-
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 -
Acta Psychologica Jul 2024Increasing research has focused on how ovarian hormones influence individual prosocial motivation and cooperation. However, most results remain ambiguous and...
Increasing research has focused on how ovarian hormones influence individual prosocial motivation and cooperation. However, most results remain ambiguous and contradictory. Here, we collected progesterone (PROG) and oestradiol from 62 healthy women with regular menstrual cycles to explore whether variations in ovarian hormones could flexibly change their cooperative preference according to their opponents' strategies in multiple rounds of a prisoner's dilemma (PD) game. Participants in different menstrual phases (32 in the follicular phase [FP] and 30 in the luteal phase [LP]) were asked to complete 20 rounds of PD games with each of three computer opponents holding different cooperative strategies. The results revealed that in PD games that did not require cooperation for increased outcomes, women in the LP (high PROG) reduced their cooperation rate more significantly than women in the FP (low PROG). In contrast, when the game design required reciprocity, simultaneously elevated levels of PROG and oestradiol predicted greater instances of participants choosing to cooperate. Furthermore, we found that elevated PROG levels accounted for women's elevated prosocial choices, regardless of the need to increase outcomes through cooperation. These results implied higher levels of PROG and oestradiol influence women's cooperative strategies resulting in increased social interactions.
Topics: Humans; Female; Progesterone; Estradiol; Prisoner Dilemma; Adult; Cooperative Behavior; Young Adult; Interpersonal Relations
PubMed: 38759584
DOI: 10.1016/j.actpsy.2024.104307 -
Stroke Jul 2024The commonly used combined hormonal contraceptives with progestins and ethinylestradiol are associated with an increased risk of ischemic stroke (IS). Progestin-only...
BACKGROUND
The commonly used combined hormonal contraceptives with progestins and ethinylestradiol are associated with an increased risk of ischemic stroke (IS). Progestin-only preparations, including levonorgestrel-releasing intrauterine devices (LG-IUDs), are not associated with an increased risk, and in smaller studies, the risk is even reduced. The risk of intracerebral hemorrhage (ICH) has never been investigated. We studied the risk of IS and ICH in women using LG-IUDs compared with women not using hormonal contraceptives.
METHODS
In this Danish historical cohort study (2004-2021), we followed nonpregnant women (18-49 years) registering incident IS and ICH in relation to use of LG-IUDs/nonuse of hormonal contraceptives utilizing Danish high-quality registries with nationwide coverage. Poisson regression models adjusting for age, ethnicity, education, calendar year, and medication use for risk factors were applied.
RESULTS
A total of 1 681 611 nonpregnant women contributed 11 971 745 person-years (py) of observation. Mean age at inclusion was 30.0 years; mean length of follow-up was 7.1 years; 2916 women (24.4 per 100 000 py) had IS; 367 (3.1 per 100 000 py) had ICH. Of these, 364 784 were users of LG-IUD contributing 1 720 311 py to the investigation; mean age at start of usage was 34.6 years. Nonusers of hormonal contraceptives contributed 10 251 434 py; mean age at inclusion was 30.0 years. The incidence rate of IS/ICH among LG-IUD users was 19.2/3.0 and among nonusers, it was 25.2/3.1 per 100 000 py. After adjustment, incidence rate ratio for IS was 0.78 (CI, 0.70-0.88), and for ICH it was 0.94 (CI, 0.69-1.28).
CONCLUSIONS
The use of LG-IUD was associated with a 22% lower incidence rate of IS without raising the incidence rate of ICH. The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent IS.
Topics: Humans; Female; Adult; Levonorgestrel; Intrauterine Devices, Medicated; Middle Aged; Adolescent; Young Adult; Denmark; Stroke; Cohort Studies; Risk Factors; Incidence; Contraceptive Agents, Female; Cerebral Hemorrhage; Contraception; Ischemic Stroke
PubMed: 38753961
DOI: 10.1161/STROKEAHA.124.047438 -
Scientific Reports May 2024A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant...
A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.
Topics: Humans; Female; Pregnancy; Adult; Pregnancy, Ectopic; Biomarkers; Prospective Studies; Pregnancy Trimester, First; Machine Learning; Abortion, Spontaneous; Pregnancy Outcome; Progesterone; Chorionic Gonadotropin, beta Subunit, Human
PubMed: 38750192
DOI: 10.1038/s41598-024-61690-3 -
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 -
Gynecological Endocrinology : the... May 2024Progestin-primed ovarian stimulation (PPOS) is an efficient controlled ovarian stimulation (COS) method. The study explored the pregnancy outcomes between PPOS and... (Comparative Study)
Comparative Study
OBJECTIVES
Progestin-primed ovarian stimulation (PPOS) is an efficient controlled ovarian stimulation (COS) method. The study explored the pregnancy outcomes between PPOS and antagonist ovarian stimulation protocol (GnRH-ant) in infertile patients with poor ovarian response (POR).
METHODS
This retrospective study included patients with POR who underwent COS at the Reproductive Medical Center of Shanxi Maternal and Child Health Hospital from January 2021 to April 2022. The cycles were grouped as the GnRH-ant group and the PPOS group. The primary outcome was the clinical pregnancy rate; the secondary outcomes included the biochemical pregnancy abortion rate and live birth rate.
RESULTS
Frozen embryo transfer was used in all cycles in this study. The cycles were divided into the GnRH-ant ( = 236 cycles) and PPOS ( = 273 cycles) groups. Age, BMI, type of infertility, infertility duration, FSH, LH, PRL, E2, T, P, and the number of cycles in the hospital were similar between the two groups (all > 0.05). No statistically significant differences were observed in the clinical pregnancy rate (primary outcome, 32.71% vs. 43.90%, = 0.082), total Gn dose, total Gn days, ART mode (IVF or ICSI), AFC, MII follicles, 2PN embryos, fertility, cycle cancelation rate, biochemical pregnancy rate, abortion rate, or live birth rate between the two groups (all > 0.05). The PPOS group exhibited a higher rate of high-quality embryos than the GnRH-ant group (50.12% vs. 42.90%, = 0.045).
CONCLUSIONS
The PPOS protocol was comparable to the GnRH-ant protocol regarding induction parameters and cycle cancelation, biochemical pregnancy, clinical pregnancy, and abortion rates but might be associated with a higher proportion of high-quality embryos.
Topics: Humans; Female; Pregnancy; Ovulation Induction; Retrospective Studies; Adult; Progestins; Pregnancy Outcome; Gonadotropin-Releasing Hormone; Pregnancy Rate; Infertility, Female; Embryo Transfer; Hormone Antagonists
PubMed: 38749017
DOI: 10.1080/09513590.2024.2352133 -
Scientific Reports May 2024To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women...
To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women who intended to use the ENG implant. Exclusion criteria included abnormal uterine bleeding, inability to attend a 1-year follow-up, and implant removal for reasons unrelated to vaginal bleeding or loss of follow-up. We obtained endometrial biopsies before implant placement and assessed the expression of 20 selected genes. Users maintained a uterine bleeding diary for 12 months post-implant placement. For statistical analysis, we categorized women into those with or without favorable vaginal bleeding at 3 and 12 months. Women with lower CXCL1 expression had a 6.8-fold increased risk of unfavorable vaginal bleeding at 3 months (OR 6.8, 95% CI 2.21-20.79, p < 0.001), while those with higher BCL6 and BMP6 expression had 6- and 5.1-fold increased risks, respectively. By the 12-month follow-up, women with lower CXCL1 expression had a 5.37-fold increased risk of unfavorable vaginal bleeding (OR 5.37, 95% CI 1.63-17.73, p = 0.006). Women with CXCL1 expression < 0.0675, BCL6 > 0.65, and BMP6 > 3.4 had a higher likelihood of experiencing unfavorable vaginal bleeding at 3 months, and CXCL1 < 0.158 at 12 months. Users of ENG contraceptive implants with elevated BCL6 and BMP6 expression exhibited a higher risk of breakthrough bleeding at the 3-month follow-up. Conversely, reduced CXCL1 expression was associated with an elevated risk of bleeding at both the 3 and 12-month follow-ups.
Topics: Humans; Female; Desogestrel; Adult; Prospective Studies; Uterine Hemorrhage; Contraceptive Agents, Female; Endometrium; Drug Implants; Chemokine CXCL1; Young Adult
PubMed: 38745005
DOI: 10.1038/s41598-024-61751-7 -
Women's Health (London, England) 2024Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be...
BACKGROUND
Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy.
OBJECTIVE
To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery.
DESIGN
Prospective non-interventional cohort study.
METHODS
We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient's assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm).
RESULTS
We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p < 0.01), while a significant reduction was registered in the dienogest (35.1 versus 25.8; p < 0.01) and estrogen-progestogens (28.4 versus 16.7; p < 0.01) groups; no significant difference in ovarian endometrioma diameter reduction between these two latter groups was noted (p = 0.18). Ovarian endometrioma-associated symptoms and pain improved in dienogest and estrogen-progestogens groups, with a significantly greater effect for dienogest than for estrogen-progestogens for dysmenorrhea (74% versus 59%; p < 0.01). In the sub-group of women eligible for first-line surgery at baseline, long-term treatment with dienogest and estrogen-progestogens reduced surgical eligibility by 30%.
CONCLUSIONS
Decreased mean largest ovarian endometriomas'diameter after 12 months and reduction of the need for surgical treatment by 30% were observed in dienogest and estrogen-progestogens groups. Long-term treatment with dienogest had a greater effect in alleviating dysmenorrhea and pain.
Topics: Humans; Female; Nandrolone; Endometriosis; Adult; Prospective Studies; Ovarian Diseases; Progestins; Estrogens; Treatment Outcome; Young Adult
PubMed: 38738634
DOI: 10.1177/17455057241252573