RESUMEN
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).
Asunto(s)
Anticonceptivos Femeninos , Acetato de Medroxiprogesterona , Noretindrona , Globulina de Unión a Hormona Sexual , Testosterona , Humanos , Femenino , Noretindrona/administración & dosificación , Noretindrona/análogos & derivados , Acetato de Medroxiprogesterona/administración & dosificación , Testosterona/sangre , Adulto , Globulina de Unión a Hormona Sexual/metabolismo , Globulina de Unión a Hormona Sexual/análisis , Adolescente , Adulto Joven , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Inyecciones IntramuscularesRESUMEN
Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1ß, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1ß) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.
Asunto(s)
Biomarcadores , Desogestrel , Infecciones por VIH , Levonorgestrel , Acetato de Medroxiprogesterona , Microbiota , Vagina , Humanos , Femenino , Adolescente , Vagina/microbiología , Vagina/inmunología , Vagina/efectos de los fármacos , Infecciones por VIH/inmunología , Microbiota/efectos de los fármacos , Biomarcadores/metabolismo , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/efectos adversos , Acetato de Medroxiprogesterona/farmacología , Adulto Joven , Levonorgestrel/farmacología , Levonorgestrel/administración & dosificación , Desogestrel/administración & dosificación , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Estudios Longitudinales , Progestinas/farmacología , Progestinas/administración & dosificación , ElafinaRESUMEN
RESEARCH QUESTION: Do the various forms of hormonal and non-hormonal contraceptives have any association with ovarian stimulation outcomes, such as oocyte yield and maturation, in patients undergoing planned oocyte cryopreservation (POC)? DESIGN: This retrospective cohort study included all patients who underwent POC cycles between 2011 and 2023. The use of types of contraception before a POC cycle was recorded. The study evaluated the median number of cumulus-oocyte complexes obtained after vaginal oocyte retrieval and the proportion of metaphase II oocytes that underwent vitrification among all the cohorts. RESULTS: A total of 4059 oocyte freezing cycles were included in the analysis. Eight types of contraceptive method were recognized in patients undergoing ovarian stimulation: intrauterine device (IUD), copper (nâ¯=â¯84); IUD, levonorgestrel low dose (<52 mg) (nâ¯=â¯37); IUD, levonorgestrel (nâ¯=â¯192); subdermal etonogestrel implant (nâ¯=â¯14); injectable medroxyprogesterone acetate (nâ¯=â¯11); etonogestrel vaginal ring (nâ¯=â¯142); combined oral contraceptive pills (nâ¯=â¯2349); and norelgestromin transdermal patch (nâ¯=â¯10). The control group included patients not using contraceptives or using barrier or calendar methods (nâ¯=â¯1220). Among all the cohorts the median number of cumulus-oocyte complexes retrieved during oocyte retrieval was comparable (Pâ¯=â¯0.054), and a significant difference in oocyte maturity rate with median number of vitrified oocytes was found (Pâ¯=â¯0.03, P < 0.001, respectively). After adjusting for confounders a multivariate analysis found no association between the type of contraceptive and proportion of metaphase II oocytes available for cryopreservation. CONCLUSIONS: Among the various forms of contraception, none was shown to have an adverse association with oocyte yield or maturation rate in patients undergoing POC.
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Criopreservación , Recuperación del Oocito , Oocitos , Humanos , Femenino , Estudios Retrospectivos , Adulto , Oocitos/efectos de los fármacos , Inducción de la Ovulación/métodos , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/farmacología , Preservación de la Fertilidad/métodosRESUMEN
OBJECTIVE: To estimate the incidence of ovulation suppression within five days of etonogestrel 68 mg implant insertion in the presence of a dominant follicle with and without same-day ulipristal acetate. STUDY DESIGN: This single site non-masked, exploratory randomized trial recruited people age 18-35 years with regular menstrual cycles, no pregnancy risk, and confirmed ovulatory function. We initiated transvaginal ultrasound examinations on menstrual day 7-9 and randomized participants 1:1 to etonogestrel implant alone or with concomitant ulipristal acetate 30 mg oral when a dominant follicle reached ≥14 mm in diameter. We completed daily sonography and serum hormone levels for up to seven days or transitioned to labs alone if sonographic follicular rupture occurred. We defined ovulation as follicular rupture followed by progesterone >3 ng/mL. We calculated point estimates, risk ratios and 95% confidence intervals for ovulation for each group. Ovulation suppression of ≥44% in either group (the follicular rupture suppression rate with oral levonorgestrel emergency contraception), would prompt future method testing. RESULTS: From October 2020 to October 2022, we enrolled 40 people and 39 completed primary outcome assessments: 20 with etonogestrel implant alone (mean follicular size at randomization: 15.2 mm ± 0.9 mm) and 19 with etonogestrel implant + ulipristal acetate (mean follicular size at randomization: 15.4 mm ± 1.2 mm, p = 0.6). Ovulation suppression occurred in 13 (65%) of etonogestrel implant-alone participants (Risk ratio 0.6 (95% CI: 0.3, 1.1), p = 0.08) and seven (37%) of implant + ulipristal acetate participants. CONCLUSIONS: Ovulation suppression of the etonogestrel implant alone exceeds threshold testing for future research while the implant + ulipristal acetate does not. IMPLICATIONS: Data are lacking on midcycle ovulation suppression for the etonogestrel implant with and without oral ulipristal acetate. In this exploratory study, ovulation suppression occurred in 65% of implant participants and 37% of implant + ulipristal acetate participants. Ovulation suppression of the implant alone exceeds threshold testing for future emergency contraception research.
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Anticoncepción Postcoital , Anticonceptivos Femeninos , Norpregnadienos , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Desogestrel , Anticonceptivos Femeninos/farmacología , Anticoncepción Postcoital/métodosRESUMEN
Contraception is a practice with extensive and complicated social and scientific histories. From cycle tracking, to the very first prescription contraceptive pill, to now having over-the-counter contraceptives on demand, family planning is an aspect of healthcare that has undergone and will continue to undergo several transformations through time. This review provides a comprehensive overview of current reversible hormonal and non-hormonal birth control methods as well as their mechanism of action, safety, and effectiveness specifically for individuals who can become pregnant. Additionally, we discuss the latest Food and Drug Administration (FDA)-approved hormonal method containing estetrol and drospirenone that has not yet been used worldwide as well as the first FDA-approved hormonal over-the-counter progestin-only pills. We also review available data on novel hormonal delivery through microchip, microneedle, and the latest FDA-approved non-hormonal methods such as vaginal pH regulators. Finally, this review will assist in advancing female contraceptive method development by underlining constructive directions for future pursuits. Information was gathered from the NCBI and Google Scholars databases using English and included publications from 1900 to present. Search terms included contraceptive names as well as efficacy, safety, and mechanism of action. In summary, we suggest that investigators consider the side effects and acceptability together with the efficacy of contraceptive candidate towards their development.
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Anticonceptivos Femeninos , Estados Unidos , Embarazo , Humanos , Femenino , Anticonceptivos Femeninos/farmacología , Anticoncepción/métodosRESUMEN
OBJECTIVE: To assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm2 IUD (Cu380-IUD). STUDY DESIGN: Single-center, evaluator-masked, randomized study conducted in women aged 18-45 years starting these methods. Primary outcomes were number of bleeding days, self-reported bleeding intensity, Pictorial Blood Assessment Chart (PBAC) score, and blood biochemical values at baseline, months 3, 6, 12, 24, and 36 per 90-day reference periods except for PBAC (months). Secondary objectives were presence/duration/intensity of dysmenorrhea and tolerability. RESULTS: We included 106 women aged 32.5 ± 6.7 years: 55 with LNG13.5-IUD and 51 with Cu380-IUD. Data for LNG13.5-IUD versus Cu380-IUD at baseline and month 36 (both respectively) were as follows: (1) median (25th; 75th percentile) number of bleeding days: 12 (9.0; 15.0) versus 12 (9.0; 15.0), p = 0.82, and 4 (0; 13.7) versus 15 (14.2; 20.0), p < 0.001; (2) mean bleeding intensity: 1.7 for both, p = 0.66, and 0.7 and 2.2, p < 0.001. Forty percent versus 0% presented with amenorrhea at month 36; (3) mean PBAC score (95% Confidence interval (CI): 50.7 (16.6; 84.7) versus 130.4 (95.7; 165.0) at month 1, and 7.9 (-26.7; 42.6) versus 126 (90.7; 161.2), p < 0.001; (4) median (25th; 75th percentile) ferritin levels (Ug/L) 33 (19; 53) versus 30 (19; 45), p = 0.70, and 59 (42; 84) versus 21 (8; 39). We did not observe changes or differences between groups in hemoglobin and hematocrit. The duration and intensity of dysmenorrhea were significantly lower with LNG13.5-IUD versus Cu380-IUD. Adverse events were those expected. CONCLUSIONS: LNG13.5-IUD is associated with a significant reduction in blood loss and dysmenorrhea compared with Cu380-IUD. IMPLICATIONS: Women eligible for a levonorgestrel 13.5 mg intrauterine device (IUD) or a copper 380 mm2 IUD should be informed of the differences in bleeding profiles-one of the main causes for IUD discontinuation-so they can compare this information against their bleeding expectations.
Asunto(s)
Anticonceptivos Femeninos , Dismenorrea , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos Medicados , Femenino , Humanos , Anticonceptivos Femeninos/efectos adversos , Anticonceptivos Femeninos/farmacología , Cobre , Dismenorrea/etiología , Dispositivos Intrauterinos de Cobre/efectos adversos , Dispositivos Intrauterinos Medicados/efectos adversos , Levonorgestrel/efectos adversos , Adulto , Trastornos de la Menstruación/etiología , Menstruación/efectos de los fármacosRESUMEN
BACKGROUND: It is 100 years since the discovery of oestrogen and nearly that since the discovery of progesterone. It is over 50 years since the concept of using intrauterine progesterone. Ten years after its synthesis, the research using levonorgestrel as an intrauterine agent was introduced. AREAS COVERED: The pharmacodynamics and pharmacokinetics of LNG-IUSs and the LNG-IUS 52 mg in particular explain why intrauterine LNG is so highly effective for contraception. When intrauterine LNG is used therapeutically it should ideally be based on clinical monitoring of the pathology being treated rather than a fixed time period While the LNG-IUS 52 mg is probably required for most medical conditions, consideration should be given for using the LNG-IUS 13.5 mg for hyperplasia and endometrial protection during oestrogen therapy and for older women who appear more prone to a low rate of LNG induced breast cancer, although there is not yet an official indication for this. CONCLUSION: The desire for fertility control, therapy for various genital pathological conditions and reduction of repeated endometrial decidualization and inflammatory breakdown and its consequences, and menopausal problems can be aided by intrauterine LNG. This review explains how a contraceptive also became a WHO listed essential medicine.
There are significant differences at many levels in the use of intrauterine levonorgestrel for contraception when compared to using it as a therapeutic.
Asunto(s)
Anticonceptivos Femeninos , Dispositivos Intrauterinos Medicados , Femenino , Humanos , Anciano , Levonorgestrel , Progesterona , Anticonceptivos Femeninos/farmacología , EstrógenosRESUMEN
INTRODUCTION: Hormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone density and biochemical markers of bone metabolism in women taking hormonal contraceptives on entry to basic military training. METHODS: Forty-five female British Army recruits had biochemical markers of bone metabolism, areal bone mineral density (aBMD) and tibial speed of sound (tSOS) measured at the start of basic military training. Participants were compared by their method of hormonal contraception: no hormonal contraception (NONE), combined contraceptive pill (CP) or depot-medroxyprogesterone acetate (DMPA) (20±2.8 years, 1.64±0.63 m, 61.7±6.2 kg). RESULTS: aBMD was not different between groups (p≥0.204), but tSOS was higher in NONE (3%, p=0.014) when compared with DMPA users. Beta C-terminal telopeptide was higher in NONE (45%, p=0.037) and DMPA users (90%, p=0.003) compared with CP users. Procollagen type 1 N-terminal propeptide was higher in DMPA users compared with NONE (43%, p=0.045) and CP users (127%, p=0.001), and higher in NONE compared with CP users (59%, p=0.014). Bone alkaline phosphatase was higher in DMPA users compared with CP users (56%, p=0.044). CONCLUSIONS: DMPA use was associated with increased bone turnover and decreased cortical bone integrity of the tibia. Lower cortical bone integrity in DMPA users was possibly mediated by increased intracortical remodelling, but trabecular bone was not affected by contraceptive use.
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Anticonceptivos Femeninos , Personal Militar , Femenino , Humanos , Densidad Ósea , Acetato de Medroxiprogesterona/farmacología , Anticonceptivos Femeninos/farmacología , Estudios Transversales , BiomarcadoresRESUMEN
PROBLEM: Both luteal phase progesterone (P4) levels and use of the intramuscular (IM) injectable progestin-only contraceptive depo-medroxyprogesterone acetate (DMPA-IM) have been linked to increased S/HIV acquisition in animal, clinical and in vitro models. Several plausible mechanisms could explain MPA-induced HIV-1 acquisition while those for the luteal phase are underexplored. METHOD OF STUDY: Peripheral blood mononuclear cells (PBMCs) were treated with P4 and estrogen at concentrations mimicking the luteal phase, follicular phase or with levels of MPA mimicking peak serum levels in DMPA-IM users. Cells were infected with an R5-tropic infectious molecular clone and HIV-1 infection was measured. A role for the glucocorticoid receptor (GR) was investigated using the GR/PR antagonist RU486. CCR5 protein levels and activation status, assessed by levels of the activation marker CD69, were measured by flow cytometry after treatment in vitro and in PBMCs from naturally-cycling women or DMPA-IM users. RESULTS: Both MPA and luteal phase hormones significantly increased HIV-1 infection in vitro. However, MPA but not luteal phase hormones increased the CD4+/CD8+ T cell ratio, CCR5 protein expression on CD4+ T cells and increased expression of the activation marker CD69. The GR is involved in MPA-induced, but not luteal phase hormone-induced increased HIV-1 infection. In DMPA-IM users, the frequency of CCR5-expressing CD3+ and CD8+ cells was higher than for women in the luteal phase. CONCLUSIONS: MPA increases HIV-1 infection in a manner different from that of luteal phase hormones, most likely involving the GR and at least in part changes in the frequency and/or expression of CCR5 and CD69.
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Anticonceptivos Femeninos , Infecciones por VIH , VIH-1 , Femenino , Humanos , Anticonceptivos Femeninos/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Leucocitos Mononucleares/metabolismo , Acetato de Medroxiprogesterona/farmacología , Ciclo Menstrual , Progesterona , Receptores de Glucocorticoides/metabolismoRESUMEN
BACKGROUND: Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells. METHODS: Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry. RESULTS: Unlike the LNG implant or copper-IUD, DMPA-IM was associated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4ß7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non-Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post-DMPA-IM (P = .03), although this did not influence barrier function. CONCLUSIONS: Our data suggest that DMPA-IM-driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity. CLINICAL TRIALS REGISTRATION: NCT02550067.
Asunto(s)
Anticonceptivos Femeninos , Infecciones por VIH , Femenino , Humanos , Anticonceptivos Femeninos/farmacología , Cobre , Susceptibilidad a Enfermedades , VIH , Infecciones por VIH/epidemiología , Levonorgestrel , Acetato de Medroxiprogesterona/farmacología , Proteómica , Sudáfrica , VaginaRESUMEN
PROBLEM: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation. METHODS: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors. RESULTS: Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines. CONCLUSION: We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.
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Anticonceptivos Femeninos , Infecciones por VIH , Anticonceptivos Femeninos/efectos adversos , Anticonceptivos Femeninos/farmacología , Citocinas , Femenino , Genitales , Infecciones por VIH/epidemiología , Humanos , Inmunidad Innata , Inflamación , Dispositivos Intrauterinos de Cobre/efectos adversos , Levonorgestrel/efectos adversos , Levonorgestrel/farmacología , Acetato de Medroxiprogesterona/efectos adversos , Acetato de Medroxiprogesterona/farmacologíaRESUMEN
BACKGROUND: Ulipristal acetate 30 mg became available as prescription-only emergency contraception in British Columbia, Canada, in September 2015, as an addition to over-the-counter levonorgestrel emergency contraception. In this study, we determined dispensing and practice use patterns for ulipristal acetate, as well as facilitators of and barriers to emergency contraception for physicians, pharmacists and patients in BC. METHODS: In the quantitative component of this mixed-methods study, we examined ulipristal acetate use from September 2015 to December 2018 using a database that captures all outpatient prescription dispensations in BC (PharmaNet) and another capturing market sales numbers for all oral emergency contraception in BC (IQVIA). We analyzed the quantitative data descriptively. We conducted semistructured interviews from August to November 2019, exploring barriers and facilitators affecting the use of ulipristal acetate. We performed iterative qualitative data collection and thematic analysis guided by Michie's Theoretical Domains Framework. RESULTS: Over the 3-year study period, 318 patients filled 368 prescriptions for ulipristal acetate. Use of this agent increased between 2015 and 2018. However, levonorgestrel use by sales (range 118 897-129 478 units/yr) was substantially higher than use of ulipristal acetate (range 128-389 units/yr). In the 39 interviews we conducted, from the perspectives of 12 patients, 12 community pharmacists, and 15 prescribers, we identified the following themes and respective theoretical domains as barriers to access: low awareness of ulipristal acetate (knowledge), beliefs and experiences related to shame and stigma (beliefs about consequences), and multiple health system barriers (reinforcement). INTERPRETATION: Use of ulipristal acetate in BC was low compared with use of levonorgestrel emergency contraception; lack of knowledge, beliefs about consequences and health system barriers may be important impediments to expanding use of ulipristal acetate. These findings illuminate potential factors to explain low use of this agent and point to the need for additional strategies to support implementation.
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Barreras de Comunicación , Anticoncepción Postcoital , Utilización de Medicamentos/estadística & datos numéricos , Levonorgestrel/farmacología , Norpregnadienos/farmacología , Prioridad del Paciente , Colombia Británica/epidemiología , Anticoncepción Postcoital/métodos , Anticoncepción Postcoital/psicología , Anticonceptivos Femeninos/farmacología , Cultura , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Prioridad del Paciente/psicología , Prioridad del Paciente/estadística & datos numéricos , Pautas de la Práctica Farmacéutica/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Estigma SocialRESUMEN
The aim of this study was to investigate the effect of a one-rod levonorgestrel implant on the blood chemistry profile, including random blood glucose (RBG), haemoglobin (Hb), alanine transferase (ALT), aspartate transferase (AST), and the lipid profile, including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. This prospective cohort study was conducted at Raden Saleh Clinic, Jakarta, from 2010 to 2012. The implants were inserted subdermally in 30 patients. The subjects were evaluated every 6 month up to 2 years. Bivariate analysis using t-test or Wilcoxon signed rank test was performed for all variables. p < 0.05 was considered a significant value. The Hb, RBG, AST, and lipid profile levels were significantly different before and 6 months after one-rod implant insertion (p < 0.05). However, for 24 months, all of the parameters were still within normal limits and did not differ clinically. One-rod levonorgestrel implant insertion has a minimal effect on all blood chemistry profiles.
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Análisis Químico de la Sangre/métodos , Anticonceptivos Femeninos/administración & dosificación , Levonorgestrel/administración & dosificación , Lípidos/sangre , Adulto , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ensayos Clínicos Fase II como Asunto , Anticonceptivos Femeninos/farmacología , Implantes de Medicamentos , Femenino , Humanos , Levonorgestrel/farmacología , Estudios Prospectivos , Triglicéridos/sangre , Adulto JovenRESUMEN
BACKGROUND: Azadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action. PURPOSE: The present review aims to summarize the efficiency of A. indica treatment as a contraceptive. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. RESULTS: A total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 2005 and 2009. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles. CONCLUSION: Although A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive.
Asunto(s)
Azadirachta/química , Anticonceptivos/farmacología , Abortivos/química , Abortivos/farmacología , Animales , Anticonceptivos Femeninos/química , Anticonceptivos Femeninos/farmacología , Medicina Basada en la Evidencia , Femenino , Flores/química , Humanos , Masculino , Fitoquímicos/análisis , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Plantas Medicinales/química , Semillas/química , Espermatogénesis/efectos de los fármacosRESUMEN
BACKGROUND: Access to safe, effective, and affordable contraception is important for women's health and essential to mitigate maternal and fetal mortality rates. The progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) is a popular contraceptive choice with a low failure rate and convenient administration schedule. AIM: In this review, we compiled observational data from human cohorts that examine how DMPA influences the mucosal biology of the female genital tract (FGT) that are essential in maintaining vaginal health, including resident immune cells, pro-inflammatory cytokines, epithelial barrier function, and the vaginal microbiome MATERIALS AND METHODS: This review focused on the recent published literature published in 2019 and 2020. RESULTS: Recent longitudinal studies show that DMPA use associates with an immunosuppressive phenotype, increase in CD4+CCR5+ T cells, and alterations to growth factors. In agreement with previous meta-analyses, DMPA use is associated with minimal effects of the composition of the vaginal microbiome. Cross-sectional studies associate a more pro-inflammatory relationship with DMPA, but these studies are confounded by inherent weaknesses of cross-sectional studies, including differences in study group sizes, behaviors, and other variables that may affect genital inflammation. DISCUSSION & CONCLUSION: These recent results indicate that the interactions between DMPA and the vaginal mucosa are complex emphasizing the need for comprehensive longitudinal studies that take into consideration the measurement of multiple biological parameters.
Asunto(s)
Anticonceptivos Femeninos/farmacología , Acetato de Medroxiprogesterona/farmacología , Membrana Mucosa/efectos de los fármacos , Vagina/efectos de los fármacos , Preparaciones de Acción Retardada , Femenino , Genitales Femeninos , Humanos , Microbiota/efectos de los fármacos , Vagina/microbiologíaRESUMEN
Despite the existence of a variety of contraceptive products for women, as well as decades of research into the prevention and treatment of human immunodeficiency virus (HIV), there is still a globally unmet need for easily accessible, acceptable, and affordable products to protect women's sexual and reproductive health. Microarray patches (MAPs) are a novel platform being developed for the delivery of hormonal contraception and antiretroviral drugs. MAPs provide enhanced drug delivery to the systemic circulation via the transdermal route when compared to transdermal patches, oral and injectable formulations. These minimally invasive patches can be self-administered by the user, reducing the burden on health care personnel. Since MAPs represent needle-free drug delivery, no sharps waste is generated after application, thereby eliminating possible MAP reuse and risk of needle-stick injuries. This review discusses the administration of contraceptive and antiretroviral drugs using MAPs, their acceptability by end-users, and the future perspective of the field.
Asunto(s)
Fármacos Anti-VIH/farmacología , Anticonceptivos Femeninos/farmacología , Infecciones por VIH/prevención & control , VIH/efectos de los fármacos , Análisis por Micromatrices , Sistemas de Liberación de Medicamentos , Femenino , HumanosRESUMEN
Tigers (Panthera tigris spp.) are endangered in the wild; ensuring sustainable insurance populations requires careful planning within zoological collections. In captive situations, contraceptives are often used to control breeding and ensure genetically viable populations that contain manageable numbers of animals; reversible contraceptives are ideal because they offer flexibility for breeding management. Historically, synthetic progestins, such as melengestrol acetate implants, were used in female tigers, but these are associated with an increased risk of reproductive pathology and subsequent infertility. Recent management advice to ex-situ collections has been to transition to the use of gonadotropin-releasing hormone agonists, such as deslorelin acetate implants, which do not appear to have a similar risk of reproductive pathology but are associated with highly variable reversal times in exotic felids. Using data from 917 contraceptive records in female tigers captured by the Association of Zoos and Aquariums Reproductive Management Center and the European Association of Zoos and Aquaria Reproductive Management Group's joint Contraception Database and from supplementary surveys, this study reviews the changing use of contraceptives in captive female tigers. The aim was to describe the historical and current use of contraceptives and provide a comprehensive assessment on the use of deslorelin implants, including data on product protocols, efficacy, pathology, and reversibility. This study determined that current dose, frequency, reversibility, and anatomical placement sites of deslorelin implants are highly variable, indicating that specific, readily available, unified, evidence-based recommendations on the use of deslorelin would be useful for future contraceptive use in managed tiger populations.
Asunto(s)
Animales de Zoológico , Anticonceptivos Femeninos/farmacología , Tigres/fisiología , Pamoato de Triptorelina/análogos & derivados , Animales , Femenino , Estudios Retrospectivos , Pamoato de Triptorelina/administración & dosificación , Pamoato de Triptorelina/farmacologíaRESUMEN
Endometriosis is a common gynaecological pathology characterized by the presence of endometrial tissue outside the uterine cavity, and the most frequent locations of endometriosis are ovaries and posterior compartment of the pelvis. In this paper we report the case of a rare bilateral endometriosis location of posas muscle diagnosed and treated in a 25-year-old patient. This is the third case of psoas endometriosis location reported, but the first one successfully treated by hormone estrogen-progestogen treatment alone. Psoas endometriosis is a rare location and the medical management in first line can be an alternative to surgery and provide optimal patient relief.
Asunto(s)
Endometriosis/tratamiento farmacológico , Músculos Psoas/anomalías , Adulto , Anticonceptivos Femeninos/farmacología , Anticonceptivos Femeninos/uso terapéutico , Citocromo P-450 CYP1A1/farmacología , Citocromo P-450 CYP1A1/uso terapéutico , Endometriosis/complicaciones , Femenino , Humanos , Levonorgestrel/farmacología , Levonorgestrel/uso terapéutico , Músculos Psoas/efectos de los fármacos , Esteroide Hidroxilasas/farmacología , Esteroide Hidroxilasas/uso terapéuticoRESUMEN
OBJECTIVE: To compare the effects of depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and copper intrauterine device (IUD) on mood and sexual function. METHODS: At the Effective Care Research Unit in South Africa, women already randomized in the ECHO Trial to the three methods were asked to participate in this study. Participants were interviewed at 3 and 12 months after enrollment using the Beck Depression Inventory and Arizona Sexual Experiences Scale, and at 12 months using the WHO-5 Wellbeing Index and the Patient Global Impression scale. RESULTS: A total of 605 women participated. There was little difference in depression at 3 months across the three study groups. Contrary to our hypothesis, at 12 months, depression was lowest among DMPA-IM users (16/167, 9.6%) and highest among IUD users (28/158, 17.7%) (p = 0.032). There was little difference in sexual function at any time-point. More women in the DMPA-IM group felt "very much better" on the PGI scale than in the IUD and LNG implant groups (p = 0.003). CONCLUSION: Depression may be less likely with DMPA-IM than with the other methods 1 year after initiation. Major differences in sexual functioning are unlikely. Unhappiness related to not using DMPA-IM, the most popular method in our setting, may have skewed results. TRIAL REGISTRATION NUMBER: PACTR201706001651380.
Asunto(s)
Depresión/epidemiología , Dispositivos Intrauterinos de Cobre , Levonorgestrel/administración & dosificación , Acetato de Medroxiprogesterona/administración & dosificación , Adulto , Anticoncepción/métodos , Anticonceptivos Femeninos/farmacología , Femenino , Humanos , Levonorgestrel/farmacología , Acetato de Medroxiprogesterona/farmacología , Sudáfrica , Adulto JovenRESUMEN
This study aimed to evaluate the effect of a levonorgestrel-releasing intrauterine system (LNG-IUS) on the sexual function of women. Participants who had abnormal uterine bleeding (AUB) complaints with LNG-IUSs were included (study registration: Kanuni Sultan Suleyman Training and Research Hospital, 2018/10/34). The demographic data of all participants were recorded. The female sexual function index (FSFI) questionnaire was used to participants before the insertion of LNG-IUSs and 6 months after its insertion. FSFI scores were calculated at both timepoints and were compared. The total FSFI score after LNG-IUS insertion was significantly higher than the total FSFI score application (p < .001). The scores of the desire, arousal, lubrication, orgasm, satisfaction and pain categories significantly increased after LNG-IUS compared to those before LNG-IUS. As a result, the present study demonstrated that after LNG-IUS insertion, these women had higher FSFI scores.Impact StatementWhat is already known on this subject? There are many publications in the literature comparing the effects of LNG-IUSs, IUSs, OCs and other contraceptive methods on female sexuality. However, there are markedly few studies that compare sexual function before and after LNG-IUS insertion.What do the results of this study add? The total FSFI score after LNG-IUS insertion was significantly higher than the total FSFI score before the insertion (p < .001). The scores of the desire, arousal, lubrication, orgasm, satisfaction and pain categories significantly increased after LNG-IUS insertion compared to those before the application. The number of participants with FSFI scores ≥26.5 before LNG-IUS insertion was 17 (12.5%), and this number increased to 71 (52.5%) after the applicationWhat are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because there are few researches that compare sexual function before and after LNG-IUS insertion. As a result of our study, sexual dysfunction decreased after LNG-IUS, and the scores increased in all sub-groups together with the total FSFI scores.