Progestogen-only Research Articles

S750 Risk of Constipation and Slow Transit Constipation in Pre- and Peri-Menopause, Non-Obese Women on Progestogen-Only Contraceptives Versus Combined OCP: A Multi-Center Analysis

S750 Risk of Constipation and Slow Transit Constipation in Pre- and Peri-Menopause, Non-Obese Women on Progestogen-Only Contraceptives Versus Combined OCP: A Multi-Center Analysis

Understanding and Offering Counseling to Your Patients about the First Over the Counter Progestin-Only Oral Contraceptive (OPill®).

Understanding and Offering Counseling to Your Patients about the First Over the Counter Progestin-Only Oral Contraceptive (OPill®).

Treatments of unscheduled vaginal bleeding due to progestin-only contraception.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness, safety, and side effects associated with the usage of different treatments for unscheduled vaginal bleeding in premenopausal women using progestin-only pills.

WITHDRAWN: Comparing English- and Spanish-Reading Patients’ Comprehension of the Drug Facts Label for a New Over-The-Counter Oral Contraceptive

BackgroundHealth literacy is known to impact health outcomes in a multitude of ways and is impacted by language barriers. Lower health literacy is also associated with higher rates of unintended pregnancies. A progestin-only oral hormonal contraception product, norgestrel (Opill-Perrigo), was approved for over-the-counter (OTC) use in the United States in July 2023. Objective(s): The objective was to utilize a knowledge assessment survey to determine participants’ comprehension of norgestrel from its drug facts label and compare the comprehension between primarily English- and Spanish-reading participants. MethodsA 7-item knowledge assessment was developed and distributed to English and Spanish readers at one site within a network of federally qualified health centers. English-reading participants completed the English survey alongside use of an English copy of norgestrel’s drug facts label. Spanish-reading participants completed the Spanish survey and were randomized in a 1:1 fashion to either receive an English or Spanish copy of norgestrel’s drug facts label. ResultsThe English-reading/English label (E/E) group had a higher level of comprehension of norgestrel’s drug facts label compared to the Spanish-reading/English label (S/E) or Spanish-reading/Spanish label (S/S) groups. ConclusionDifferences exist in OTC label comprehension for norgestrel based on primary language able to be read. Advocacy for OTC labels to be readily available in languages other than English is imperative to mitigate unintended pregnancies associated with lower levels of health literacy.

O-011 Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Efficacy of natural progesterone

Abstract Study question Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Summary answer Inhibition of the LH surge by progesterone during the luteal phase of duostim protocols in POR appears to be effective, safe and makes GnRH-antagonists unnecessary. What is known already High levels of progesterone have long been shown to reversibly block the LH surge associated with increased estradiol levels, by reducing GnRH’s pulsatility from the hypothalamus. This inhibition is the basis of progestin-only contraceptives and has been shown to be completely reversible by discontinuing the progestin, and even seems to have a potentiating effect on the surge which occurs in the subsequent few days Study design, size, duration This is a secondary analysis of the BISTIM study, a multicentre, open-labelled randomized controlled trial, performed in 4 french IVF centers from 2018 to 2021, designed to compare Duostim protocol versus two follicular stimulations. We here present a paired-controlled study including patients randomized in the Duostim group, who underwent 2 consecutive stimulations in the same menstrual cycle, we compare the follicular phase stimulation with GnRH-antagonist versus the luteal phase stimulation with progesterone. Participants/materials, setting, methods The BISTIM study recruited poor ovarian reserve women defined with Bologna criteria who enrolled in an IVF or ICSI program, aged from 20 to 41, with BMI from 19 to 32, with no more than 2 previous IVF cycles. Women with amenorrhea, FSH >20 UI/L or CFA <1 were not included. 32 of them underwent two stimulations, consecutively. Main results and the role of chance For the same group of 32 women, stimulation parameters were similar between 1st and 2nd stimulations (stimulation duration, gonadotropin doses, number of retrieved oocytes). As expected, progesterone levels were significantly higher at D5 in the study group compared to controls (mean 34.8 ng/ml, Q1-Q3 [18.4 – 51.6])) and were still significantly higher at HCG-day (10.7 ng/ml, Q1-Q3 [2.7 – 14.3])), despite the addition of natural exogenous progesterone. LH levels were significantly lower in the progesterone group, regardless of the day of stimulation: at HCG day mean LH was 1,7 UI/L in the study group versus 6.8 UI/L in the control group, p < 0.001. In the Duostim group no premature LH surge/ovulation was observed, however, 2 cancellations for premature ovulation were reported with antagonist protocol in the control group of the BISTIM study. Limitations, reasons for caution This study was carried out on a limited number of subjects (n = 32), all of whom were poor responders. Wider implications of the findings This study shows the effectiveness of LH surge inhibition by progestins, which represent a less expensive and more patient-friendly treatment than traditional protocols. Further studies are needed to determine the best protocol (type and doses of progestins) to effectively inhibit the LH surge, and on larger and different cohorts. Trial registration number 2017-A00498-45

The prevalence of contraceptive use among postpartum women and its associated factors during the early phase of COVID-19 outbreak: a time series study

BackgroundUnintended pregnancies can adversely affect maternal health, preventable through timely postpartum contraception. During the COVID-19 pandemic, family planning services were constrained by policies that curtailed outpatient visits. We investigated the prevalence of postpartum contraceptive initiation at King Chulalongkorn Memorial Hospital (KCMH) during January to June 2020, comparing with the same period in 2019, and identified factors associated with such initiation.MethodsWe reviewed the medical records of 4506 postpartum women who delivered at KCMH during the study period. Logistic regression was conducted to test the association between early COVID-19 phase deliveries and post-partum long acting reversible contraception (LARC) initiation including copper intrauterine devices, levonorgestrel intrauterine systems, contraceptive implants, and progestogen-only injectable contraceptives.ResultsA total of 3765 women (83.6%), of whom 1821 delivered during the pandemic and 1944 during the historical cohort period, were included in this study. The proportion of women who initiated non-permanent modern contraceptives at six weeks postpartum was comparable between the COVID-19 (73.4%) and historical cohort (75.3%) (p = 0.27) periods. The proportion of women who initiated LARC at six weeks postpartumwas comparable between the historical cohort period (22.5%) and the COVID-19 (19.7%) (p = 0.05) period. Accessing a six-week postpartum check-up was independently associated with LARC initiation, of which the adjusted odds ratio (OR) (95% confidence interval) was 3.01 (2.26 to 4.02).ConclusionsOur findings demonstrated that accessing postpartum care significantly associate with the use of LARC. The data suggest the strong influence of postpartum check-ups in facilitating the adoption of effective contraception, emphasizing the need for accessible postpartum care to sustain maternal health during health crises.

Hysteroscopic evaluation of endometrial changes and fallopian tubal functions in women using progestin-only contraceptives

The purpose of this prospective study was to investigate whether office hysteroscopy (OH) can be used to assess the mechanisms of action of progestogen-only contraceptives (POCs), diagnose possible local causes of abnormal uterine bleeding (AUB), and support the treatment plan of symptomatic patients using POCs compared with those who do not use hormones. The study included 140 women who were divided into two groups. Group A consisted of 70 women who used POCs, whereas group B consisted of 70 women who did not use hormones. They were successively examined using transvaginal ultrasonography (TVS), OH, and endometrial sampling. The TVS results were consistent with those of OH and histopathology. The changes in endometrial thickness and vasculature, as well as fallopian tube (FT) functions, were significantly more pronounced in POC users than in non-POC users. There was a significant reduction in the peristalsis of the proximal part of the FT, as well as a reduction in the bubble flow test in group A compared with group B. In addition, the combination of peristalsis and the bubble flow test (Darwishscope test) was significantly lower in group A. It was concluded that using OH as a simple diagnostic tool in women with POCs would contribute to a better understanding of the mechanisms of endometrial and FT effects and explain some local endometrial causes of AUB. This ensures that the combination of TVS and OH would limit routine endometrial sampling in POCs users.

Abstract PS10-01: Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Pathogenic Variants in BRCA1 and BRCA2

Abstract BACKGROUND: Current use of hormonal contraception is associated with a 20-30% relative increase in the risk of breast cancer (BC) for women in the general population compared with never using. Longer duration of use is associated with higher risk, and the risk remains elevated above that of never users for at least 5 years after cessation. Most published data are for various formulations of the combined oral contraceptive pill, but associations are similar for progestogen-only contraceptives, including intrauterine devices. For women in the general population who use hormonal contraceptives in their 20s and 30s, when baseline BC risk for most women is low, these increased relative risks translate into only small increases in absolute risk. It is unclear whether use of hormonal contraceptives increases BC risk for women carrying a germline BRCA1 or BRCA2 pathogenic variant (PV). These women are at markedly higher risk of early-onset BC, so even slightly increased relative risks could translate to important increases in their absolute risk of BC. This study assessed the association between use of any hormonal contraception and BC risk for BRCA1 and BRCA2 PV carriers using individual participant data from four prospective cohorts. METHODS: Data from females born after 1920 with a PV in BRCA1 or BRCA2 and no history of cancer or bilateral mastectomy at cohort entry were analyzed. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BC (invasive disease or ductal carcinoma in situ) associated with use of hormonal contraceptives for at least 1 year, with age as the timescale, entry at cohort enrolment, and censoring at the earlier of bilateral mastectomy, death, diagnosis of another cancer or last follow-up. Analyses were adjusted for study, birth cohort, first-degree family history of BC, parity, premenopausal bilateral oophorectomy and menopausal status. Current use of hormonal contraceptives was defined as use within the previous year, to account for cessation of use due to BC symptoms or clinical investigation. RESULTS: Of 3,882 BRCA1 and 1,509 BRCA2 PV carriers, 53% and 71%, respectively had ever used hormonal contraceptives (for at least one year). The median cumulative duration of hormonal contraceptive use was 4.8 and 5.7 years, respectively. Overall, 488 BRCA1 and 191 BRCA2 PV carriers developed incident BC during a median of 5.9 and 5.6 years of follow-up, respectively. For BRCA1 PV carriers, use of hormonal contraceptives for at least 1 year was associated with increased BC risk (HR [95% CI]: 1.29 [1.04-1.60] p=0.019). BC risk increased with longer cumulative duration of hormonal contraceptive use (HR [95% CI]: 1.13 [0.88-1.45] p=0.35, 1.48 [1.11-1.96] p=0.007 and 1.56 [1.13-2.17] p=0.007 for 1-5, 6-10 and >10 years of use, respectively), with an estimated proportional increase in risk of 3% (1%-5%, p=0.002) for each additional year of use. For BRCA2 PV carriers, there was no evidence that current or past use, or cumulative duration of use, were associated with increased risk of BC, but confidence intervals on the HRs were wide. CONCLUSION: Hormonal contraceptive use is associated with an increased risk of BC for women carrying PVs in BRCA1 and risk increases with cumulative duration of use. Hormonal contraceptives are an important healthcare option for women; they provide excellent contraceptive efficacy and reduce risks of ovarian and endometrial cancer. Decisions about use of hormonal contraceptives in women at increased risk for BC due to BRCA1 PVs need to carefully weigh the risks and benefits; while shorter-term use may result in only small increases, prolonged cumulative use may result in larger increases in absolute BC risk that may not be acceptable to some women. Citation Format: Kelly-Anne Phillips, Joanne Kotsopoulos, Susan Domchek, James Chamberlain, Julie Bassett, Amber Aeilts, Irene Andrulis, Saundra Buys, Wanda Cui, Mary Daly, Andrea Eisen, William Foulkes, Michael Friedlander, Jacek Gronwald, John Hopper, Esther John, Beth Karlan, Raymond Kim, Jan Lubiński, Kelly Metcalfe, Katherine Nathanson, Christian F. Singer, Heather Symecko, Nadine Tung, Steven Narod, Mary Beth Terry, Roger Milne. Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Pathogenic Variants in BRCA1 and BRCA2 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-01.

Progestogen only contraception in women with congenital heart disease

Background There is little information of progestogen-only contraceptives in patients with congenital heart disease (CHD) on the long-term. Objective To evaluate the use of contraception in patients with CHD. We studied both short-acting reversible contraceptives (SARCs), oral progestin-only pills (POPs) and long-acting reversible contraceptives (LARCs): intrauterine devices (IUD-IPs) and subdermal implants both impregnated with progestogens (SI-IPs). Study design Retrospective study of all women attending the preconception clinic. Contraceptive methods were classified in three TIERs of effectiveness before and after consultation. ESC classification regarding pregnancy risk, WHOMEC classification for combined oral contraceptive safety was collected. Results Six hundred and fifty-three patients. A significant proportion of them switched from TIER 3 to TIER 2 or 1 (p < .001) after consultation. One hundred and ninety-nine patients used POPs, 53 underwent IUD-IPs implantation and 36 SI-IPs, mean duration was 58 ± 8, 59 ± 8 and 53 ± 38 months, respectively. Conclusions Because of their safety and efficacy, IUD-IPs and SI-IPs should be considered as first-line contraception in patients with CHD.

Relationship between long-acting reversible contraception and acne in a cohort of adolescents and young adults.

The use of progestin-only long-acting reversible contraception (LARC) may be a risk factor for acne. Few studies have focused primarily on the effects of hormonal LARC on the development or exacerbation of acne in adolescents and young adults. We sought to understand the incidence and management of acne following hormonal LARC insertion in this adolescent/young adult population. A secondary data analysis was conducted of prospectively collected quality improvement (QI) data from the Adolescent Medicine LARC Collaborative. Subjects were evaluated by clinicians in adolescent medicine clinics at participating study sites, and acne severity was documented using a standardized recording instrument and scale. Descriptive statistics were reported as frequencies and percentages for categorical variables or mean and standard deviation (SD) for continuous variables. We compared demographic and clinical characteristics by those who had worsening acne, accounting for site inter-correlation using Cochran-Mantel-Haenszel chi-square tests for categorical variables and linear generalized estimating equation (GEE) regression for continuous variables. Of 1319 subjects who completed LARC insertion, 28.5% (376/1319) experienced worsening acne following use of progestin-only LARC. Acne was a contributing factor to LARC removal in only 3% (40/1319), and the sole reason for removal in 0.4% (5/1319) of all subjects. As this was a secondary analysis of prospectively collected QI data, limitations of this study include incomplete or inaccurate documentation of acne severity. Moreover, LARC insertions without follow-up/removal visits or with only follow-up/removal within 8 weeks of insertion were excluded from our study, which may also bias results. Adolescents and young adults seeking progestin-only LARC should be counseled about the potential for developing acne or experiencing a worsening of existing acne during LARC use. However, acne was not a common reason for LARC discontinuation.

Preferências contraceptivas entre mulheres com doença falciforme durante um acompanhamento de 12 meses: um estudo longitudinal

Abstract Objectives: to analyze the choice and continuation rate of contraceptive methods in women with sickle cell disease (SCD). Methods: an exploratory prospective study was conducted at a hospital enrolling 44 women with SCD aged 15-40 years old. After contraceptive counseling, the women selected one of the available contraceptive methods and separated into two groups, and were followed up at one, three, six, and 12 months. To analyze the continuation rate of contraceptive use, the two groups were: group (G1) using progestin-only contraceptives, through any route of administration and group (G2) using other contraceptive methods (combined hormonal and non-hormonal contraceptives). The continuation rate was analyzed using Kaplan–Meier survival analysis, considering a p&lt;0.05. Results: after contraceptive counseling, most women opted for any progestin-only methods: injectable contraceptives (n=18; 40.9%), oral contraceptives (n=7; 15.9%), or intrauterine devices (n=3; 6.8%). The continuation rate decreased in both groups during the 12-months follow-up period. In the G1, the continuation rate was 60.7% (CI95%=40.4-76.0), while that in the G2 was 68.7% (CI95%= 40.5-85.6) with no significant difference between the groups (p=0.641). Conclusions: the overall continuation rates in both groups were satisfactory. No significant difference in the continuation rate of contraceptive methods was observed between the groups, although most women preferred progestin-only methods.

The injectable contraceptives depot medroxyprogesterone acetate and norethisterone enanthate substantially and differentially decrease testosterone and sex hormone binding globulin levels: A secondary study from the WHICH randomized clinical trial.

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018-2019, randomized HIV-negative women aged 18-40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214-218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).

Hormonal Contraceptive Use Is Associated With a Decreased Incidence of Hypothyroidism

ObjectiveHypothyroidism is one of the most common endocrine disorders affecting 5 to 10 times more women than men. Given this higher incidence in women, it is possible that hormonal differences or medications more commonly used by women may play a role in the risk of developing hypothyroidism. We hypothesized that hormonal contraception affects the risk of developing hypothyroidism. MethodsUsing the TriNetX database, we developed a case-control study and identified women aged 18 to 45 years in 4 distinct groups: (1) estrogen-progestin contraceptive (EPC) use, (2) progestin-only contraceptive (POC) use, (3) progestin-containing intrauterine device (IUD) use, and (4) controls. For each group, we ascertained data including the diagnosis of hypothyroidism, alcohol use, tobacco use, and body mass index. ResultsWe identified 18 578 patients with sufficient data: EPC use, n = 5849; POC use, n = 5052; IUD use, n = 1000; and controls, n = 6677. A total of 118 individuals (1.8%) in the control group and 165 individuals (1.4%) who received hormonal contraception developed hypothyroidism. After using a logistic model to account for cofounding variables, all forms of hormonal contraception (EPC, POC, and IUD) had a protective effect against the diagnosis of hypothyroidism. POC and IUD uses had the greatest protective effect, with odds ratios of 0.14 and 0.12, respectively. EPC had a less pronounced but still significant effect, with an odds ratio of 0.30 (P < .001). ConclusionThis study of >18 000 women and the risk of developing hypothyroidism demonstrates a protective effect of hormonal contraceptive use. Our data, both unadjusted and adjusted using a logistic model to account for cofounding variables, suggest that the use of hormonal contraception, in any form, decreases the risk of developing hypothyroidism.

Contraceptive effects on the cervicovaginal microbiome: Recent evidence including randomized trials.

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. This narrative review summarises recent evidence of the effect of contraceptives on the cervicovaginal microbiome, emphasising data obtained through randomized trials. 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. 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.

Preconception contraceptive use and miscarriage: prospective cohort study

ObjectivesTo evaluate the association between preconception contraceptive use and miscarriage.DesignProspective cohort study.SettingResidents of the United States of America or Canada, recruited from 2013 until the end of 2022.Participants13 460 female...

Comparison of thromboembolism outcomes in patients with sickle cell disease prescribed hormonal contraception

AbstractPatients with sickle cell disease (SCD) are at a risk of thromboembolism (TE), and use of hormonal contraception can further increase that risk. This study aims to assess patterns of hormonal contraceptive use and compare risk of contraception-related TE between combined hormonal contraceptives (CHCs) and progestin-only contraceptives (POCs). Patients with SCD aged between 12 and 44 years with a new prescription of a hormonal contraceptive in the Centers for Medicare and Medicaid Services Medicaid Analytic eXtract database (2006-2018) were followed up to 1 year. We identified 7173 new users: 44.6% initiated CHC and 55.4% initiated POC. Combined oral contraceptive pills (OCPs; 36.5%) and progestin-only depot medroxyprogesterone acetate (33.9%) were the most frequently prescribed agents. A total of 1.8% of contraception users had a new diagnosis of TE within 1 year of the first identified contraception prescription. There were no significant differences in TE event rates between CHC and POC users (17.2 and 24.7 events per 1000 person-years, respectively). In patients prescribed OCP, there were no differences in TE event rates based on estrogen dose or progestin generation. Transdermal patch had a 2.4-fold increased risk of TE as compared with that of OCP. Although limited by the retrospective study design and use of administrative claims data, this study found no significant differences in TE rates between new users of CHC and POC in patients with SCD. Careful evaluation of underlying TE risk factors should be considered for each patient with SCD before initiation of hormonal contraception.

Drug-induced liver injury secondary to increased levonorgestrel exposure in a patient taking ritonavir.

We report the first published case of a drug induced liver injury (DILI) presumed secondary to a drug-drug interaction between ritonavir and levonorgestrel progestogen-only emergency contraception (POEC). Our patient is a 25-year-old female living with human immunodeficiency virus (HIV), taking antiretroviral therapy (ART) containing tenofovir alafenamide/emtricitabine and darunavir/ritonavir. She was found to have elevated transaminases at a routine clinic appointment consistent with hepatocellular DILI. Further investigation found the most likely cause of this was a drug-drug interaction (DDI) between the ritonavir component of her ART and recent use of levonorgestrel POEC 3days earlier. Evidence suggests that ritonavir increases levonorgestrel exposure, yet our patient received double the usual dose as per dispensing guidance at the time. We review the pharmacokinetics of ritonavir-levonorgestrel DDIs and highlight the need for consistent guidelines on this topic.

Current approaches in managing pregnancy in kidney transplant recipients

End-stage renal disease impacts fertility, causing functional menopause in female patients. Within 3 months of successful renal transplant, menstrual function normalizes, ovulation recommences due to improved hypothalamic–pituitary–ovarian axis function, and, thereby, fertility is restored in 80–90% of women in the childbearing age group. In such circumstances, any unplanned pregnancy poses a significant risk to the mother and the child, and the allograft. Pregnancy, in general, does not negatively impact long-term allograft function or survival if the baseline function of the allograft is excellent. Risk predictors of clinical adverse outcomes and graft loss during pregnancy include short transplant–pregnancy interval, preconception graft function, hypertension, preconception proteinuria, and preeclampsia. The recommended and safer maintenance immunosuppressive regimen during pregnancy is calcineurin inhibitors (CNI) (tacrolimus/cyclosporine), azathioprine, and steroids. Sirolimus/everolimus and mycophenolate mofetil should be withdrawn 6 weeks before planned conception. To avoid acute rejections, drug levels should be monitored closely, and the dosage should be modified to reach the recommended target level. Addressing contraception must be a crucial component of the pretransplant counseling process to prevent premature unplanned pregnancies. Mechanical contraceptives are safe for transplant recipients, convenient, and easy to use, with no concerns regarding interaction with immune suppressants; nevertheless, their efficacy depends on user compliance which is difficult to achieve in most cases. However, combined oral contraceptives and progestin-only contraceptives have an inhibitory effect on P 450 3A4, thus increasing the concentration of CNIs particularly cyclosporine. Furthermore, CNIs, in particular, tacrolimus, have an inductive effect on P 450 3A4, potentially reducing the contraceptive efficacy. Therefore, successful pregnancy depends on thorough prepregnancy counseling, careful family planning, and multidisciplinary teamwork. Breastfeeding is not contraindicated and should not be discouraged.

Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation.

Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that ZBTB16 levels are induced by medroxyprogesterone acetate (MPA) and etonogestrel (ETO) in cultured HESCs. We hypothesized that pLARC-induced ZBTB16 expression contributes to HESC decidualization, whereas prolonged enhancement of ZBTB16 levels triggers an inflammatory milieu by inducing pro-inflammatory gene expression and tissue-factor-mediated thrombin generation in decidualized HESCs. Thus, ZBTB16 immunostaining was performed in paired endometria from pre- and post-depo-MPA (DMPA)-administrated women and oophorectomized guinea pigs exposed to the vehicle, estradiol (E2), MPA, or E2 + MPA. The effect of progestins including MPA, ETO, and levonorgestrel (LNG) and estradiol + MPA + cyclic-AMP (E2 + MPA + cAMP) on ZBTB16 levels were measured in HESC cultures by qPCR and immunoblotting. The regulation of ZBTB16 levels by MPA was evaluated in glucocorticoid-receptor-silenced HESC cultures. ZBTB16 was overexpressed in cultured HESCs for 72 h followed by a ± 1 IU/mL thrombin treatment for 6 h. DMPA administration in women and MPA treatment in guinea pigs enhanced ZBTB16 immunostaining in endometrial stromal and glandular epithelial cells. The in vitro findings indicated that: (1) ZBTB16 levels were significantly elevated by all progestin treatments; (2) MPA exerted the greatest effect on ZBTB16 levels; (3) MPA-induced ZBTB16 expression was inhibited in glucocorticoid-receptor-silenced HESCs. Moreover, ZBTB16 overexpression in HESCs significantly enhanced prolactin (PRL), insulin-like growth factor binding protein 1 (IGFBP1), and tissue factor (F3) levels. Thrombin-induced interleukin 8 (IL-8) and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in control-vector-transfected HESCs were further increased by ZBTB16 overexpression. In conclusion, these results supported that ZBTB16 is enhanced during decidualization, and long-term induction of ZBTB16 expression by pLARCs contributes to thrombin generation through enhancing tissue factor expression and inflammation by enhancing IL-8 and PTGS2 levels in decidualized HESCs.

The most common medications dispensed to lactating persons: An electronic health record-based approach.

Using a novel, electronic health record (EHR)-based approach, to estimate the prevalence of prescription medication use at 2, 4, and 6 months postpartum among lactating individuals. We utilized automated EHR data from a US health system that records infant feeding information at well-child visits. We linked mothers who received prenatal care to their infants born May 2018-June 2019, and we required infants to have ≥1 well-child visit between 31 and 90 days of life (i.e., 2-month well-child visit with a ±1 month window). Mothers were classified as lactating at the 2-month well-child visit if their infant received breast milk at the 2-month well-child visit. For subsequent well-child visits at 4 and 6 months, mothers were considered lactating if their infant was still receiving breast milk. We identified 6013 mothers meeting inclusion criteria, and 4158 (69.2%) were classified as lactating at the 2-month well-child visit. Among those classified as lactating, the most common medication classes dispensed around the 2-month well-child visit were oral progestin contraceptives (19.1%), selective serotonin reuptake inhibitors (8.8%), first generation cephalosporins (4.3%), thyroid hormones (3.5%), nonsteroidal anti-inflammatory agents (3.4%), penicillinase-resistant penicillins (3.1%), topical corticosteroids (2.9%), and oral imidazole-related antifungals (2.0%). The most common medication classes were similar around the 4 and 6-month well-child visits although prevalence estimates were often lower. Progestin-only contraceptives, antidepressants, and antibiotics were the most dispensed medications among lactating mothers. With routine collection of breastfeeding information, mother-infant linked EHR data may overcome limitations in previous studies of medication utilization during lactation. These data should be considered for studies of medication safety during lactation given the need for human safety data.