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Contraception Sep 2018To assess the effect of the depot medroxyprogesterone acetate injectable (DMPA) and of the levonorgestrel (LNG) implant on genital HIV shedding among women receiving... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES
To assess the effect of the depot medroxyprogesterone acetate injectable (DMPA) and of the levonorgestrel (LNG) implant on genital HIV shedding among women receiving antiretroviral therapy (ART).
METHODS
We randomized HIV-infected Malawian women to either DMPA or LNG implant from May 2014 to April 2015. HIV RNA was measured in cervicovaginal lavage (CVL) fluid and TearFlo Strips (TFS), and HIV DNA was measured in cells collected by CVL. We compared the frequency and magnitude of HIV genital shedding before and for 6 months after initiation of contraception and between arms among women receiving ART. We also compared genital HIV RNA levels obtained by sample type (TFS versus CVL).
RESULTS
We analyzed data for 68 HIV-infected women receiving ART: 33 randomized to DMPA and 35 randomized to the LNG implant. Overall, HIV RNA was more often detectable and the quantity was higher on TFS compared with CVL. HIV DNA was detected very rarely in CVL cell samples (4 of 360 samples). The frequency of genital shedding and the genital HIV quantity did not increase after contraceptive initiation with either DMPA or LNG implant among women receiving ART.
CONCLUSIONS
HIV-infected women receiving ART initiating contraception with either DMPA or LNG implant did not have any increase in genital HIV shedding during the first 6 months of contraceptive use. These findings are consistent with growing evidence that progestin contraception is not associated with increased HIV transmission risk from such women to their male partners. Consistent with other studies, genital HIV RNA detection was higher in TFS than in CVL fluid.
IMPLICATIONS
In this randomized trial, neither DMPA nor the LNG implant, two of the most commonly used hormonal contraceptives among African women with HIV, was associated with increased genital HIV shedding in HIV-infected women receiving ART. These findings are reassuring and add to the currently limited information available for the highly effective contraceptive, LNG implant.
Topics: Adult; Anti-Retroviral Agents; Contraceptive Agents, Female; Female; HIV; HIV Infections; Humans; Levonorgestrel; Medroxyprogesterone Acetate; Vaginal Smears; Virus Shedding
PubMed: 29746813
DOI: 10.1016/j.contraception.2018.05.001 -
Journal of Obstetrics and Gynaecology... Oct 2016The purpose of this study was to compare the effects of ormeloxifene with medroxyprogesterone acetate in patients with abnormal uterine bleeding.
PURPOSE
The purpose of this study was to compare the effects of ormeloxifene with medroxyprogesterone acetate in patients with abnormal uterine bleeding.
MATERIAL AND METHOD
440 Patients were divided into two groups. In group A, ormeloxifene was given at the dosage of 60 mg twice a week for 3 months followed by 60 mg once a week for 1 month. In group B, medroxyprogesterone acetate was given at the dosage of 10 mg twice a day from day 5 to day 25 of the menstrual cycle. At follow-ups, patients were assessed for PBAC score, endometrial thickness by USG, hemoglobin level, and the side effects of drug therapy.
RESULTS
There were 240 patients in group A and 200 in group B. Reduction in median PBAC score was 79.4 % in group A and 75 % in group B after 4 months of treatment. The mean duration of bleeding reduced to 4.8 from 9 in group A and 5 from 8.7 in group B. Mean hemoglobin was increased from 8.6 to 9.8 g % in group A and from 8.7 to 9.9 g % in group B; endometrial thickness was reduced from 7.7 mm to 6.8 mm in group A and from 7.4 mm to 6.9 mm in group B.
CONCLUSION
We conclude from this study that ormeloxifene should be considered the first choice in the management of AUB, especially in the perimenopausal age group where amenorrhea is acceptable.
PubMed: 27651636
DOI: 10.1007/s13224-015-0761-2 -
Lancet (London, England) Feb 2020
Topics: Contraception; Female; HIV Infections; Humans; Incidence; Intrauterine Devices, Copper; Levonorgestrel; Medroxyprogesterone Acetate
PubMed: 32035557
DOI: 10.1016/S0140-6736(19)33107-1 -
American Journal of Reproductive... Aug 2022Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence... (Randomized Controlled Trial)
Randomized Controlled Trial
PROBLEM
Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation.
METHODS
This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors.
RESULTS
Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines.
CONCLUSION
We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.
Topics: Contraceptive Agents, Female; Cytokines; Female; Genitalia; HIV Infections; Humans; Immunity, Innate; Inflammation; Intrauterine Devices, Copper; Levonorgestrel; Medroxyprogesterone Acetate
PubMed: 35394678
DOI: 10.1111/aji.13542 -
Scientific Reports Dec 2021Mucosal integrity in the endometrium is essential for immune protection. Since breaches or injury to the epithelial barrier exposes underlying tissue and is hypothesized...
Mucosal integrity in the endometrium is essential for immune protection. Since breaches or injury to the epithelial barrier exposes underlying tissue and is hypothesized to increase infection risk, we determined whether endogenous progesterone or three exogenous progestins (medroxyprogesterone acetate (MPA), norethindrone (NET), and levonorgestrel (LNG)) used by women as contraceptives interfere with wound closure of endometrial epithelial cells and fibroblasts in vitro. Progesterone and LNG had no inhibitory effect on wound closure by either epithelial cells or fibroblasts. MPA significantly impaired wound closure in both cell types and delayed the reestablishment of transepithelial resistance by epithelial cells. In contrast to MPA, NET selectively decreased wound closure by stromal fibroblasts but not epithelial cells. Following epithelial injury, MPA but not LNG or NET, blocked the injury-induced upregulation of HBD2, a broad-spectrum antimicrobial implicated in wound healing, but had no effect on the secretion of RANTES, CCL20 and SDF-1α. This study demonstrates that, unlike progesterone and LNG, MPA and NET may interfere with wound closure following injury in the endometrium, potentially conferring a higher risk of pathogen transmission. Our findings highlight the importance of evaluating progestins for their impact on wound repair at mucosal surfaces.
Topics: Adult; Cells, Cultured; Contraceptive Agents; Endometrium; Epithelial Cells; Female; Fibroblasts; Humans; Levonorgestrel; Medroxyprogesterone Acetate; Middle Aged; Norethindrone; Progesterone; Wound Healing
PubMed: 34853394
DOI: 10.1038/s41598-021-02681-6 -
BMC Cancer Jul 2022Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and...
Metformin attenuates the production and proliferative effects of prolactin induced by medroxyprogesterone acetate during fertility-sparing treatment for endometrial cancer.
BACKGROUND
Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin.
METHODS
In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009-2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting.
RESULTS
MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases.
CONCLUSIONS
MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment.
Topics: Endometrial Neoplasms; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Medroxyprogesterone Acetate; Metformin; Progestins; Prolactin; RNA, Messenger
PubMed: 35820883
DOI: 10.1186/s12885-022-09858-w -
Australian Prescriber Oct 2016
Review
PubMed: 27789925
DOI: 10.18773/austprescr.2016.057 -
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 -
Frontiers in Endocrinology 2023The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on...
Original delayed-start ovarian stimulation protocol with a gonadotropin-releasing hormone antagonist, medroxyprogesterone acetate, and high-dose gonadotropin for poor responders and patients with poor-quality embryos.
INTRODUCTION
The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on whether it is also effective for patients with poor-quality embryos and low rates of good blastocyst formation. Specifically, the effectiveness of delayed-start gonadotropin-releasing hormone antagonists with progesterone has not been adequately investigated. Therefore, we compared the efficacy of the original delayed-start gonadotropin-releasing hormone antagonist protocol using medroxyprogesterone acetate (MPA) and high-dose gonadotropin in patients with poor ovarian response.
METHODS
Overall, 156 patients with recurrent assisted reproductive technology failure who underwent the original protocol were included. They received cetrorelix acetate (3 mg) and MPA (10 mg) on cycle day 3, and high-dose gonadotropin was initiated on day 11. When the leading follicle reached 14 mm, ganirelix acetate (0.25 mg) was administered until the trigger day. The number of oocytes retrieved, metaphase II (MII) oocytes, two pronuclear (2PN) zygotes, and good blastocysts and live birth rates were compared between the previous (Cycle A) and original (Cycle B) cycles in three groups (Group A, all patients; Group B, poor responders; and Group C, patients with poor-quality embryos).
RESULTS
In Group A (n=156), the number of MII oocytes (3.6 ± 3.3 versus 4.5 ± 3.6), 2PN zygotes (2.8 ± 2.9 versus 3.8 ± 3.1), good blastocysts (0.5 ± 0.9 versus 1.2 ± 1.6), and live birth rates (0.6 versus 24.4) significantly increased in Cycle B. Similar results were obtained in Group B (n=83; 2PN zygotes [1.7 ± 1.7 versus 2.3 ± 1.8], good blastocysts [0.4 ± 0.7 versus 0.9 ± 1.3], live birth rates [0 versus 18.1]) and Group C (n=73; MII oocytes [5.1 ± 3.8 versus 6.6 ± 4.0], 2PN zygotes [4.0 ± 3.4 versus 5.4 ± 3.4], good blastocysts [0.7 ± 1.1 versus 1.6 ± 1.9], and live birth rates [1.4 versus 31.5]).
CONCLUSION
This original protocol increased the number of MII oocytes retrieved, 2PN zygotes, good blastocysts, and live birth rates in both poor responders and in patients with poor-quality embryos.
Topics: Pregnancy; Female; Humans; Medroxyprogesterone Acetate; Pregnancy Rate; Gonadotropins; Gonadotropin-Releasing Hormone; Ovulation Induction; Hormone Antagonists
PubMed: 38027155
DOI: 10.3389/fendo.2023.1277873 -
Contraception Nov 2018As low- and middle-income countries (LMICs) consider adding self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to their contraceptive method...
OBJECTIVE
As low- and middle-income countries (LMICs) consider adding self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to their contraceptive method mix, learning about family planning clients' and providers' experiences with self-injectable DMPA-SC during trials will inform introduction and scale-up efforts.
STUDY DESIGN
We conducted semistructured interviews with 30 randomly selected adult women enrolled in the self-administration group of a 12-month randomized controlled trial studying DMPA-SC continuation rates in rural Malawi. We asked about their experiences learning to self-inject, self-injecting, remembering when to reinject, and storing and disposing of DMPA-SC. We also interviewed 12 providers - clinic-based providers (CBPs) and community-based health surveillance assistants (HSAs) - who trained clients to self-inject DMPA-SC during the trial. We asked about their experiences training and supporting women to self-inject DMPA-SC during the trial and their recommendations for scale-up of self-administered DMPA-SC.
RESULTS
Clients and providers reported positive experiences with DMPA-SC self-injection. Clients felt that DMPA-SC self-injection saved them time and money, and providers felt that it reduced their workload and saved them time. We found that both CBPs and HSAs successfully trained clients to self-inject DMPA-SC and that clients safely and appropriately stored and disposed of DMPA-SC.
CONCLUSIONS
Our findings contribute to the growing body of evidence of the feasibility of DMPA-SC self-injection in LMIC settings. We recommend that providers plan to train clients for at least 30min, emphasize the activating and injecting steps during training, use up to four practice injections per client trained and give self-injectors calendars to help them remember when to reinject.
IMPLICATIONS
DMPA-SC self-administration should be made available in LMIC settings, but because it is a new practice, implementation guidance is needed. We offer practical recommendations for introducing and scaling up DMPA-SC self-administration based on clients' and providers' experiences during a trial investigating this practice in Malawi.
Topics: Adult; Contraceptive Agents, Female; Female; Humans; Injections, Subcutaneous; Malawi; Medroxyprogesterone Acetate; Self Administration; Young Adult
PubMed: 29706227
DOI: 10.1016/j.contraception.2018.02.011