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Frontiers in Oncology 2022The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients...
BACKGROUND
The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins.
STUDY DESIGN
Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA".
RESULTS
A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months.
CONCLUSIONS
Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.
PubMed: 36185260
DOI: 10.3389/fonc.2022.965029 -
American Journal of Obstetrics and... Jun 2018Data evaluating the impact of contraceptives on the vaginal microbiome are limited and inconsistent.
BACKGROUND
Data evaluating the impact of contraceptives on the vaginal microbiome are limited and inconsistent.
OBJECTIVE
We hypothesized that women initiating copper intrauterine device use would have increased bacterial vaginosis and bacterial vaginosis-associated microbes with use compared to women initiating and using hormonal contraceptive methods.
STUDY DESIGN
Vaginal swabs (N = 1047 from 266 participants seeking contraception) for Nugent score determination of bacterial vaginosis and quantitative polymerase chain reaction analyses for assessment of specific microbiota were collected from asymptomatic, healthy women aged 18-35 years in Harare, Zimbabwe, who were confirmed to be free of nonstudy hormones by mass spectrometry at each visit. Contraception was initiated with an injectable (depot medroxyprogesterone acetate [n = 41], norethisterone enanthate [n = 44], or medroxyprogesterone acetate and ethinyl estradiol [n = 40]), implant (levonorgestrel [n = 45] or etonogestrel [n = 48]), or copper intrauterine device (n = 48) and repeat vaginal swabs were collected after 30, 90, and 180 days of continuous use. Self-reported condom use was similar across all arms at baseline. Quantitative polymerase chain reaction was used to detect Lactobacillus crispatus, L jensenii, L gasseri/johnsonii group, L vaginalis, L iners, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera-like bacterium phylotype I from swabs. Modified Poisson regression and mixed effects linear models were used to compare marginal prevalence and mean difference in quantity (expressed as gene copies/swab) prior to and during contraceptive use.
RESULTS
Bacterial vaginosis prevalence increased in women initiating copper intrauterine devices from 27% at baseline, 35% at 30 days, 40% at 90 days, and 49% at 180 days (P = .005 compared to marginal prevalence at enrollment). Women initiating hormonal methods had no change in bacterial vaginosis prevalence over 180 days. The mean increase in Nugent score was 1.2 (95% confidence interval, 0.5-2.0; P = .001) in women using copper intrauterine devices. Although the frequency and density of beneficial lactobacilli did not change among intrauterine device users over 6 months, there was an increase in the log concentration of G vaginalis (4.7, 5.2, 5.8, 5.9; P = .046) and A vaginae (3.0, 3.8, 4.6, 5.1; P = .002) between baseline and 30, 90, and 180 days after initiation. Among other contraceptive groups, women using depot medroxyprogesterone acetate had decreased L iners (mean decrease log concentration = 0.8; 95% confidence interval, 0.3-1.5; P = .004) and there were no significant changes in beneficial Lactobacillus species over 180 days regardless of contraceptive method used.
CONCLUSION
Copper intrauterine device use may increase colonization by bacterial vaginosis-associated microbiota, resulting in increased prevalence of bacterial vaginosis. Use of most hormonal contraception does not alter vaginal microbiota.
Topics: Adult; Contraceptive Agents, Female; DNA, Bacterial; Desogestrel; Drug Implants; Ethinyl Estradiol; Female; Gardnerella vaginalis; Humans; Intrauterine Devices, Copper; Lactobacillus crispatus; Lactobacillus gasseri; Levonorgestrel; Medroxyprogesterone Acetate; Megasphaera; Microbiota; Norethindrone; Polymerase Chain Reaction; Protective Factors; Risk Factors; Vagina; Vaginosis, Bacterial; Young Adult
PubMed: 29505773
DOI: 10.1016/j.ajog.2018.02.017 -
Contraception Sep 2016Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and... (Review)
Review
BACKGROUND
Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes.
OBJECTIVES
We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs.
SEARCH STRATEGY
We searched the PubMed database for all articles published from database inception through December 2014.
SELECTION CRITERIA
We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects).
RESULTS
Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association.
CONCLUSION
The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence.
Topics: Breast Feeding; Child Development; Contraception; Contraceptives, Oral, Hormonal; Drug Implants; Female; Humans; Infant; Intrauterine Devices; Levonorgestrel; Medroxyprogesterone Acetate; Progestins; Randomized Controlled Trials as Topic
PubMed: 26410174
DOI: 10.1016/j.contraception.2015.09.010 -
Contraception Jul 2016To describe medroxyprogesterone acetate (MPA) levels among Kenyan depot medroxyprogesterone acetate (DMPA) users in the FEM-PrEP HIV prevention trial, and to compare MPA... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To describe medroxyprogesterone acetate (MPA) levels among Kenyan depot medroxyprogesterone acetate (DMPA) users in the FEM-PrEP HIV prevention trial, and to compare MPA levels between ARV for HIV prevention (treatment) and placebo groups.
STUDY DESIGN
We measured MPA in previously collected plasma samples from 63 Kenyan trial participants who used DMPA for one or two complete intervals. We separately assessed MPA levels among the nine DMPA users who became pregnant at this site.
RESULTS
Mean MPA levels at the end of each 12week injection interval were 0.37ng/ml (95% CI: 0.25, 1.99) and 0.28ng/ml (95% CI: 0.19, 1.22) among participants assigned TDF/FTC and 0.49 (95% CI: 0.40, 1.27) and 0.39 (95% CI: 0.31, 1.17) among those assigned placebo. The difference between groups was not statistically significant overall, or in an analysis which adjusted for the observed low adherence to TDF/FTC. Unanticipated findings of this analysis were low 12-week MPA levels among DMPA users in both study arms. Of 61 women who contributed data for the first DMPA injection interval, 26.2% had MPA levels<0.1ng/ml and 9.8% had levels below the detection level (0.02ng/ml) at 12weeks post-injection. Levels were similar at the end of the second injection interval. Five of nine women who became pregnant had levels below 0.15ng/mL at the time of their last negative pregnancy test.
CONCLUSIONS
Use of TDF/FTC did not appear to affect serum MPA levels, however we found lower than expected MPA concentrations at the end of the dosing interval among DMPA users in the FEM-PrEP trial, the cause of which are unknown.
IMPLICATIONS
This study presents some of the few available data on MPA levels among DMPA users in Africa. The low levels among users described here, together with a number of pregnancies among DMPA users, are potentially concerning and require further investigation.
Topics: Adolescent; Adult; Contraceptive Agents, Female; Delayed-Action Preparations; Drug Interactions; Emtricitabine; Female; HIV Infections; Humans; Kenya; Medroxyprogesterone Acetate; Pre-Exposure Prophylaxis; Pregnancy; Pregnancy Tests; Tenofovir; Young Adult
PubMed: 26972780
DOI: 10.1016/j.contraception.2016.03.003 -
Contraception Nov 2019To compare medroxyprogesterone acetate (MPA) concentrations between HIV-positive women on antiretroviral therapy (ART) and HIV-negative women initiating depot... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To compare medroxyprogesterone acetate (MPA) concentrations between HIV-positive women on antiretroviral therapy (ART) and HIV-negative women initiating depot medroxyprogesterone (DMPA) injectable.
STUDY DESIGN
Secondary analysis of 28 HIV-positive women on non-nucleoside reverse transcriptase inhibitor-containing ART regimens and 10 HIV-negative women randomized to initiate DMPA in a clinical trial of progestin contraception in Malawi.
RESULTS
MPA concentrations were significantly lower among HIV-positive women on ART, compared with HIV-negative women, at week 4 and week 13 (p=.03 for both), but not at day 3 or week 26 post-DMPA initiation.
CONCLUSIONS
Antiretroviral medications may affect MPA metabolism in HIV-positive African women.
Topics: Adult; Anti-HIV Agents; Contraception; Contraceptive Agents, Female; Delayed-Action Preparations; Female; HIV Infections; Humans; Malawi; Medroxyprogesterone Acetate; Progestins; Treatment Outcome; Young Adult
PubMed: 31374188
DOI: 10.1016/j.contraception.2019.07.144 -
Expert Opinion on Pharmacotherapy Oct 2017Endometriosis is an estrogen-dependent chronic inflammatory disorder that requires a life-long management plan. Long-term adherence to treatment is pivotal to ensure an... (Review)
Review
Endometriosis is an estrogen-dependent chronic inflammatory disorder that requires a life-long management plan. Long-term adherence to treatment is pivotal to ensure an effective clinical management. In this optic, one of the cornerstone of endometriosis medical treatment is represented by progestins. Areas covered: This narrative review examines the clinical efficacy, safety and tolerability of oral and depot progestins used in the treatment of endometriosis. The material included in the current manuscript was obtained with a MEDLINE search through PubMed from inception until February 2017. Expert opinion: Progestins are effective in controlling pain symptoms in the majority of women with endometriosis, and their effect seems not inferior to that achieved with other compounds used to treat the disease, such as gonadotropin-releasing hormone agonist. Available progestins include a broad range of both oral and depot compounds, and represent, in most cases, an inexpensive treatment option. In addition, progestins do not increase significantly thrombotic risk and could be adopted in those women with metabolic or cardiovascular contraindication to estrogen-progestins. The choice between the different available compounds should be tailored for every woman with preference to the most cost-effective treatment, depending on the most complained symptom and disease location.
Topics: Administration, Oral; Clinical Trials as Topic; Delayed-Action Preparations; Endometriosis; Female; Humans; Pain; Precision Medicine; Progestins; Treatment Outcome
PubMed: 28914561
DOI: 10.1080/14656566.2017.1381086 -
Sovremennye Tekhnologii V Meditsine 2021This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the... (Review)
Review
This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the pharmacological action of progestins have been studied. Data on the clinical use of gestagens by nosological groups are presented. Particular attention is paid to progesterone, megestrol acetate, medroxyprogesterone acetate due to broadening of their spectrum of action. The possibilities of using gestagens as neuroprotectors, immunomodulators, and chemosensitizers are considered.
Topics: Medroxyprogesterone; Medroxyprogesterone Acetate; Megestrol; Progesterone; Progestins
PubMed: 34513071
DOI: 10.17691/stm2021.13.1.11 -
Molecular Pharmacology Jan 2022The cation channel of sperm (CatSper) is the principal entry point for calcium in human spermatozoa and its proper function is essential for successful fertilization. As...
The cation channel of sperm (CatSper) is the principal entry point for calcium in human spermatozoa and its proper function is essential for successful fertilization. As CatSper is potently activated by progesterone, we evaluated a range of steroids to define the structure-activity relationships for channel activation and found that CatSper is activated by a broad range of steroids with diverse structural modifications. By testing steroids that failed to elicit calcium influx as inhibitors of channel activation, we discovered that medroxyprogesterone acetate, levonorgestrel, and aldosterone inhibited calcium influx produced by progesterone, prostaglandin E, and the fungal natural product -sirenin, but these steroidal inhibitors failed to prevent calcium influx in response to elevated K and pH. In contrast to these steroid antagonists, we demonstrated for the first time that the T-type calcium channel blocker ML218 acts similarly to mibefradil, blocking CatSper channels activated by both ligands and alkalinization/depolarization. These T-type calcium channel blockers produced an insurmountable blockade of CatSper, whereas the three steroids produced antagonism that was surmountable by increasing concentrations of each activator, indicating that the steroids selectively antagonize ligand-induced activation of CatSper rather than blocking channel function. Both the channel blockers and the steroid antagonists markedly reduced hyperactivated motility of human sperm assessed by computer-aided sperm analysis, consistent with inhibition of CatSper activation. Unlike the channel blockers mibefradil and ML218, which reduced total and progressive motility, medroxyprogesterone acetate, levonorgestrel, and aldosterone had little effect on these motility parameters, indicating that these steroids are selective inhibitors of hyperactivated sperm motility. SIGNIFICANCE STATEMENT: The steroids medroxyprogesterone acetate, levonorgestrel, and aldosterone selectively antagonize progesterone- and prostaglandin E-induced calcium influx through the CatSper cation channel in human sperm. In contrast to T-type calcium channel blockers that prevent all modes of CatSper activation, these steroid CatSper antagonists preferentially reduce hyperactivated sperm motility, which is required for fertilization. The discovery of competitive antagonists of ligand-induced CatSper activation provides starting points for future discovery of male contraceptive agents acting by this unique mechanism.
Topics: Aldosterone; Alprostadil; Azabicyclo Compounds; Benzamides; Calcium Channels; Dose-Response Relationship, Drug; Humans; Levonorgestrel; Male; Progesterone; Semen; Sperm Motility; Steroids; Structure-Activity Relationship
PubMed: 34718225
DOI: 10.1124/molpharm.121.000349 -
AIDS Research and Human Retroviruses Aug 2020Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone... (Comparative Study)
Comparative Study Randomized Controlled Trial
Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD), and the levonorgestrel (LNG) implant on markers of HIV disease progression at the time of HIV detection and 3 months postdetection and time from detection to CD4 count <350 cells/mm. Among women initiating antiretroviral therapy (ART), we studied the effect of contraceptive group on time from ART initiation to viral load (VL) <40 copies/mL. We included women 16-35 years randomized to DMPA-IM, copper IUD, or LNG implant with incident HIV infection during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial ( = 382). We analyzed HIV VL and CD4 cell count according to participants' randomized method and also conducted a "continuous use" analysis that excluded follow-up time after method discontinuation. We used adjusted linear models to compare mean VL and CD4 cell levels by contraceptive group up to the time of ART initiation. We compared time from HIV detection to CD4 count <350 cells/mm and, following ART initiation, time to viral suppression (VL <40 copies/mL) using Cox proportional hazards models. At HIV detection, women allocated to DMPA-IM had lower VL relative to copper IUD (-0.28 log copies/mL; 95% confidence interval [CI]: -0.55 to -0.01) and LNG implant (-0.27, CI: -0.55 to 0.02) and higher mean CD4 than copper IUD users by 66 cells/mm (CI: 11-121). In continuous use analyses women allocated to DMPA-IM progressed to CD4 < 350 cells/mm slower than copper IUD users (hazard ratio [HR] = 0.6, CI: 0.3-1.1), whereas copper IUD users progressed faster than LNG implant users (HR = 1.8, CI: 1.0-3.3). Time to viral suppression was faster for DMPA-IM than copper IUD (HR = 1.5, CI: 1.0-2.3) and LNG implant 1.4 (CI: 0.9-2.2) users. We found no evidence of more rapid early HIV disease progression among women using DMPA-IM than among women using copper IUD or LNG implant. Our finding of more rapid progression among copper IUD compared with DMPA-IM users should be interpreted cautiously.
Topics: Adolescent; Adult; CD4 Lymphocyte Count; Disease Progression; Female; HIV Infections; Hormonal Contraception; Humans; Intrauterine Devices, Copper; Levonorgestrel; Medroxyprogesterone Acetate; Proportional Hazards Models; Viral Load; Young Adult
PubMed: 32394723
DOI: 10.1089/AID.2020.0015 -
The Primary Care Companion For CNS... Nov 2023
Topics: Humans; Medroxyprogesterone Acetate; Paraphilic Disorders; Sex Offenses
PubMed: 37976224
DOI: 10.4088/PCC.23cr03558