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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 -
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 -
European Journal of Obstetrics,... Feb 2017Endometriotic lesions are associated with hormonal imbalance, including increased estrogen synthesis, metabolism and progesterone resistance. These hormonal changes... (Review)
Review
Endometriotic lesions are associated with hormonal imbalance, including increased estrogen synthesis, metabolism and progesterone resistance. These hormonal changes cause increased proliferation, inflammation, pain and infertility. Hormonal imbalances are targets for treatment. Therapeutic strategies and innovations of hormonal drugs for endometriosis are increasing. Acting on estrogen receptors are hormonal drugs decreasing systemic and local estrogen synthesis (GnRH analogs, GnRH antagonists, Aromatase inhibitors) or estrogen activity (selective estrogen receptor modulators). The progesterone resistance is counteracted by progestins (Medroxyprogesterone acetate, Dienogest, Danazol, Levonorgestrel) or by Selective progesterone receptor modulators, a class of drugs under development. The future trend will be to define new drugs to use for prolonged period of time and with poor side effects considering endometriosis a chronic disease.
Topics: Aromatase Inhibitors; Endometriosis; Female; Hormone Antagonists; Humans; Levonorgestrel; Medroxyprogesterone Acetate; Selective Estrogen Receptor Modulators; Treatment Outcome
PubMed: 27503693
DOI: 10.1016/j.ejogrb.2016.05.032 -
American Journal of Perinatology Dec 2023While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our...
OBJECTIVE
While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our objective was to evaluate the relationship between receipt of DMPA in the immediate postpartum period and postpartum depressive symptoms.
STUDY DESIGN
This retrospective cohort study included all women who received prenatal and postpartum care at academic obstetric clinics affiliated with a tertiary care institution between January 1, 2008 and December 31, 2014. All women were counseled on contraception prior to hospital discharge. DMPA was available in the hospital pharmacy, and its utilization was documented in the electronic health record. The Patient Health Questionnaire 9 (PHQ-9) was used to screen for postpartum depression for all women at all postpartum visits. A score of 10 or greater was categorized as positive. Bivariable and multivariable analyses were used to identify the association between immediate postpartum DMPA use and a positive postpartum depression screen.
RESULTS
Of the 5,073 women who met inclusion criteria, 410 (8.1%) received DMPA prior to hospital discharge. Compared with women who did not receive DMPA, women who received DMPA prior to hospital discharge were younger, more likely to identify as Black race or Latinx ethnicity, and more likely to be publicly insured. Clinical characteristics also differed. Women who received DMPA were more likely to be obese and to have experienced prenatal depressive symptoms, been diagnosed with a hypertensive disorder of pregnancy, delivered preterm, and delivered vaginally. Receipt of immediate postpartum DMPA was not associated with having a positive screen for postpartum depression in bivariable (5.4 vs. 6.0%, = 0.29) or multivariable (adjusted odds ratio 0.94, confidence interval 0.53-1.68) analyses.
CONCLUSION
Receipt of postpartum DMPA is not associated with a positive postpartum PHQ-9 screen. Concerns about precipitating postpartum depression should not preclude the utilization of DMPA as a contraceptive agent.
KEY POINTS
· Contraception is an important issue for obstetricians to address with postpartum patients.. · Concerns have been raised over the relationship between DMPA and depression.. · Our study shows that DMPA is not associated with a positive postpartum depression screen..
Topics: Pregnancy; Infant, Newborn; Humans; Female; Medroxyprogesterone Acetate; Contraceptive Agents, Female; Depression; Depression, Postpartum; Retrospective Studies; Postpartum Period
PubMed: 34775585
DOI: 10.1055/s-0041-1739431 -
Contraceptive effects on the cervicovaginal microbiome: Recent evidence including randomized trials.American Journal of Reproductive... Nov 2023Until recently, most data regarding the effects of non-barrier contraceptives on the mucosal microbiome have derived from observational studies, which are potentially... (Review)
Review
BACKGROUND
Until recently, most data regarding the effects of non-barrier contraceptives on the mucosal microbiome have derived from observational studies, which are potentially biased due to behavioral confounders that may mask their true biological effects.
METHOD OF STUDY
This narrative review summarises recent evidence of the effect of contraceptives on the cervicovaginal microbiome, emphasising data obtained through randomized trials.
RESULTS
Good quality data describe that initiation of long-acting progestin-only contraceptives, including levonorgestrel (LNG)-implant and the injectables depot-medroxyprogesterone acetate (DMPA-IM) and norethisterone enanthate (NET-EN) do not alter the mucosal microbial environment. Likewise, no strong evidence exists that the use of oral contraceptive pills (OCPs) is associated with alterations of the vaginal microbiome or increased risk of bacterial sexually transmitted infections (STIs). Limited data on the effect of intravaginal rings (IVRs) on the mucosal environment exist and show conflicting effects on the vaginal microbiota. Copper intrauterine device (Cu-IUD) initiation has been associated with bacterial vaginosis (BV) acquisition, including in a randomized trial. LNG-IUDs may have similar affects but need to be evaluated further.
CONCLUSION
Different synthetic hormones have divergent effects on the microbiome and therefore novel hormonal methods need to be rigorously evaluated. Furthermore, the addition of antiretrovirals into multipurpose technologies may alter the effects of the hormonal component. There is thus a critical need to improve our understanding of the biological effects of contraceptive hormones and delivery methods with different pharmacokinetic and chemical properties on the mucosal microbiome in rigorous trials, to inform the development of novel contraceptives and improve individual family planning guidance.
Topics: Female; Humans; Contraceptive Agents; Contraceptive Agents, Female; Hormones; Levonorgestrel; Medroxyprogesterone Acetate; Microbiota; Randomized Controlled Trials as Topic
PubMed: 37881121
DOI: 10.1111/aji.13785 -
Obstetrics and Gynecology Feb 2019Counseling about potential side effects and health benefits of contraceptive methods could facilitate continued method use and method satisfaction, yet no evidence-based...
OBJECTIVE
Counseling about potential side effects and health benefits of contraceptive methods could facilitate continued method use and method satisfaction, yet no evidence-based compilation of side effects and benefits exists to aid such counseling. Among contraceptive methods in the United States, depot medroxyprogesterone acetate (DMPA) injectables have the highest discontinuation rates, and most discontinuation is attributable to side effects. This review examines the side effects and health benefits of DMPA to inform counseling.
DATA SOURCES
We searched PubMed, POPLINE, EMBASE, Web of Science, Campbell Collaboration Library of Systematic Reviews, the Cochrane Database of Systematic Reviews, the Cochrane Center Register of Controlled Trials, and ClinicalTrials.gov.
METHODS OF STUDY SELECTION
We included English-language studies published from 1985 to 2016 that enrolled healthy, nonbreastfeeding females aged 13-49 years at risk of unintended pregnancy, compared intramuscular or subcutaneous progestin-only injectables to a contemporaneous comparison group, and addressed at least one key question: 1) What side effects are associated with progestin-only injectable contraceptive use? 2) What health benefits are associated with progestin-only injectable contraceptive use? Study quality was assessed using criteria from the U.S. Preventive Services Task Force.
TABULATION, INTEGRATION, AND RESULTS
Twenty-four studies met inclusion criteria. None were randomized controlled trials. There were 13 prospective cohort, five retrospective cohort, four case-control, and two cross-sectional studies. Studies of moderate or high risk of bias suggest an association between DMPA use and weight gain, increased body fat mass, irregular bleeding, and amenorrhea. Inconsistent evidence exists for an association between DMPA use and mood or libido changes. Limited evidence exists for an association between DMPA use and decreased risk of cancers and tubal infertility.
CONCLUSION
Higher-quality research is needed to clarify DMPA's side effects and benefits. In absence of such evidence, patient-centered counseling should incorporate the available evidence while acknowledging its limitations and recognizing the value of women's lived experiences.
Topics: Contraceptive Agents, Female; Delayed-Action Preparations; Female; Humans; Long-Acting Reversible Contraception; Medroxyprogesterone Acetate
PubMed: 30633132
DOI: 10.1097/AOG.0000000000003089 -
Archives of Gynecology and Obstetrics Jul 2023The aim of this study was to compare the effects of Dienogest and medroxyprogesterone acetate (MPA) on the recurrence of endometriosis lesions and clinical symptoms in... (Clinical Trial)
Clinical Trial
PURPOSE
The aim of this study was to compare the effects of Dienogest and medroxyprogesterone acetate (MPA) on the recurrence of endometriosis lesions and clinical symptoms in women undergoing laparoscopic surgery.
METHODS
This single center clinical trial was conducted among 106 women with endometriosis undergoing laparoscopic surgery who candidate receiving post-surgery hormone therapy. Participants were allocated to two groups. The first group received Dienogest pills (2 mg) daily for the first three months and then cyclic for three months afterward. The second group received MPA pills twice daily (10 mg) for three months and then cyclic for the next three months. Six months after the intervention, the rate of endometriosis recurrence, the size of endometriosis lesions and pelvic pain were assess and compared between two groups.
RESULTS
Finally, data were evaluated based on 48 and 53 women in the Dienogest and MPA groups, respectively. After 6 months follow-up assessments the pelvic pain score was significantly lower in Dienogest group than MPA group (P < 0.001). There was not statistically difference between two groups in terms of recurrence rate of endometriosis (P = 0.4). Although the size of endometriosis cyst recurrence was smaller in Dienogest group compared to MPA group (P = 0.02).
CONCLUSIONS
The findings showed that Dienogest treatment has better effect in reducing pelvic pain and the mean size of the recurrent endometriosis lesions after endometriosis laparoscopic surgery when compared to MPA treatment. Although the recurrent rate of endometriosis was similar between these treatments.
Topics: Female; Humans; Endometriosis; Laparoscopy; Medroxyprogesterone Acetate; Nandrolone; Pelvic Pain
PubMed: 36995381
DOI: 10.1007/s00404-022-06898-2 -
Annals of Epidemiology Aug 2021To assess the associations between ovarian cancer and depot medroxyprogesterone acetate (DMPA), intrauterine contraceptive devices (IUDs), and partner vasectomy.
PURPOSE
To assess the associations between ovarian cancer and depot medroxyprogesterone acetate (DMPA), intrauterine contraceptive devices (IUDs), and partner vasectomy.
METHODS
We undertook a New Zealand-wide population-based case-control study. During 2013-2015, 205 eligible cases were identified from the cancer registry (152 [74%] participated) and 1,735 eligible controls were randomly selected from the electoral roll (837 [48%] participated). A postal questionnaire was used to gather information.
RESULTS
Ever-use of vasectomy was inversely associated with ovarian cancer in age-adjusted analysis, but not in multivariable analysis (OR = 0.67, 95% CI = 0.46-0.96, and OR = 0.82; 95% CI = 0.54-1.23, respectively). A suggestive trend towards lower risk with longer duration of reliance on partner vasectomy was observed (P-trend = 0.08). Ever-use and duration of use of DMPA were not associated with ovarian cancer. Although ever-use of IUDs was not associated with ovarian cancer, duration of use of IUDs was associated with higher risk (P-trend = 0.04). There were also statistically significant inverse associations between ovarian cancer and use of oral contraceptives, parity, and breastfeeding.
CONCLUSIONS
Prolonged use of IUDs may increase the risk of ovarian cancer. It is also possible that an inverse association exists between ovarian cancer and partner vasectomy.
Topics: Case-Control Studies; Female; Humans; Intrauterine Devices; Male; Medroxyprogesterone Acetate; Ovarian Neoplasms; Pregnancy; Vasectomy
PubMed: 33895242
DOI: 10.1016/j.annepidem.2021.04.006 -
Contraception Apr 2022To describe use of three types of longer-acting contraception-intrauterine devices, subdermal contraceptives, and depot medroxyprogesterone-among transmasculine and...
OBJECTIVE
To describe use of three types of longer-acting contraception-intrauterine devices, subdermal contraceptives, and depot medroxyprogesterone-among transmasculine and cisgender women patients.
STUDY DESIGN
A repeated cross-sectional study using electronic medical records of patients, age 18 to 45, receiving care within Kaiser Permanente Northern California between 2009 and 2019. Variations in demographics, clinical characteristics and contraception method uptake were assessed using t tests for continuous variables and chi-square tests for categorical variables for patients enrolled in 2019. A linear trend test for each group was used to assess the age-adjusted uptake of contraception methods by study year.
RESULTS
The transmasculine group was younger, with a mean age of 27.3 years (±7.2) vs 32.5 years (±7.8) years, respectively p < 0.001. The transmasculine group used more tobacco, alcohol, and illicit drugs. The uptake of these contraception methods increased from 2009 to 2019 for both groups (transmasculine: 0.7% to 4.1%; cisgender: 5.6% to 6.7%) with a positive linear trend for both groups (p = 0.003 and p < 0.001, respectively). The change in uptake of any intrauterine device from 2009 to 2019 was greater for the transmasculine group (0.3% to 2.3% vs 3.3% to 3.5%). Etonogestrel implant uptake had a positive linear trend from 2009 to 2019 for both groups (transmasculine: 0% to 0.5%, p = 0.02, and cisgender 0.1% to 1.2%, p < 0.001).
CONCLUSION
Annual uptake of these contraception methods increased significantly for both transmasculine and cisgender groups, and this increase was greater for the transmasculine patients. Uptake of these contraception methods was higher in the cisgender population.
IMPLICATIONS
These findings suggest an improvement in use of long-term contraception and menstrual suppression medications for the transmasculine population. Further research is needed to understand these differences and identify a possible unmet need for intrauterine and subdermal contraceptives and depot medroxyprogesterone use among this often-marginalized population.
Topics: Adolescent; Adult; Contraception; Contraceptive Agents, Female; Cross-Sectional Studies; Drug Implants; Female; Humans; Intrauterine Devices; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Young Adult
PubMed: 34848179
DOI: 10.1016/j.contraception.2021.11.001 -
Journal of Acquired Immune Deficiency... Oct 2020Depot medroxyprogesterone acetate (DMPA) is a commonly used contraceptive in areas where use of tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure...
BACKGROUND
Depot medroxyprogesterone acetate (DMPA) is a commonly used contraceptive in areas where use of tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis (PrEP) is increasing.
OBJECTIVES
We aimed to investigate the impact of DMPA on PrEP drug pharmacokinetics and pharmacodynamics in women using PrEP before and after DMPA administration.
METHODS
In this pilot study, 12 HIV-negative women ages 18-45 underwent biological sample collection at 3 time points: before study drug, after 2 weeks of daily PrEP use alone, and after 2 weeks of daily PrEP and concomitant DMPA use. We measured drug and drug metabolites in plasma, peripheral blood mononuclear cells, cervicovaginal fluid, cervical tissue, and rectal fluid after each 2-week course of PrEP. We measured HIV replication ex vivo in genital tissue biopsies and innate anti-HIV activity in cervicovaginal fluid before PrEP and after both courses. We compared drug concentrations after PrEP alone to after PrEP and DMPA in the same participant using Wilcoxon signed-rank tests. We used mixed effects linear regression models to compare pharmacodynamic measures for each participant at predrug baseline, after PrEP alone, and after PrEP and DMPA.
RESULTS
We found no significant differences in PrEP drug and drug metabolite concentrations in any compartment during concomitant DMPA use compared with use of PrEP alone, except for a reduction in emtricitabine concentration in cervical tissue. We found no difference in HIV replication in cervical tissue or anti-HIV activity in cervicovaginal fluid during concomitant DMPA and PrEP use compared with during PrEP use alone.
CONCLUSIONS
Concomitant use of DMPA does not clinically alter pharmacokinetics or pharmacodynamics of PrEP in women. These data support the safety of DMPA use in women using PrEP.
Topics: Adolescent; Adult; Anti-HIV Agents; Emtricitabine; Female; HIV Infections; Humans; Leukocytes, Mononuclear; Medroxyprogesterone Acetate; Middle Aged; Pilot Projects; Pre-Exposure Prophylaxis; Tenofovir; Young Adult
PubMed: 32568766
DOI: 10.1097/QAI.0000000000002421