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Current HIV/AIDS Reports Aug 2023The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although... (Review)
Review
PURPOSE OF REVIEW
The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although DMPA-IM provides reliable contraception, potential effects on the female genital tract (FGT) mucosa have raised concern, including risk of HIV infection. This review summarises and compares evidence from observational cohort studies and the randomised Evidence for Contraceptive Options in HIV Outcomes (ECHO) Trial.
RECENT FINDINGS
Although previous observational studies found women using DMPA-IM had higher abundance of bacterial vaginosis (BV)-associated bacteria, increased inflammation, increased cervicovaginal HIV target cell density, and epithelial barrier damage, sub-studies of the ECHO Trial found no adverse changes in vaginal microbiome, inflammation, proteome, transcriptome, and risk of viral and bacterial STIs, other than an increase in Th17-like cells. Randomised data suggest that DMPA-IM use does not adversely change mucosal endpoints associated with acquisition of infections. These findings support the safe use of DMPA-IM in women at high risk of acquiring STIs, including HIV.
Topics: Female; Humans; Medroxyprogesterone Acetate; Contraceptive Agents, Female; HIV Infections; Bacteria; Inflammation; Mucous Membrane; Observational Studies as Topic
PubMed: 37341916
DOI: 10.1007/s11904-023-00662-0 -
Frontiers in Global Women's Health 2024Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced...
Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced cardiovascular disease. This led to a large-scale study called the Women's Health Initiative (WHI) that was conducted to show the cardiovascular benefits of HRT. This study was suspended early because of adverse side effects. The USFDA responded by slapping a "black box" warning on all HRT products. USFDA-approved bioidentical HRT formulations are safe and effective. We propose that these formulations have the "black box" warning removed so that doctors feel more confident in prescribing these products for symptoms of menopause and chronic conditions such as cardiovascular health. We propose eliminating the sale of products containing medroxyprogesterone acetate (MPA) because of the increased risk of heart attacks and breast cancers associated with this medication.
PubMed: 38832110
DOI: 10.3389/fgwh.2024.1397123 -
Women's Health (London, England) Nov 2015
Topics: Estrogen Replacement Therapy; Evidence-Based Medicine; Female; Humans; Menopause
PubMed: 26335958
DOI: 10.2217/whe.15.37 -
American Journal of Reproductive... Mar 2020Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after...
PROBLEM
Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En).
METHOD OF STUDY
Peripheral blood mononuclear cells collected from women aged 18-34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net-En (n = 36) and from women initiating copper intrauterine device (CU-IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4).
RESULTS
Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD-1+ (P < .001) and CD8+PD-1+ (P < .001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net-En initiation (P < .001 and P < .001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD-1+ (P = .083) and CD8+PD-1+ (P = .936) compared to baseline.
CONCLUSION
Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.
Topics: Adolescent; Adult; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; CTLA-4 Antigen; Cells, Cultured; Contraceptive Agents, Female; Female; Humans; Immunophenotyping; Lymphocyte Activation; Medroxyprogesterone Acetate; Norethindrone; Programmed Cell Death 1 Receptor; Young Adult
PubMed: 31729087
DOI: 10.1111/aji.13210 -
Therapeutic Advances in Musculoskeletal... Oct 2014Drug-induced osteoporosis is a significant health problem and many physicians are unaware that many commonly prescribed medications contribute to significant bone loss... (Review)
Review
Drug-induced osteoporosis is a significant health problem and many physicians are unaware that many commonly prescribed medications contribute to significant bone loss and fractures. In addition to glucocorticoids, proton pump inhibitors, selective serotonin receptor inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, aromatase inhibitors, androgen deprivation therapy, heparin, calcineurin inhibitors, and some chemotherapies have deleterious effects on bone health. Furthermore, many patients are treated with combinations of these medications, possibly compounding the harmful effects of these drugs. Increasing physician awareness of these side effects will allow for monitoring of bone health and therapeutic interventions to prevent or treat drug-induced osteoporosis.
PubMed: 25342997
DOI: 10.1177/1759720X14546350 -
BMC Women's Health Mar 2024Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.
BACKGROUND
Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods.
METHODS
In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months.
RESULTS
We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p < 0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p < 0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p < 0.001 and than DMPA (mean percentage difference - 39.45, p < 0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001).
CONCLUSIONS
This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study.
ECHO TRIAL REGISTRATION
ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.
Topics: Female; Humans; Acne Vulgaris; Androgens; Contraceptive Agents, Female; Intrauterine Devices, Copper; Levonorgestrel; Medroxyprogesterone Acetate; Progestins; Sex Hormone-Binding Globulin; Testosterone; Adolescent; Young Adult; Adult
PubMed: 38459552
DOI: 10.1186/s12905-024-02990-8 -
Brazilian Journal of Medical and... 2018Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic... (Review)
Review
Because of weight gain, women often discontinue hormonal contraception, especially depot medroxyprogesterone acetate (DMPA). Our objective was to conduct a systematic review of studies describing dietary intake or eating behavior in DMPA users to understand whether the use of DMPA is associated with changes in dietary habits and behaviors leading to weight gain. We searched the PubMed, POPLINE, CENTRAL Cochrane, Web of Science, and EMBASE databases for reports published in English between 1980 and 2017 examining dietary intake or eating behavior in healthy women in reproductive age and adolescents using DMPA (150 mg/mL). Of the 749 publications screened, we excluded 742 due to duplicates (96), not addressing the key research question (638), not reporting dietary intake data (4), and not evaluating the relationship of body weight and dietary or eating behaviors (4). We identified seven relevant studies, including one randomized placebo-controlled trial, one non-randomized paired clinical trial, and five cohort studies. The randomized trial found no association and the other reports were inconsistent. Findings varied from no change in dietary intake or eating behavior with DMPA use to increased appetite in the first six months of DMPA use. Few studies report dietary intake and eating behavior in DMPA users and the available data are insufficient to conclude whether DMPA use is associated with changes in dietary habits or behavior leading to weight gain.
Topics: Body Mass Index; Clinical Trials as Topic; Contraceptive Agents, Female; Energy Intake; Feeding Behavior; Female; Humans; Medroxyprogesterone Acetate; Weight Gain
PubMed: 29694506
DOI: 10.1590/1414-431x20187575 -
Clinical Pharmacology and Therapeutics Oct 2021Depot medroxyprogesterone acetate is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As...
Depot medroxyprogesterone acetate is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As medroxyprogesterone acetate is a cytochrome P450 (CYP3A4) substrate, drug-drug interactions (DDIs) with antiretroviral or antituberculosis treatment may lead to subtherapeutic medroxyprogesterone acetate concentrations (< 0.1 ng/mL), resulting in contraception failure, when depot medroxyprogesterone is dosed at 12-week intervals. A pooled population pharmacokinetic analysis with 744 plasma medroxyprogesterone acetate concentrations from 138 women treated with depot medroxyprogesterone and antiretroviral/antituberculosis treatment across three clinical trials was performed. Monte Carlo simulations were performed to predict the percentage of participants with subtherapeutic medroxyprogesterone acetate concentrations and to derive alternative dosing strategies. Medroxyprogesterone acetate clearance increased by 24.7% with efavirenz coadministration. Efavirenz plus antituberculosis treatment (rifampicin + isoniazid) increased clearance by 52.4%. Conversely, lopinavir/ritonavir and nelfinavir decreased clearance (28.7% and 15.8%, respectively), but lopinavir/ritonavir also accelerated medroxyprogesterone acetate's appearance into the systemic circulation, thus shortening the terminal half-life. A higher risk of subtherapeutic medroxyprogesterone acetate concentrations at Week 12 was predicted on a typical 60-kg woman on efavirenz (4.99%) and efavirenz with antituberculosis treatment (6.08%) when compared with medroxyprogesterone acetate alone (2.91%). This risk increased in women with higher body weight. Simulations show that re-dosing every 8 to 10 weeks circumvents the risk of subtherapeutic medroxyprogesterone acetate exposure associated with these DDIs. Dosing depot medroxyprogesterone every 8 to 10 weeks should eliminate the risk of subtherapeutic medroxyprogesterone acetate exposure caused by coadministered efavirenz and/or antituberculosis treatment, thus reducing the risk of contraceptive failure.
Topics: Alkynes; Anti-Retroviral Agents; Antitubercular Agents; Benzoxazines; Contraceptive Agents, Hormonal; Contraceptive Effectiveness; Cyclopropanes; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Delayed-Action Preparations; Drug Administration Schedule; Drug Combinations; Drug Interactions; Female; HIV Infections; Humans; Isoniazid; Lopinavir; Medroxyprogesterone Acetate; Nelfinavir; Rifampin; Ritonavir; Tuberculosis
PubMed: 34151439
DOI: 10.1002/cpt.2324 -
AIDS (London, England) Feb 2022We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA...
OBJECTIVE
We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STIs) that are known to increase HIV susceptibility in women.
DESIGN
Two macaque models of increasing vaginal STI severity were used for efficacy assessment.
METHODS
The first study (n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis and Trichomonas vaginalis. Six animals were CAB-LA treated and five were controls. The second study (n = 9) included a triple STI model with repeated exposures to C. trachomatis, T. vaginalis and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared with untreated controls over time.
RESULTS
All six CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges, while the untreated animals became SHIV-infected after a median of two challenges (log-rank P < 0.001) or one challenge (log-rank P = 0.002), respectively. Both models recapitulated human STI disease, with vaginal discharge, ulcers, and seroconversion.
CONCLUSION
In these high and sustained susceptibility models spanning more than 3 months, CAB-LA maintained complete efficacy, demonstrating robustness of the CAB-LA dose used in clinical trials, and suggesting its insensitivity to multiple STIs and DMPA.
Topics: Animals; Diketopiperazines; Female; HIV Infections; Humans; Macaca; Medroxyprogesterone Acetate; Pyridones; Sexually Transmitted Diseases; Simian Acquired Immunodeficiency Syndrome
PubMed: 34482355
DOI: 10.1097/QAD.0000000000003059 -
Journal of Animal Science Jun 2022A previous study reported that a 400-mg dose of medroxyprogesterone acetate (MPA) reduced male reindeer aggression and blocked development of secondary sexual...
A previous study reported that a 400-mg dose of medroxyprogesterone acetate (MPA) reduced male reindeer aggression and blocked development of secondary sexual characteristics but did not completely impair fertility. Here we have repeated that protocol in two separate trials. In 2017, tissues and blood samples, collected from MPA and control (CTL) reindeer bulls, euthanized at 30 and 60 d post-treatment were used to evaluate testes histology and morphometrics, cfos activity in the brain and androgen levels. While testes weight tended to decline from August to September in both groups, indices of spermatogenesis remained high. By September, indices of spermatogenesis were declining in both groups with sperm density lower (P = 0.05) in MPA compared to CTL bulls. Aug CTL bulls had the highest concentrations of androstenedione (A4) (P = 0.009) and testosterone (T) (P = 0.08), whereas these androgens were baseline in Aug MPA bulls. By September, A4 and T levels in CTL bulls declined to levels measured in MPA bulls. Cfos activity had a greater number (P = 0.02) of cfos positive neurons in the central amygdala in MPA compared to CTL bulls, suggesting a heightened fear response among the MPA bulls. In the second trial (2019), MPA-treated bulls, with (E, n = 4) and without (IE, n = 4) breeding experience, were blood sampled at key points from July through September when they were put in individual harems with estrous-synchronized cows. Concentrations of T were greatest (P < 0.001) among E bulls prior to MPA treatment but 1 mo after treatment, both T and A4 were baseline in all eight reindeer. Semen collected by electroejaculation at 60 d post-MPA treatment revealed only minor differences in sperm abnormalities between E and IE bulls using both fresh and frozen/thawed semen. Only three bulls (2 E and 1 IE) sired offspring. Breeding success was not related to previous breeding experience, body weight, or bull age. The failure of some MPA bulls to breed appears to be a behavioral, not a physiological, limitation. Limited application of MPA is clearly a useful tool for managing rut-aggression in non-breeding reindeer. However, the possibility that semen could be collected from MPA-treated bulls using restraint and mild sedation rather than general anesthesia should be investigated. This could improve the quality of semen collection while enhancing the safety of both handlers and animals.
Topics: Androgens; Animals; Brain; Cattle; Female; Male; Medroxyprogesterone Acetate; Plant Breeding; Reindeer; Semen Analysis; Testis
PubMed: 35648129
DOI: 10.1093/jas/skac106