Subdermal contraceptive implants and repeat teenage motherhood: Evidence from a major maternity hospital-based program in Uruguay.

Teenage fertility is a social problem because of its private and public costs in countries of different development levels. Reductions in adolescent birth rates do not necessarily follow drops in overall fertility due to the demographic transition model. This paper analyses the impact of a subdermal contraceptive program on repeat teenage motherhood. Using a regression discontinuity design, we find that the intervention reduced mothers' likelihood of having another child in the next 48 months by 10 percentage points. This reduction is not random, and we also identify small positive selection in subsequent births.

Development of Subdermal Implants Using Direct Powder Extrusion 3D Printing and Hot-Melt Extrusion Technologies.

Implants are drug delivery platforms that consist of a drug-polymer matrix with the ability of providing a localized and efficient controlled release of the drug with minimal side effects and achievement of the desired therapeutic outcomes with low drug loadings. Direct powder extrusion (DPE) 3D printing technology involves the extrusion of material through a nozzle of the printer in the form of pellets or powder. The present study aimed at investigating the use of the CELLINK BIO X™ bioprinter using DPE 3D printing technique to fabricate and evaluate the impact of different shapes (cuboid, cylinder, and tube) of raloxifene hydrochloride (RFH)-loaded subdermal implants on the release of RFH from the implants. This study further evaluated the impact of different processing techniques, viz., hot-melt extrusion (HME) technology vs. DPE 3D printing technique, on the release of RFH from the implants fabricated by each processing technique. All the fabricated implants were characterized by XRD, DSC, SEM, and FTIR, and evaluated for their water uptake, mass loss, and in vitro RFH release. The current study successfully demonstrated a great opportunity of controlling and/or tuning the release of RFH from the subdermal implants by altering the implant shape, and hence surface area, and could be a great contribution and/or addition to the personalization of medicines and improvement of patient compliance.

Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug.

GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.

Counseling Women About Sexual Health Effects of Contraceptives.

Background: Choosing a contraceptive method is a pivotal decision for patients, whereas health care professionals (HCPs) face challenges in providing suitable recommendations. Adverse sexual effects often lead to dissatisfaction and discontinuation of contraceptives, underscoring the importance of thorough counseling and shared decision making between HCPs and patients. Objective: This article aims to investigate the relationship between contraceptive methods and female sexual function through a comprehensive review of available literature, emphasizing the importance of considering sexual health in contraceptive prescription and management. Methods: A systematic analysis of existing literature, incorporating studies utilizing validated sexual health questionnaires, was conducted to elucidate the intricate interplay between contraceptives and female sexual function. Results: The review encompasses various contraceptive methods, including combined hormonal contraceptives, progestin-only pills, depot medroxyprogesterone acetate, subdermal contraceptive implants, hormonal intrauterine devices, permanent sterilization, and barrier methods. Insights gleaned from the analysis shed light on the impact of these methods on female sexual health. Conclusion: Comprehensive understanding of the effects of contraceptives on female sexual function is crucial for both HCPs and patients. By integrating sexual health considerations into contraceptive surveillance, compliance can be improved, contraceptive efficacy optimized, and the risk of unwanted pregnancies minimized. This review underscores the significance of tailored counseling and shared decision making in contraceptive management, particularly for cisgender women.

Development and evaluation of raloxifene hydrochloride-loaded subdermal implants using hot-melt extrusion technology.

Implantable drug delivery systems are known to provide great patient compliance and allow for controlled delivery of drugs over a prolonged period of time. This study aimed to prepare novel polycaprolactone/polyethylene glycol-based raloxifene hydrochloride subdermal solid cylindrical implants using a single-step hot-melt extrusion (HME) continuous process, for the provision of a sustained and prolonged release of RX-HCl as a cornerstone and alternative treatment and prevention option of osteoporosis, most especially post-menopausal osteoporosis, and invasive breast cancer, while providing better clinical outcomes by circumventing clinical and biopharmaceutical hurdles like first-pass metabolism and patient non-adherence and incompliance associated with the oral dosage forms of raloxifene hydrochloride. The 11-mm co-rotating twin-screw extruder was used to prepare the implants. The prepared cylindrical-shaped solid implants with dimensions of 10 mm (length) by 2 mm (diameter) were characterized by DSC, PXRD, FTIR, SEM, and in vitro dissolution analysis. Based on the physicochemical characterization of the prepared implants, the HME fabrication technology and optimized process parameters were determined to be acceptable and suitable. The prepared implants showed no obvious burst release and no significant amounts of drug on the surface of the implants. F-1, F-2, and F-3 implant batches showed a maximum cumulative percent drug release of 82.9%, 42.2%, and 20.6%, respectively, in a period of 30 days, and 100% drug release would be expected in a period of about 40 days (F-1), 72 days (F-2), and up to 150 days (F-3) by simple extrapolation. Interestingly, implant batches with a low drug load exhibited a relatively faster and higher rate of release of the drug compared to implant batches with high drug loading. In the present study, a single-step HME process was successfully used to fabricate RX-HCl-loaded subdermal implants, that could potentially be used as a cornerstone regimen in the treatment and prevention of osteoporosis, most especially post-menopausal osteoporosis, by providing release of RX-HCl over a long time period, and avoiding the clinical inconveniences and possible patient incompliance caused by daily administration of the drug.

Breast Cancer Risk with Progestin Subdermal Implants: A Challenge in Patients Counseling.

There is a steady global rise in the use of progestin subdermal implants, where use has increased by more than 20 times in the past two decades. BC risk has been reported with the older progestin only methods such as oral pills, injectables, and intrauterine devices, however, little is known about the risk with subdermal implants. In this review, we aim to update clinicians and researchers on the current evidence to support patient counseling and to inform future research directions. The available evidence of the association between the use of progestin subdermal implants and BC risk is discussed. We provide an overview of the potential role of endogenous progesterone in BC development. The chemical structure and molecular targets of synthetic progestins of relevance are summarized together with the preclinical and clinical evidence on their association with BC risk. We review all studies that investigated the action of the specific progestins included in subdermal implants. As well, we discuss the potential effect of the use of subdermal implants in women at increased BC risk, including carriers of BC susceptibility genetic mutations.

Long-acting reversible contraceptive (LARCs) methods.

Unplanned pregnancy (UP) is a public health problem, which affects millions of women worldwide. Providing long-acting reversible contraceptive (LARC) methods is an excellent strategy to avoid or at least reduce UP, because the effectiveness of these methods is higher than other methods, and is indeed comparable to that of permanent contraception. As the initial introduction of the inert plastic intrauterine device (IUD) and of the six-rod implant, pharmaceutical companies have introduced a copper IUD (Cu-IUD), different models of levonorgestrel-releasing intrauterine system (LNG IUS), and one and two-rod implants, which certainly improved women's LARC options. The main characteristic of LARCs is that they provide high contraceptive effectiveness with a single intervention, and that they can be used for a long time. Emerging evidence from the last few years has demonstrated that it is possible to extend the use of the 52 mg LNG IUS and of the etonogestrel-implant beyond five- and three years, respectively, which adds new value to these LARCs.

Treatment and prevention of HIV infection with long-acting antiretrovirals.

INTRODUCTION: Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance. Unfortunately, drug adherence is often suboptimal and tends to decline over time. Areas covered: New drugs, formulations and delivery systems are being developed for extended-release of antiretrovirals. At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal rings and tenofovir alafenamide subdermal implants are the products in more advanced stages of clinical development. Their pharmacokinetics/dynamics and safety/efficacy are reviewed. Expert commentary: In the absence of eradicative therapy for individuals with HIV infection and protective vaccines for persons at risk, long-term antiretroviral therapy is the best approach for preventing disease progression in patients and halting transmissions, either as result of 'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for uninfected individuals at risk. In all these scenarios, the advent of long-acting antiretrovirals will expand options for overcoming the challenge of suboptimal drug adherence and reduce the burden of HIV infection.

Association between contraceptive implant knowledge and intent with implant uptake among postpartum Malawian women: a prospective cohort study.

BACKGROUND: Long-acting reversible contraception (LARC) can assist women with birth spacing and reduce unintended pregnancies. Sub-Saharan Africa has low uptake of the two available methods of LARC, the subdermal implant and intrauterine contraception (IUC). Our primary objectives were to: 1) calculate the incidence of LARC use among postpartum Malawian women, and 2) assess if LARC knowledge and intent to use LARC were associated with LARC uptake. METHODS: This study was a prospective cohort study of 634 postpartum women who were recruited from the postpartum ward of Bwaila Hospital in Lilongwe, Malawi. Study participants completed a baseline survey in the postpartum ward. Follow-up telephone surveys about contraceptive use were conducted at 3, 6, and 12 months postpartum. Cox proportional hazards regression analysis was performed to evaluate if implant knowledge and intent to use implant were associated with implant uptake. RESULTS: One hundred thirty-seven implant and 10 IUC placements were reported over 12 months of follow-up; given the low rate of IUC uptake, further analysis was only done for implant uptake. The incidence rate for implant uptake was 35.6 per 100 person-years (95 % CI 30.0, 42.2). Correct implant knowledge (adjusted HR = 1.69; 95 % CI 1.06, 2.68) and intent to use implant (adjusted HR 1.95; 95 % CI 1.28, 2.98) were both associated with implant uptake. CONCLUSIONS: More women reported implant use than IUC use in our study. Correct implant knowledge and intent to use implant were both associated with implant uptake, with a stronger association for intent. Interventions to increase LARC uptake should focus on improving LARC knowledge and removing barriers to LARC. TRIAL REGISTRATION: Clinical Trial Registration #: NCT01893021.

Pharmacologic treatment of the ovarian endometrioma.

INTRODUCTION: Treatment of ovarian endometriomas is commonly achieved through laparoscopic surgery and this can be effective in eliminating the disease, although a majority of recent trials documented an adverse effect of surgery on ovarian reserve markers. With the advancement in imaging techniques, ovarian endometriomas are increasingly diagnosed at an earlier stage when the endometrioma may be smaller, less fibrotic and more responsive to medical treatment, making an evaluation of medical options critically important. AREAS COVERED: The review focuses on currently utilized pharmacologic therapies for endometrioma (oral contraceptives, the levonorgestrel-releasing IUS, the hormone-releasing subdermal implant, Implanon); experimental and future treatments are also mentioned (GnRH antagonists, progesterone receptor modulators, antioestrogens, newer subdermal implants and intracystic administration of pharmacologic agents). Finally, the usefulness of post-operative adjuvant medical treatments is discussed Expert opinion: Today, reliable, non-invasive diagnostic procedures of an ovarian endometrioma are available and should be utilized to identify its presence and type of pathology. In a young patient, classic medical therapies such as oral contraceptives and synthetic progestins should be tried first to alleviate symptoms. Only when these regimens fail, should a minimally invasive surgery be envisaged. Following endoscopic surgery, adjuvant medical treatment may reduce recurrence of both symptoms and the lesion.

Postabortion Initiation of Long-Acting Reversible Contraception by Adolescent and Nulliparous Women in New Zealand.

PURPOSE: To describe changes in receipt of immediate postabortion long-acting reversible contraception (LARC) by adolescent and nulliparous women in New Zealand. METHODS: Nationally collected data on immediate postabortion receipt of an intrauterine method (intrauterine device [IUD]/intrauterine system [IUS]) or contraceptive implant were analyzed to describe proportions and demographic characteristics of women receiving LARC between 2007 and 2013. Changes in uptake over time were presented for adolescent, nulliparous, and parous women. RESULTS: Postabortion LARC uptake increased between 2007 and 2013, rising from 7.9% to 42.7% for adolescents and from 8.8% to 36.9% for nulliparous women. The increase was highest among nulliparous adolescents with a seven-fold increase in LARC uptake between 2007 and 2013. Adolescents had a five-fold increase and nulliparous women (of all ages) a four-fold increase. In 2013, IUD/IUS use was lowest among adolescents (22.4%) and increased with increasing age (43% by ages 40+ years), whereas implant use was highest among adolescents (20.3%) and decreased with increasing age (to 4.6% by age 40+ years). Nulliparous women had the lowest use of both IUD/IUS and implants in 2013, with 24.6% receiving an intrauterine method (compared with 43.2% for para 3+), and 12.3% an implant (compared with 17.5% for para 3+). CONCLUSIONS: Despite an overall trend toward increased uptake of postabortion LARC by adolescent and nulliparous women, uptake in these groups still lags behind that of parous and older women. Reasons for differential uptake need to be explored and addressed if necessary to ensure all women have equitable access to the most effective methods of contraception.

EVAPIL-R Scale: Continuous development and validation of a tool to assess patient-reported tolerability of different contraceptive methods in longitudinal studies.

OBJECTIVE: The objective of this study was to modify the EVAPIL, a questionnaire designed to assess user-reported tolerability of combined oral contraceptives (COCs) in cross-sectional studies, to make it appropriate for assessing the tolerability of intrauterine systems (IUSs), subdermal implants, and COCs in longitudinal studies. METHODS: Development of the EVAPIL-Revised (EVAPIL-R) was informed by a targeted literature review, qualitative interviews with IUS-prescribing gynecologists (n = 5), and IUS and implant users in the United States, Germany, and France (n = 36). RESULTS: Evidence generated supports the content validity of the EVAPIL-R for assessing user-reported tolerability of COCs, IUSs, and implants. Modifications to improve the relevance and usability of the questionnaire in longitudinal studies included specification of a defined recall period, addition of separate assessments of frequency and intensity (where relevant), and inclusion of additional items measuring concepts of importance to IUS and implant users (eg, vaginal discharge). CONCLUSIONS: The EVAPIL-R is a valuable tool for use in research and clinical practice to identify tolerability concerns in hormonal contraceptive users. Future research will evaluate the psychometric validity and responsiveness of the EVAPIL-R. Understanding of user-reported tolerability of contraceptive methods is critical for facilitating patient adherence and potentially reducing the number of unintended pregnancies. The EVAPIL-R may be used to facilitate "women-centered" research and contraceptive counseling and provision.