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Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
Journal of Obstetrics and Gynaecology... May 2024To characterise contemporary trends in the hormonal management of endometriosis in adolescent and young adult patients with biopsy-proven endometriosis.
OBJECTIVES
To characterise contemporary trends in the hormonal management of endometriosis in adolescent and young adult patients with biopsy-proven endometriosis.
METHODS
Retrospective chart review of women aged 14-25 years who underwent laparoscopy for pelvic pain with biopsy-proven endometriosis between January 2011 and September 2020 at an academic tertiary hospital system. The final sample included 91 patients with biopsy-confirmed endometriosis.
RESULTS
Combined oral contraceptives (COCs) were the most common initial treatment (64% of patients). Progestin-only formulations (low- and high-dose norethindrone acetate) were offered to younger patients (age 15.9 ± 2.7 years) than those offered COCs (19.9 ± 3.3 years) and levonorgestrel intrauterine devices (LNG-IUDs) (21.9 ± 1.7 years). Current treatments varied widely and included COCs (32%), LNG-IUDs (18%), oral progestins (low- and high-dose norethindrone, medroxyprogesterone) (14%), elagolix (9%), and leuprolide (8%). Oral adjuncts to LNG-IUD were common: usually low- or high-dose norethindrone (37% of patients with an LNG-IUD), but also included progesterone, COCs, and elagolix.
CONCLUSIONS
Oral progestins, LNG-IUDs, and COCs were the mainstay of initial treatment. Subsequent treatments varied widely and included COCs, LNG-IUDs, oral progestins, elagolix, leuprolide, and combinations of these agents. We observed that most young women switched between therapies, suggesting that a personalised approach is often used to determine treatment plans among the wide range of options currently available. This study helps define the spectrum of treatment regimens for endometriosis in adolescent females.
PubMed: 38759792
DOI: 10.1016/j.jogc.2024.102562 -
Preventing Chronic Disease May 2024Haven is a student-run free clinic in New Haven, Connecticut, that serves more than 500 patients annually. Haven's pharmacy department helps patients obtain medications...
INTRODUCTION
Haven is a student-run free clinic in New Haven, Connecticut, that serves more than 500 patients annually. Haven's pharmacy department helps patients obtain medications by providing discount coupons or medications from the clinic's in-house pharmacy, directly paying for medications at local pharmacies, and delivering medications to patients' homes. This study aimed to identify prescriptions that have the highest cost among Haven patients.
METHODS
Our sample consisted of all Haven patients who attended the clinic from March 2021 through March 2023. Patients were eligible to be seen at Haven if they were aged 18 to 65 years, lacked health insurance, and lived in New Haven. We determined the lowest cost of each medication prescribed to Haven patients by comparing prices among local pharmacies after applying a GoodRx discount. We defined expensive medication as more than $20 per prescription. We excluded medical supplies.
RESULTS
Of the 594 Haven patients in our sample, 64% (n = 378) required financial assistance and 22% (n = 129) were prescribed at least 1 expensive medication. Among 129 patients prescribed an expensive medication, the mean (SD) age was 45.0 (12.3) years; 65% were women, and 87% were Hispanic or Latino. Median (IQR) household annual income was $14,400 [$0-$24,000]. We identified 246 expensive medications; the median (IQR) price per prescription was $31.43 ($24.00-$52.02). The most frequently prescribed expensive medications were fluticasone propionate/salmeterol (accounting for 6% of all expensive medications), medroxyprogesterone acetate (6%), albuterol sulfate (5%), and rosuvastatin (5%).
CONCLUSION
The average Haven patient has an income well below the federal poverty level, and many have chronic cardiovascular and respiratory conditions that require expensive medications. Future research should work toward making medications universally affordable.
Topics: Humans; Connecticut; Middle Aged; Female; Male; Adult; Student Run Clinic; Drug Costs; Adolescent; Aged; Young Adult; Prescription Drugs
PubMed: 38753526
DOI: 10.5888/pcd21.230277 -
BMJ (Clinical Research Ed.) May 2024To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial.
OBJECTIVES
To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.
DESIGN
The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial.
SETTING
34 UK hospitals.
PARTICIPANTS
405 women of reproductive age undergoing conservative surgery for endometriosis.
INTERVENTIONS
Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill.
MAIN OUTCOME MEASURES
The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment).
RESULTS
405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00).
CONCLUSIONS
Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some.
TRIAL REGISTRATION
ISRCTN registry ISRCTN97865475.
Topics: Humans; Female; Endometriosis; Contraceptives, Oral, Combined; Adult; Levonorgestrel; Medroxyprogesterone Acetate; Pelvic Pain; Progestins; Pain Measurement; Secondary Prevention; Treatment Outcome; Young Adult; Intrauterine Devices, Medicated
PubMed: 38749550
DOI: 10.1136/bmj-2023-079006 -
European Journal of Clinical... May 2024Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone... (Review)
Review
Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.
BACKGROUND
Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively.
RESULTS
A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG).
CONCLUSIONS
MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.
PubMed: 38726889
DOI: 10.1111/eci.14211 -
PloS One 2024Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and... (Randomized Controlled Trial)
Randomized Controlled Trial
Sexual behaviour among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Data from the ECHO randomized trial.
BACKGROUND
Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments.
METHODS
This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression.
RESULTS
We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively.
CONCLUSIONS
These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well.
Topics: Humans; Female; Levonorgestrel; Medroxyprogesterone Acetate; Intrauterine Devices, Copper; Sexual Behavior; Adult; Young Adult; Contraceptive Agents, Female; Adolescent; Injections, Intramuscular; Contraception; Drug Implants
PubMed: 38722832
DOI: 10.1371/journal.pone.0299802 -
Talanta Aug 2024A film composed of agarose and graphene (G) and magnetic nanoparticles (G-MNPs) is proposed as a sorbent for the extraction and determination of medroxyprogesterone...
A film composed of agarose and graphene (G) and magnetic nanoparticles (G-MNPs) is proposed as a sorbent for the extraction and determination of medroxyprogesterone (MED), levonorgestrel (LEV), norethisterone (NOR) and progesterone (PRO) in natural water samples. Both the preparation of the film and the extraction procedure were optimized. The optimal extraction parameters were as follows: isopropyl alcohol as activation solvent, sample pH value of 3.0, extraction time of 30 min, 1.00 mL of acetonitrile as eluent, elution time of 5 min and sample volume of 100.00 mL. HPLC with photodiode array detector was used for the separation and determination. The method presented a linear range between 2.50 and 75.0 μg L for all analytes, and the LODs were between 1.40 and 1.80 μg L. The method was applied to natural water samples, obtaining satisfactory recovery values (75-111 %). In conclusion, for the immobilization of the G-MNPs, agarose was used, which is a non-toxic, renewable and biodegradable material. The G-MNPs-agarose film was reused up to 70 times, without losing its extraction capacity significantly and presenting excellent sorbent properties, which allow the extraction and preconcentration of the progestogens under study.
Topics: Water Pollutants, Chemical; Progestins; Adsorption; Magnetite Nanoparticles; Solid Phase Extraction; Sepharose; Chromatography, High Pressure Liquid
PubMed: 38718645
DOI: 10.1016/j.talanta.2024.126189 -
Frontiers in Endocrinology 2024For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and...
Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.
BACKGROUND
For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs.
METHODS
This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m) and high BMI (≥24 kg/m) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes.
RESULTS
For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, = 0.031).
CONCLUSIONS
For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.
Topics: Humans; Female; Pregnancy; Ovulation Induction; Body Mass Index; Adult; Retrospective Studies; Medroxyprogesterone Acetate; Pregnancy Outcome; Pregnancy Rate; Progestins; Fertilization in Vitro; Dose-Response Relationship, Drug
PubMed: 38699386
DOI: 10.3389/fendo.2024.1352522 -
JAMA May 2024Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects... (Review)
Review
IMPORTANCE
Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years.
OBSERVATIONS
The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up.
CONCLUSIONS AND RELEVANCE
For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.
Topics: Aged; Female; Humans; Middle Aged; Breast Neoplasms; Calcium; Calcium, Dietary; Cardiovascular Diseases; Diet, Fat-Restricted; Dietary Supplements; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Hot Flashes; Medroxyprogesterone Acetate; Osteoporosis, Postmenopausal; Postmenopause; Randomized Controlled Trials as Topic; Vitamin D; Women's Health; United States
PubMed: 38691368
DOI: 10.1001/jama.2024.6542 -
Pharmaceutics Apr 2024Long-acting injectable (LAI) formulations provide sustained drug release over an extended period ranging from weeks to several months to improve efficacy, safety, and...
Long-acting injectable (LAI) formulations provide sustained drug release over an extended period ranging from weeks to several months to improve efficacy, safety, and compliance. Nevertheless, many challenges arise in the development and regulatory assessment of LAI drug products due to a limited understanding of the tissue response to injected particles (e.g., inflammation) impacting in vivo performance. Mechanism-based in silico methods may support the understanding of LAI-physiology interactions. The objectives of this study were as follows: (1) to use a mechanistic modeling approach to delineate the in vivo performance of DepoSubQ Provera and formulation variants in preclinical species; (2) to predict human exposure based on the knowledge gained from the animal model. The PBPK model evaluated different elements involved in LAI administration and showed that (1) the effective in vivo particle size is potentially larger than the measured in vitro particle size, which could be due to particle aggregation at the injection site, and (2) local inflammation is a key process at the injection site that results in a transient increase in depot volume. This work highlights how a mechanistic modeling approach can identify critical physiological events and product attributes that may affect the in vivo performance of LAIs.
PubMed: 38675213
DOI: 10.3390/pharmaceutics16040552