decidualized HESCs. Thus, ZBTB16 immunostaining was performed in paired endometria from pre- and post-depo-MPA (DMPA)-administrated women and oophorectomized guinea pigs exposed to the vehicle, estradiol (E), MPA, or E + MPA. The effect of progestins including MPA, ETO, and levonorgestrel (LNG) and estradiol + MPA + cyclic-AMP (E + MPA + cAMP) on levels were measured in HESC cultures by qPCR and immunoblotting. The regulation of levels by MPA was evaluated in glucocorticoid-receptor-silenced HESC cultures. was overexpressed in cultured HESCs for 72 h followed by a ± 1 IU/mL thrombin treatment for 6 h. DMPA administration in women and MPA treatment in guinea pigs enhanced ZBTB16 immunostaining in endometrial stromal and glandular epithelial cells. The findings indicated that: (1) ZBTB16 levels were significantly elevated by all progestin treatments; (2) MPA exerted the greatest effect on levels; (3) MPA-induced expression was inhibited in glucocorticoid-receptor-silenced HESCs. Moreover, overexpression in HESCs significantly enhanced prolactin (), insulin-like growth factor binding protein 1 (), and tissue factor () levels. Thrombin-induced interleukin 8 ( and prostaglandin-endoperoxide synthase 2 ( mRNA levels in control-vector-transfected HESCs were further increased by overexpression. In conclusion, these results supported that ZBTB16 is enhanced during decidualization, and long-term induction of ZBTB16 expression by pLARCs contributes to thrombin generation through enhancing tissue factor expression and inflammation by enhancing and levels in decidualized HESCs.
Topics: Female; Humans; Animals; Guinea Pigs; Progestins; Interleukin-8; Thrombin; Contraceptive Agents; Thromboplastin; Glucocorticoids; Cyclooxygenase 2; Endometrium; Estradiol; Inflammation; Stromal Cells; Cells, Cultured; Decidua; Medroxyprogesterone Acetate
PubMed: 37445713
DOI: 10.3390/ijms241310532 -
Contraception Sep 2016Depot medroxyprogesterone acetate (DMPA), a progestogen-only contraceptive injectable, has traditionally been formulated as a crystalline suspension delivered... (Review)
Review
CONTEXT
Depot medroxyprogesterone acetate (DMPA), a progestogen-only contraceptive injectable, has traditionally been formulated as a crystalline suspension delivered intramuscularly (IM) at a dose of 150mg/1.0mL. A new, lower dose formulation of DMPA (104mg/0.65mL) has been developed for subcutaneous administration (SC). Given its increasing global availability and public health relevance, DMPA-SC was prioritized for inclusion as a new method referenced in the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use (MEC), 5th Edition.
OBJECTIVE
This systematic review evaluated the published peer-reviewed literature regarding the safety of DMPA-SC among women with various characteristics or medical conditions. Results of this review informed the decision-making of a WHO Guideline Development Group in order to include recommendations on contraceptive eligibility within the revised MEC.
METHODS
We searched PubMed and Cochrane Library databases to identify all relevant evidence published in peer-reviewed journals regarding the safety of DMPA-SC when used by women of reproductive age, particularly those with select characteristics or conditions specified in the MEC, from inception through June 2015. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force.
RESULTS
Fourteen studies met criteria for inclusion. Ten reported results relevant to DMPA users of varying age or with obesity, endometriosis or HIV; four compared the safety of DMPA-SC and DMPA-IM when used by general populations of healthy women. A randomized trial evaluating changes in bone mineral density among adult DMPA-SC and DMPA-IM users demonstrated no differences at 2years of follow-up. Limited evidence reported no consistent differences in weight change or bleeding patterns according to age; however, adolescents (<18years) were not included in any studies. Similar contraceptive efficacy, weight change, bleeding patterns and occurrence of other adverse effects among obese and nonobese DMPA-SC users were observed. Women with endometriosis using DMPA-SC over 6months had minimal decreases in bone mineral density, weight gain, few serious adverse events and experienced improved pain symptoms. Women living with HIV tolerated injection of DMPA-SC with rare complications. DMPA-SC and DMPA-IM also show therapeutic equivalence and similar effects on weight gain, changes in bleeding patterns and reports of other adverse effects when these different delivery systems were used by general populations of women.
CONCLUSION
Evidence for use of DMPA-SC by women with select conditions and characteristics including age, obesity, endometriosis or HIV demonstrates that this method can generally be used safely in these contexts. Further, DMPA-SC and DMPA-IM appear to be therapeutically equivalent with similar safety profiles when used by healthy women.
Topics: Bone Density; Contraceptive Agents, Female; Delayed-Action Preparations; Endometriosis; Female; HIV Infections; Humans; Injections, Intramuscular; Injections, Subcutaneous; Medroxyprogesterone Acetate; Obesity; Pain; Patient Satisfaction; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Weight Gain; World Health Organization
PubMed: 26874275
DOI: 10.1016/j.contraception.2016.02.003 -
Cureus Apr 2024Introduction 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,...
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.
PubMed: 38779259
DOI: 10.7759/cureus.58700 -
Systematic Reviews Jul 2023Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for... (Review)
Review
BACKGROUND
Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for improving contraceptive access, continuation, and autonomy. However, there are challenges in rolling out this new efficacious intervention, and major implementation problems have been encountered during scale-up.
OBJECTIVE
To describe the implementation strategies to scale up self-administered DMPA-SC and the barriers, facilitators, and outcomes of these programs.
METHOD
Recent guidelines, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, were used to design and report this review. An article or report was eligible for inclusion if it reported interventions that could scale up self-administered DMPA-SC implementation or its facilitators, barriers, or outcomes. We searched six electronic databases and the grey literature for eligible articles and reports. Two reviewers independently screened the document titles, abstracts, and full texts to identify eligible documents. Data were extracted using structured forms. Using the Effective Practice and Organization of Care (EPOC) taxonomy of health systems framework for thematic analysis, data were presented in a narrative approach.
RESULTS
Of the 755 retrieved documents, 34 were included in this review. Most of the documents included were multi-country reports (n = 14), and all documents were published within the last 5 years (2018-2021). This review identified documents that reported interventions in all EPOC domains. The most-reported interventions were: task-sharing amongst health workforce cadres, engaged leadership, encouraging policies, training and education, DMPA-SC demand generation, integration into existing programs, improved funding mechanisms, collaboration with development partners, and supply chain strengthening. The main barriers were suboptimal funding, inadequate human resources, and poor logistics supply of DMPA-SC. There was minimal evidence of scale-up outcomes.
CONCLUSION
This scoping review reported a wide range of interventions employed by countries and programs to scale up DMPA-SC self-administration but minimal evidence of the scale-up outcomes. Evidence from this review can help design better programs that improves access to quality family planning services to achieve the Sustainable Development Goals (SDG) targets 3.7. However, efforts should focus on rigorous implementation research that assess scaled up self-administered DMPA-SC interventions and report their outcomes.
REGISTRATION
The protocol for this review was registered in the protocols.io repository ( https://www.protocols.io/view/a-protocol-for-a-scoping-review-of-implementation-x54v9yemmg3e/v1 ).
Topics: Female; Humans; Contraception; Contraceptive Agents, Female; Injections, Subcutaneous; Medroxyprogesterone Acetate; Self Administration
PubMed: 37403147
DOI: 10.1186/s13643-023-02216-2 -
Disease Models & Mechanisms Aug 2018The role of sex hormones in regulating immune responses in the female genital tract has been recognized for decades. More recently, it has become increasingly clear that... (Review)
Review
The role of sex hormones in regulating immune responses in the female genital tract has been recognized for decades. More recently, it has become increasingly clear that sex hormones regulate susceptibility to sexually transmitted infections through direct and indirect mechanisms involving inflammation and immune responses. The reproductive cycle can influence simian/human immunodeficiency virus (SHIV) infections in primates and HIV-1 infection in cervical tissues from women. Exogenous hormones, such as those found in hormonal contraceptives, have come under intense scrutiny because of the increased susceptibility to sexually transmitted infections seen in women using medroxyprogesterone acetate, a synthetic progestin-based contraceptive. Recent meta-analyses concluded that medroxyprogesterone acetate enhanced HIV-1 susceptibility in women by 40%. In contrast, estradiol-containing hormonal contraceptives were not associated with increased susceptibility and some studies reported a protective effect of estrogen on HIV/SIV infection, although the underlying mechanisms remain incompletely understood. Recent studies describe a key role for the vaginal microbiota in determining susceptibility to sexually transmitted infections, including HIV-1. While spp.-dominated vaginal microbiota is associated with decreased susceptibility, complex microbiota, such as those seen in bacterial vaginosis, correlates with increased susceptibility to HIV-1. Interestingly, sex hormones are inherently linked to microbiota regulation in the vaginal tract. Estrogen has been postulated to play a key role in establishing a -dominated microenvironment, whereas medroxyprogesterone acetate is linked to hypo-estrogenic effects. The aim of this Review is to contribute to a better understanding of the sex-hormone-microbiome-immunity axis, which can provide key information on the determinants of HIV-1 susceptibility in the female genital tract and, consequently, inform HIV-1 prevention strategies.
Topics: Disease Susceptibility; Female; Gonadal Steroid Hormones; HIV Infections; Humans; Immunity; Microbiota; Vagina
PubMed: 30154116
DOI: 10.1242/dmm.035147 -
Ovariectomized mice and postmenopausal women exhibit analogous loss of genital epithelial integrity.Tissue Barriers Apr 2021Roughly half of all postmenopausal women are affected by the genitourinary syndrome of menopause (GSM). Symptoms of GSM, including vaginal irritation and dyspareunia,...
Roughly half of all postmenopausal women are affected by the genitourinary syndrome of menopause (GSM). Symptoms of GSM, including vaginal irritation and dyspareunia, occur as reduced estrogen (E) production elicits loss of elasticity and other changes in genital tract tissue. While the use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) likewise lowers serum E concentrations in reproductive age women and is associated with decreased genital levels of the cell-cell adhesion molecules desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and impaired genital epithelial barrier function, the relevance of these findings to women in menopause is uncertain. Exploring the impact of menopause on genital epithelial integrity herein, we detected significantly lower levels of DSG1 and DSC1 in ectocervical tissue from menopausal and postmenopausal vs premenopausal women. Using ovariectomized (OVX) mice as a menopause model, we comparably saw significantly lower vaginal tissue levels of DSG1 and DSC1 in OVX mice vs. mice in estrus. Compared to estrus-stage mice and E-treated OVX mice, DMPA-treated ovary-intact mice and OVX mice also exhibited significantly reduced genital epithelial barrier function, greater susceptibility to genital herpes simplex virus type 2 infection, and delayed clearance of genital infection. Current studies thus identify analogous loss of genital epithelial integrity in OVX mice and menopausal and postmenopausal women. By showing that loss of genital epithelial integrity is associated with increased mouse susceptibility to bacterial and viral pathogens, our findings also prioritize the need to resolve if reduced genital epithelial integrity in postmenopausal women is a significant risk factor for genital infection.
Topics: Animals; Epithelium; Female; Genitalia, Female; Humans; Mice; Ovary
PubMed: 33427560
DOI: 10.1080/21688370.2020.1865760 -
Frontiers in Immunology 2019A synthetic progestin, medroxyprogesterone acetate (MPA), was used in a novel study to determine progestin effects on human purified macrophages and Th1, Th2, Th17, Th22...
A synthetic progestin, medroxyprogesterone acetate (MPA), was used in a novel study to determine progestin effects on human purified macrophages and Th1, Th2, Th17, Th22 cells. MPA concentrations were equivalent to those in the serum of women after 6 and 9 months of progestin use. MPA has no effect on the proliferation of PBMCs and CD4+ T cell clones induced by immobilized anti-CD3 antibodies or by antigen (streptokinase). However, MPA decreases production and mRNA expression of IL-5, IL-13, IFN-γ, T-bet, RORC, and IL-17A but increases production and mRNA expression of IL-22 by CD4+ Th22 cell clones and decreases IL-22 production by Th17 cells. MPA inhibits RORC, but not T-bet and AHR, by Th17 cells but increases AHR mRNA and T-bet expression of established CD4+ Th22 cell clones. This suggests that MPA, at concentrations equivalent to those found in the serum of women after treatment for contraception and hormone replacement therapy, can directly inhibit Th1 responses (against intracellular bacteria and viruses), Th17 (against extracellular bacteria and fungi), Th2 (against parasites) but MPA therapy increases IL-22 produced by Th22 cells mediated by an increased expression of AHR and T-bet controlling inflammation. MPA could be responsible for the tissue damage limited by IL-22 in absence of IL-17A.
Topics: Adult; Bacterial Infections; Basic Helix-Loop-Helix Transcription Factors; Cytokines; Disease Susceptibility; Female; Humans; Inflammation; Macrophages; Male; Medroxyprogesterone Acetate; Nuclear Receptor Subfamily 1, Group F, Member 3; Receptors, Aryl Hydrocarbon; Sex Factors; Signal Transduction; T-Box Domain Proteins; Th1 Cells; Th17 Cells; Virus Diseases
PubMed: 31001262
DOI: 10.3389/fimmu.2019.00642 -
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