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Contraception May 2021Immediate contraceptive initiation, including start of a method before abortion completion, is a convenient option for women seeking abortion care. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immediate contraceptive initiation, including start of a method before abortion completion, is a convenient option for women seeking abortion care.
OBJECTIVES
To evaluate the effect of systemic hormonal contraception initiation on medical abortion effectiveness and the safety of hormonal contraceptive methods following abortion.
DATA SOURCES
PubMed, Popline, Cochrane Library, and Clinicaltrials.gov.
STUDY ELIGIBILITY CRITERIA
Studies that assessed medical abortion effectiveness after systemic hormonal contraception initiation and the safety of hormonal contraception initiation after abortion.
PARTICIPANTS
Pregnant persons undergoing or who had recently undergone an abortion.
INTERVENTIONS
Initiation of systemic hormonal contraception post abortion or on the day of the first pill of the medical abortion.
STUDY APPRAISAL AND SYNTHESIS METHODS
We assessed study quality using the US Preventive Services Task Force evidence grading system. We created narrative summaries and calculated pooled relative risks when appropriate.
RESULTS
We identified 16 studies for inclusion, 7 randomized controlled trials, and 9 cohorts. Nine studies assessed medical abortion effectiveness with hormonal contraception initiation and generally found no decreased risk of abortion success or increased risk of additional treatment. One fair-quality study reported a small increase in ongoing pregnancy rate with immediate depot medroxyprogesterone (DMPA) compared with delayed DMPA initiation (3.6% vs 0.9%, risk difference 2.7%, 90% confidence interval 0.4-5.6). We identified no bleeding-related safety concerns following hormonal contraception initiation after medical or surgical abortion. Pooled results were too imprecise to draw firm conclusions.
LIMITATIONS
Included studies were poor or fair quality and primarily in high-income or upper-middle-income settings.
CONCLUSIONS
Abortion effectiveness did not differ between immediate vs delayed initiation of most systemic hormonal contraceptive methods after a first trimester medical abortion. However, immediate DMPA initiation did show increased ongoing pregnancy. Bleeding effects with hormonal contraception initiation postabortion appeared minimal.
IMPLICATIONS
Initiating a hormonal contraceptive method after an abortion and as early as the same day as the first pill of the medical abortion is an option if contraception is desired. The slight increase in ongoing pregnancy with immediate DMPA initiation highlights the importance of information provision during contraceptive counseling.
Topics: Abortion, Induced; Contraception; Family Planning Services; Female; Hormonal Contraception; Humans; Pregnancy
PubMed: 33548267
DOI: 10.1016/j.contraception.2021.01.017 -
Medicina (Kaunas, Lithuania) Aug 2019: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated,... (Review)
Review
: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. : Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. : Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). : For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.
Topics: Disease Progression; Estrogen Replacement Therapy; Estrogens; Female; Humans; Leiomyoma; Postmenopause; Progestins; Ultrasonography; Uterine Neoplasms; Uterus
PubMed: 31480288
DOI: 10.3390/medicina55090549 -
The Journal of Steroid Biochemistry and... Mar 2024Progestins used in hormonal contraceptives and menopausal hormone therapy (MHT) have been linked to increased breast cancer risk. Whether the association holds for all...
Progestins used in hormonal contraceptives and menopausal hormone therapy (MHT) have been linked to increased breast cancer risk. Whether the association holds for all progestins is unclear and the underlying mechanisms remain poorly understood. We directly compared the effects of four progestins (medroxyprogesterone acetate (MPA), norethisterone acetate (NET-A), levonorgestrel (LNG) and drospirenone (DRSP)) to each other and the natural progestogen progesterone (P) on selected cancer hallmarks. To provide mechanistic insight into these effects, we assessed the role of the progesterone receptor (PR), and the extracellular signal-related kinase (ERK1/2) and c-Jun N terminal (JNK) signaling pathways. We showed that the increased proliferation of the luminal T47D breast cancer cell line by P and all progestins, albeit to different extents, was inhibited by PR knockdown and inhibition of both the ERK1/2 and JNK pathways. While knockdown of the PR also blocked the upregulation of MKI67 and CCND1 mRNA expression by selected progestogens, only a role for the ERK1/2 pathway could be established in these effects. Similarly, only a role for the ERK1/2 pathway could be confirmed for progestogen-induced colony formation, whereas both the ERK1/2 and JNK pathways were required for cell migration in response to the three older progestins implicated in the etiology of breast cancer, MPA, NET-A and LNG. Together our results show that all the progestins elicit their effects on cell proliferation via a mechanism requiring the PR, ERK1/2 and JNK pathways. While the ERK1/2 and JNK pathways are also required for increased cell migration by the older progestins, only a role for the ERK1/2 pathway could be established in their effects on colony formation. Notably, the cytoplasmic PR was not needed for activation of the ERK1/2 pathway by the progestogens. Given that DRSP showed significantly lower proliferation than MPA and NET-A, and that it had no effect on breast cancer cell migration and colony formation, hormonal formulations containing the newer generation progestin DRSP may provide a better benefit/risk profile towards breast cancer than those containing the older generation progestins.
Topics: Humans; Female; Progestins; Breast Neoplasms; MAP Kinase Signaling System; Progesterone; Medroxyprogesterone Acetate; Levonorgestrel; Receptors, Progesterone; Receptors, Estrogen
PubMed: 38048919
DOI: 10.1016/j.jsbmb.2023.106440 -
Gynecological Endocrinology : the... Dec 2023To compare the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in infertility patients with normal ovarian reserve function... (Review)
Review
OBJECTIVE
To compare the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in infertility patients with normal ovarian reserve function undergoing invitro fertilization and embryo transfer.
METHODS
A retrospective cohort study was conducted to analyze the clinical data of 2013 cycles of patients with normal ovarian reserve function who underwent invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in the Department of Human Reproductive Center, Renmin Hospital, Hubei University of Medicine from January 2018 and June 2020. The PPOS protocol group included 679 cycles and GnRH-along protocol group included 1334 cycles, the pregnancy outcomes were compared between the two groups.
RESULTS
The duration of Gn used and total Gn used dosage in the PPOS protocol group were less than those in the GnRH-along protocol group (Duration of Gn used: 10.05 ± 1.48 vs 11.90 ± 1.85 d, < 0.001; Total Gn used dosage: 1944.49 ± 533.61 vs 2661.34 ± 987.97 IU, < 0.001); The LH levels were significantly higher on HCG trigger day in PPOS protocol compared to GnRH-a long protocol (2.8 ± 1 ± 1.07 vs 1.01 ± 0.62 IU/L, < 0.001), the E2 levels on HCG trigger day in PPOS protocol group was lower than that in the GnRH-a long protocol group (2135.92 ± 1387.00 vs 2417.01 ± 1010.70 pg/mL, < 0. 001). The number of oocytes retrieved in the PPOS protocol group was lower than that in the GnRH-along protocol group (8.03 ± 2.86 vs 9.47 ± 2.64, < 0.001). No significant differences were found in pregnancy outcome including clinical pregnancy rate, early miscarriage rate and ectopic pregnancy rate between the two group ( > 0.05); In addition, no severe OHSS occurred in the PPOS protocol group during ovulation induction, while 11 patients of severe ovarian hyperstimulation syndrome (OHSS) occurred in GnRH-a long protocol group ( < 0.001).
CONCLUSION
The clinical efficacy of PPOS protocol combining embryo cryopreservation is comparable to that of GnRH-a long protocol in patients with normal ovarian reserve function, and the PPOS protocol is able to reduce the incidence of severe OHSS significantly.
Topics: Female; Pregnancy; Humans; Male; Progestins; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Retrospective Studies; Ovarian Reserve; Semen; Ovulation Induction; Ovarian Hyperstimulation Syndrome; Pregnancy Rate; Steroids
PubMed: 37236243
DOI: 10.1080/09513590.2023.2217263 -
AIDS Research and Human Retroviruses Jan 2022Phosphorylating enzymes (PEs) are responsible for activating nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) such as tenofovir (TFV) and are critical for...
Phosphorylating enzymes (PEs) are responsible for activating nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) such as tenofovir (TFV) and are critical for their conversion to obtain intracellular antiviral activity. However, there are limited data available regarding the expression of PEs and their activity in the female genital tract. This work compared the messenger RNA (mRNA) expression levels of PEs in human female genital tissue, immune cells, and animal models that are commonly used in human immunodeficiency virus (HIV) research. Furthermore, the effect of contraceptive hormones and proinflammatory cytokines on tenofovir diphosphate (TFV-DP) formation and efficacy in human vaginal, epithelial, and immune cells was also evaluated. We found that human vaginal and ectocervical tissues had similar mRNA expression for seven PEs tested. Polymerase chain reaction results revealed that creatine kinase brain (CKB), mitochondrial creatine kinase 1 (CKMT1), mitochondrial creatine kinase 2 (CKMT2), adenylate kinase AK3L1 (AK4), and nucleoside diphosphate kinase 1 (NME1) exhibited a 10- to 10,000-fold higher expression level in a vaginal epithelial cell line, VK2, compared with CD4 T cells ( < .05). Medroxyprogesterone acetate (MPA)/progesterone (P4) and IL-1β/IL-8 treatment resulted in altered TFV-DP levels in VK2 and PM1 cells. MPA and P4 at concentrations above 0.1 μM, as well as IL-1β and IL-8 at concentrations above 10 ng/mL, significantly decreased HIV-1 inhibition in PM1 cells when 1 μM TFV was added. However, this observed effect of hormones and cytokines was abrogated when TFV concentration was raised to 1 mM. These results elucidate the role of PEs in TFV metabolism and provide information regarding differences in PE tissue expression for animal models commonly used in HIV testing. This information can be applied to better understand and interpret data obtained using these models.
Topics: Animals; Anti-HIV Agents; Creatine Kinase, Mitochondrial Form; Female; HIV Infections; HIV-1; Humans; Medroxyprogesterone Acetate; Tenofovir
PubMed: 33567990
DOI: 10.1089/AID.2020.0250 -
Ovariectomized mice and postmenopausal women exhibit analogous loss of genital epithelial integrity.Tissue Barriers Apr 2021Roughly half of all postmenopausal women are affected by the genitourinary syndrome of menopause (GSM). Symptoms of GSM, including vaginal irritation and dyspareunia,...
Roughly half of all postmenopausal women are affected by the genitourinary syndrome of menopause (GSM). Symptoms of GSM, including vaginal irritation and dyspareunia, occur as reduced estrogen (E) production elicits loss of elasticity and other changes in genital tract tissue. While the use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) likewise lowers serum E concentrations in reproductive age women and is associated with decreased genital levels of the cell-cell adhesion molecules desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and impaired genital epithelial barrier function, the relevance of these findings to women in menopause is uncertain. Exploring the impact of menopause on genital epithelial integrity herein, we detected significantly lower levels of DSG1 and DSC1 in ectocervical tissue from menopausal and postmenopausal vs premenopausal women. Using ovariectomized (OVX) mice as a menopause model, we comparably saw significantly lower vaginal tissue levels of DSG1 and DSC1 in OVX mice vs. mice in estrus. Compared to estrus-stage mice and E-treated OVX mice, DMPA-treated ovary-intact mice and OVX mice also exhibited significantly reduced genital epithelial barrier function, greater susceptibility to genital herpes simplex virus type 2 infection, and delayed clearance of genital infection. Current studies thus identify analogous loss of genital epithelial integrity in OVX mice and menopausal and postmenopausal women. By showing that loss of genital epithelial integrity is associated with increased mouse susceptibility to bacterial and viral pathogens, our findings also prioritize the need to resolve if reduced genital epithelial integrity in postmenopausal women is a significant risk factor for genital infection.
Topics: Animals; Epithelium; Female; Genitalia, Female; Humans; Mice; Ovary
PubMed: 33427560
DOI: 10.1080/21688370.2020.1865760 -
The Linacre Quarterly May 2021Hormonal contraceptives have been on the market for over fifty years and, while their formulations have changed, the basic mechanism of action has remained the same....
UNLABELLED
Hormonal contraceptives have been on the market for over fifty years and, while their formulations have changed, the basic mechanism of action has remained the same. During this time, numerous studies have been performed documenting side effects, some of which appear over time, some within weeks or months, but all can have a serious impact on health and quality of life. An effort was made to perform a series of comprehensive literature surveys to better understand immediate and long-term side effects of these agents. The results of this literature review uncovered a number of potential side effects, some of which are acknowledged and many of which are not noted in the prescribing information for these agents. Among the unacknowledged side effects are: an increased risk of HIV transmission for depot medroxyprogesterone acetate (DMPA), and for combination contraceptives breast cancer, cervical cancer, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, depression, mood disorders and suicides (especially among women twenty-five years of age and younger, in the first six months of use), multiple sclerosis, interstitial cystitis, female sexual dysfunction, osteoporotic bone fractures (especially for progesterone-only contraceptives), and fatty weight gain. Misleading prescribing information regarding cardiovascular and thrombotic risks are also noted. Women seeking birth control have a right to be informed and educated about risk avoidance through the use of effective nonhormonal methods like fertility awareness methods. In one case-that of DMPA-the increased risk of HIV acquisition has been conclusively demonstrated to be both real and unique to this drug. Considering the availability of numerous alternatives, there is no justification for the continued marketing of DMPA to the public.
SUMMARY
We reviewed the effect of hormonal contraceptives on women's health. A number of potential side effects were noted including increased risks of breast cancer, cervical cancer, inflammatory bowel disease, lupus, multiple sclerosis, cystitis, bone fractures, depression, mood disorders and suicides, fatty weight gain, and female sexual dysfunction. With the long-acting injectable contraceptives there is an increased risk of getting HIV. Misleading prescribing information regarding the risks of heart attacks, strokes and blood clotting problems were also noted. Women seeking birth control have a right to know about how to avoid these risks by using effective hormone-free Fertility Awareness Methods.
PubMed: 33897046
DOI: 10.1177/0024363920982709 -
Frontiers in Cell and Developmental... 2021Human endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on...
Human endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on cell therapy due to their broad differentiation potential and highly efficient proliferation. In our study, we investigated the characteristics of hEndSCs that were isolated from two sources: endometrium and menstrual blood, which both contain endometrial origin stem cells. Changes in gene and protein expression levels during long-term cultivation and decidualization potential were examined in endometrial stem cells (EndSCs) and menstrual blood stem cells (MenSCs). The decidualization process was induced on early and late passages of hEndSCs using dibutyryl cyclic-AMP (db-cAMP) and medroxyprogesterone acetate (MPA) agents. We demonstrated that after long-term cultivation of hEndSCs the expression of typical mesenchymal stromal cell surface markers such as CD44, CD73, CD90, CD105 and perivascular marker CD146 remains at a similar level throughout long-term cultivation. Additionally, hematopoietic and endothelial markers CD34, CD45 were also tested, they were negative in all cases. Analyzed stem cells gene markers, such as OCT4, SOX2, NANOG, KLF4, showed similar expression in all passages of hEndSCs. RT-qPCR results demonstrated that the expression of cell cycle control associated genes - CDK2, CCNA2, CCNE2, p21, p53 and Rb, among all groups was very similar. Expression of genes associated with senescence (ATM, JUND, TOP2A, MYC) was maintained at a similar level throughout passaging. In addition, Western blot analysis was used to assess changes in proteins' levels associated to epigenetics (EZH2, SUZ12, H3K27me3) and cell cycle control (cyclinE1, p53) during long-term cultivation. The levels of proteins associated with epigenetic changes were fluctuated slightly depending on the patient. Also, we demonstrated that in all induced hEndSCs the expression of decidualization markers Prolactin (PRL), IGFBP1 and WNT4 was upregulated. In conclusion, we demonstrated successful decidualization of stem cells derived from two reproductive system resources: endometrium and menstrual blood by using db-cAMP and MPA regardless of the length of the stem cell passaging. According these findings, we suppose that endometrium derived stem cells and menstrual blood derived stem cells could have a potency not only for endometrium tissue regeneration, but could also become a successful therapy for reproductive system disorders, including infertility or recurrent pregnancy loss.
PubMed: 34869358
DOI: 10.3389/fcell.2021.765265 -
Current Issues in Molecular Biology Nov 2021Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as...
Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E), and progesterone (P). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E + medroxyprogesterone acetate (MPA), a potent P receptor agonist, showed significant down-regulation of , , , , , and in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, and were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased expression in untreated human ESCs. These results collectively indicate the importance of and in ESC decidualization and highlight the role of HAND2 in repressing transcription, thereby regulating decidualization.
Topics: Adult; Biomarkers; Cells, Cultured; Decidua; Endometrium; Female; Gene Expression Regulation; Humans; Matrix Metalloproteinases; Middle Aged; Steroids; Stromal Cells; Tissue Inhibitor of Metalloproteinases; Young Adult
PubMed: 34940120
DOI: 10.3390/cimb43030146 -
Scientific Reports Nov 2023There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women...
There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74-0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24-0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35-0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27-0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01-1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.
Topics: Female; Humans; Pregnancy; Black People; Contraceptives, Oral; Leiomyoma; Reproduction; Risk Factors
PubMed: 37919335
DOI: 10.1038/s41598-023-44703-5