-
Contraception Dec 2023This study aimed to evaluate the feasibility and effectiveness of providing bedside family planning services to women with chronic medical conditions in the inpatient... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study aimed to evaluate the feasibility and effectiveness of providing bedside family planning services to women with chronic medical conditions in the inpatient setting.
STUDY DESIGN
We initiated a parallel randomized controlled trial of patients listed as female aged 18 to 44 years who were admitted to the hospital from February 2018 to May 2021 with at least one chronic medical condition associated with lower rates of contraception usage and no documentation of contraception. Patients who confirmed they were not using contraception were enrolled and randomized to one of the three arms. They received bedside family planning counseling and an offer of contraception prior to discharge (oral contraceptive pills, etonogestrel implant, or medroxyprogesterone injection), received a flyer recommending they talk with their outpatient physician about contraception, or received standard care. The primary outcomes were contraception use at 3 months and 12 months after discharge.
RESULTS
Altogether 76 subjects were enrolled and randomized with 22 in the counseling arm and 27 each in the other arms. In the counseling arm, five (23%; 95% CI: 8.0%-45%) elected to receive contraception prior to discharge. Inferential statistics at follow-up were not able to be calculated due to high attrition.
CONCLUSIONS
Providing counseling and offering immediate contraception initiation in the inpatient setting may be a feasible approach to improving contraception access for this population. Additional investigation into the acceptability, efficacy, and generalizability of this approach is warranted.
IMPLICATIONS
Utilizing the inpatient setting may be a feasible approach for delivering contraception counseling to women with chronic medical conditions. This approach merits further study for effectiveness and acceptability. This study highlights the need for contraceptive counseling and initiation to become a standard part of hospital care for pregnancy-capable individuals.
Topics: Pregnancy; Female; Humans; Family Planning Services; Inpatients; Feasibility Studies; Contraception; Counseling
PubMed: 37549724
DOI: 10.1016/j.contraception.2023.110133 -
Acta Bio-medica : Atenei Parmensis Aug 2023Hypogonadism and abnormalities of glucose homeostasis, resulting from iron-induced pituitary and pancreatic β-cell dysfunction respectively, are the most frequently...
Retrospective study on long-term effects of hormone replacement therapy (HRT) and iron chelation therapy on glucose homeostasis and insulin secretion in female ß- thalassemia major (β-TM) patients with acquired hypogonadotropic- hypogonadism (AHH).
BACKGROUND AND AIM
Hypogonadism and abnormalities of glucose homeostasis, resulting from iron-induced pituitary and pancreatic β-cell dysfunction respectively, are the most frequently reported endocrine abnormalities in patients with ß-thalassemia major (β-TM), also identified as transfusion-dependent thalassemia (TDT).
STUDY DESIGN AND PATIENTS
The aim of the present retrospective study was to evaluate the long-term effects of hormone replacement therapy (HRT) on glucose metabolism and insulin secretion/sensitivity during 3-h oral glucose tolerance test (OGTT) in adolescent and young β-TM women with acquired hypogonadototropic -hypogonadism (AHH).Twelve hypogonadal β-TM females with AHH on HRT were followed for 8.26 ± 1.49 years.
RESULTS
At baseline, 10 patients (83.3%) had normal OGTT, 1 patient presented with impaired glucose tolerance (IGT) and 1 patient had an isolated PG level of 165 mg/dL at 1-h during OGTT (H-NGT). At last evaluation, 7 patients (58.4 %) had normal OGTT, while 5 patients (41.6%) had abnormal OGTT. Reduced insulin sensitivity and impaired first-phase insulin secretion were also documented. Three of 4 β-TM patients on treatment with estradiol hemihydrate MX 50 patches plus oral medroxyprogesterone acetate (MPA), associated with a very effective iron chelation therapy, maintained normal glucose tolerance from baseline to last evaluation. Significant adverse events due to HRT or additional endocrine complications were not documented in any cases during the follow-up.
CONCLUSION
Deterioration of glycemia (dysglycemia) occurred in 45.4% (5/11) of thalassemic females on long-term HRT. Additional studies are needed to elucidate the validity of our preliminary observations.
Topics: Adolescent; Female; Humans; beta-Thalassemia; Blood Glucose; Chelation Therapy; Endocrine System Diseases; Glucose; Glucose Intolerance; Homeostasis; Hormone Replacement Therapy; Hypogonadism; Insulin Resistance; Insulin Secretion; Iron; Retrospective Studies; Young Adult
PubMed: 37539597
DOI: 10.23750/abm.v94i4.14631 -
Cureus Jun 2023Background and objective Unplanned pregnancies are very common in the postpartum period, and they often lead to negative outcomes such as abortion, low-birth-weight...
The Acceptance of Postpartum Intrauterine Contraceptive Devices Among Women Who Receive Focused Family Planning Counseling in the Antenatal Period Compared to Those Who Receive Routine Counseling: A Randomized Controlled Trial.
Background and objective Unplanned pregnancies are very common in the postpartum period, and they often lead to negative outcomes such as abortion, low-birth-weight neonates, early delivery, postpartum bleeding, and fetal mortality. In the first 12 months after delivery, closely spaced and unintentional pregnancies can be prevented with postpartum contraception. The postpartum intrauterine contraceptive device (PPIUCD) is a method of family planning that may be used during the first few weeks after giving birth, and it is highly successful, reliable, affordable, non-hormonal, immediately reversible, long-acting, and does not interfere with lactation. Urban and educated women are largely aware of IUCD and its benefits, but the proportion of these women who use them is still small. In light of this, this study aimed to assess if providing focused antenatal counseling led to a greater postpartum IUCD acceptance rate when compared to routine counseling. Method We conducted a randomized controlled trial in the Department of Obstetrics and Gynaecology of a tertiary care center from January 2021 to December 2022. Based on the inclusion and exclusion criteria, 220 women were enrolled and were classified into two groups. Group A comprised 110 women (the focused counseling group) who received focused postpartum family planning (PPFP) counseling, and Group B consisted of the control group involving 110 women who received routine counseling. Results In both groups, the women who inserted IUCD were mostly gravida 2. Additionally, willingness to use IUCD was shown by 68% of women in the focused counseling group and 58% of women in the routine counseling group, and PPIUCD was accepted by 22% of women in the focused counseling group and 9% of women in the routine counseling group. Post-placental insertion was carried out in 18 (75%) cases in the focused counseling group and seven (70%) cases in the routine counseling group. Extended postpartum insertion (insertion within one year of delivery) was carried out in six (25%) cases in the focused counseling group and three (30%) cases in the routine counseling group. The most common reasons for the refusal were a preference for tubal ligation (TL) and a fear of side effects. When the patients were enquired about their contraceptive use over the past year on telephone conversations after one year of delivery, it was observed that 21.81% inserted PPIUCD, 30% used injectable depot-medroxyprogesterone acetate (DMPA), 13.63% had undergone TL, 11.81% used barrier contraception, while 22.72% did not use any contraception in the focussed counseling group. In the routine counseling group, 16.36% of women inserted PPIUCD, 20% used injectable DMPA, 12.72% underwent TL, 18.18% used barrier contraception, and 32.72% did not use any contraception. Conclusion Although PPIUCD is a long-acting reversible contraceptive that is safe and reliable, only a few women choose it as a method of birth control. This may be due to ignorance, misconceptions, and worries/fears about potential difficulties/adverse effects associated with IUCD insertion. The IUCD stigma mostly results from misconceptions about the fear of complications. Hence, we recommend that proper IUCD counseling be provided during antenatal care visits to dispel misunderstandings and concerns regarding potential complications associated with PPIUCD insertion.
PubMed: 37456407
DOI: 10.7759/cureus.40344 -
International Journal of Molecular... Jun 2023Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled...
Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that levels are induced by medroxyprogesterone acetate (MPA) and etonogestrel (ETO) in cultured HESCs. We hypothesized that pLARC-induced ZBTB16 expression contributes to HESC decidualization, whereas prolonged enhancement of ZBTB16 levels triggers an inflammatory milieu by inducing pro-inflammatory gene expression and tissue-factor-mediated thrombin generation in decidualized HESCs. Thus, ZBTB16 immunostaining was performed in paired endometria from pre- and post-depo-MPA (DMPA)-administrated women and oophorectomized guinea pigs exposed to the vehicle, estradiol (E), MPA, or E + MPA. The effect of progestins including MPA, ETO, and levonorgestrel (LNG) and estradiol + MPA + cyclic-AMP (E + MPA + cAMP) on levels were measured in HESC cultures by qPCR and immunoblotting. The regulation of levels by MPA was evaluated in glucocorticoid-receptor-silenced HESC cultures. was overexpressed in cultured HESCs for 72 h followed by a ± 1 IU/mL thrombin treatment for 6 h. DMPA administration in women and MPA treatment in guinea pigs enhanced ZBTB16 immunostaining in endometrial stromal and glandular epithelial cells. The findings indicated that: (1) ZBTB16 levels were significantly elevated by all progestin treatments; (2) MPA exerted the greatest effect on levels; (3) MPA-induced expression was inhibited in glucocorticoid-receptor-silenced HESCs. Moreover, overexpression in HESCs significantly enhanced prolactin (), insulin-like growth factor binding protein 1 (), and tissue factor () levels. Thrombin-induced interleukin 8 ( and prostaglandin-endoperoxide synthase 2 ( mRNA levels in control-vector-transfected HESCs were further increased by overexpression. In conclusion, these results supported that ZBTB16 is enhanced during decidualization, and long-term induction of ZBTB16 expression by pLARCs contributes to thrombin generation through enhancing tissue factor expression and inflammation by enhancing and levels in decidualized HESCs.
Topics: Female; Humans; Animals; Guinea Pigs; Progestins; Interleukin-8; Thrombin; Contraceptive Agents; Thromboplastin; Glucocorticoids; Cyclooxygenase 2; Endometrium; Estradiol; Inflammation; Stromal Cells; Cells, Cultured; Decidua; Medroxyprogesterone Acetate
PubMed: 37445713
DOI: 10.3390/ijms241310532 -
PloS One 2023Women who use hormonal contraception face delayed return of fertility upon discontinuation. There was limited evidence of fertility return after hormonal contraceptive...
Fertility return after hormonal contraceptive discontinuation and associated factors among women attended Family Guidance Association of Ethiopia Dessie model clinic, Northeast Ethiopia: A cross-sectional study.
BACKGROUND
Women who use hormonal contraception face delayed return of fertility upon discontinuation. There was limited evidence of fertility return after hormonal contraceptive discontinuation in the study area. Hence this study assessed fertility return after hormonal contraceptive discontinuation and associated factors among pregnant women attending Family Guidance Association Ethiopia (FGAE) Dessie model clinic, Northeast Ethiopia, 2019.
METHODS
A cross-sectional study was conducted on 423 samples selected by using systematic random sampling. Data were collected by face-to-face interview using a pretested and structured questionnaire and reviewing client records. Data were entered using Epi Data version 3.1 and analyzed using SPSS version 23. Both bi-variable and multivariable binary logistic regressions were used to identify predictors of delayed fertility return. Adjusted odds ratio (AOR) along with a 95% Confidence Interval (CI) was used to measure the strength and the direction of the association and statistical significance was declared at a P-value less than 0.05.
RESULT
The proportion of fertility return among currently pregnant women after discontinuation of any hormonal contraceptive methods was 88.6% (95% CI; (85.6%-92%)). The proportion of fertility return among Depo-Provera, implant, Intrauterine Contraceptive Device (IUCD), and Oral Contraceptive Pill (OCP) users was 75%, 99.1%, 100%, and 97.8% respectively. Age, (AOR = 5.37, (95% CI; (1.48, 13.6)) and using Depo-Provera (AOR = 4.82, 95% CI; (1.89, 14.2)) had a significant association with delayed fertility return.
CONCLUSIONS
The proportion of fertility return among women after discontinuation of any hormonal contraceptive methods was high. Age and using Depo-Provera had a positive association with delayed fertility return. This study recommends a contraceptive counseling approach that addresses concerns about delay in the return of fertility after hormonal contraceptive discontinuation to avoid confusion among family planning users.
Topics: Pregnancy; Female; Humans; Cross-Sectional Studies; Ethiopia; Medroxyprogesterone Acetate; Fertility; Contraceptives, Oral; Intrauterine Devices
PubMed: 37432916
DOI: 10.1371/journal.pone.0287440 -
Systematic Reviews Jul 2023Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for... (Review)
Review
BACKGROUND
Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for improving contraceptive access, continuation, and autonomy. However, there are challenges in rolling out this new efficacious intervention, and major implementation problems have been encountered during scale-up.
OBJECTIVE
To describe the implementation strategies to scale up self-administered DMPA-SC and the barriers, facilitators, and outcomes of these programs.
METHOD
Recent guidelines, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, were used to design and report this review. An article or report was eligible for inclusion if it reported interventions that could scale up self-administered DMPA-SC implementation or its facilitators, barriers, or outcomes. We searched six electronic databases and the grey literature for eligible articles and reports. Two reviewers independently screened the document titles, abstracts, and full texts to identify eligible documents. Data were extracted using structured forms. Using the Effective Practice and Organization of Care (EPOC) taxonomy of health systems framework for thematic analysis, data were presented in a narrative approach.
RESULTS
Of the 755 retrieved documents, 34 were included in this review. Most of the documents included were multi-country reports (n = 14), and all documents were published within the last 5 years (2018-2021). This review identified documents that reported interventions in all EPOC domains. The most-reported interventions were: task-sharing amongst health workforce cadres, engaged leadership, encouraging policies, training and education, DMPA-SC demand generation, integration into existing programs, improved funding mechanisms, collaboration with development partners, and supply chain strengthening. The main barriers were suboptimal funding, inadequate human resources, and poor logistics supply of DMPA-SC. There was minimal evidence of scale-up outcomes.
CONCLUSION
This scoping review reported a wide range of interventions employed by countries and programs to scale up DMPA-SC self-administration but minimal evidence of the scale-up outcomes. Evidence from this review can help design better programs that improves access to quality family planning services to achieve the Sustainable Development Goals (SDG) targets 3.7. However, efforts should focus on rigorous implementation research that assess scaled up self-administered DMPA-SC interventions and report their outcomes.
REGISTRATION
The protocol for this review was registered in the protocols.io repository ( https://www.protocols.io/view/a-protocol-for-a-scoping-review-of-implementation-x54v9yemmg3e/v1 ).
Topics: Female; Humans; Contraception; Contraceptive Agents, Female; Injections, Subcutaneous; Medroxyprogesterone Acetate; Self Administration
PubMed: 37403147
DOI: 10.1186/s13643-023-02216-2 -
British Journal of Cancer Sep 2023The effectiveness of conservative treatment of endometrial carcinoma (EC) with oral progesterone therapy, such as medroxyprogesterone acetate (MPA), can be blunted due...
BACKGROUND
The effectiveness of conservative treatment of endometrial carcinoma (EC) with oral progesterone therapy, such as medroxyprogesterone acetate (MPA), can be blunted due to primary or acquired resistance, but the underlying mechanisms remain incompletely defined.
METHODS
Genome-wide CRISPR screening was performed to identify potential regulators in response to MPA in Ishikawa cells. Crystal violet staining, RT-qPCR, western blotting, ChIP-qPCR and luciferase assays were employed to elucidate the p53-AarF domain-containing kinase 3 (ADCK3) regulatory axis and its roles in sensitizing EC cells to MPA treatment.
RESULTS
ADCK3 is identified as a previously unrecognized regulator in response to MPA in EC cells. Loss of ADCK3 in EC cells markedly alleviated MPA-induced cell death. Mechanistically, loss of ADCK3 primarily suppresses MPA-mediated ferroptosis by abrogating arachidonate 15-lipoxygenase (ALOX15) transcriptional activation. Moreover, we validated ADCK3 as a direct downstream target of the tumor suppressor p53 in EC cells. By stimulating the p53-ADCK3 axis, the small-molecule compound Nutlin3A synergized with MPA to efficiently inhibit EC cell growth.
CONCLUSIONS
Our findings reveal ADCK3 as a key regulator of EC cells in response to MPA and shed light on a potential strategy for conservative EC treatment by activating the p53-ADCK3 axis to sensitize MPA-mediated cell death.
Topics: Female; Humans; Medroxyprogesterone Acetate; Tumor Suppressor Protein p53; Clustered Regularly Interspaced Short Palindromic Repeats; Endometrial Neoplasms; Cell Line, Tumor
PubMed: 37402867
DOI: 10.1038/s41416-023-02347-2 -
Cell Death Discovery Jun 2023Medroxyprogesterone (MPA) has therapeutic effect on endometrial carcinoma (EC), while it could promote the carcinogenesis of breast cancer (BC) by activating receptor...
Medroxyprogesterone (MPA) has therapeutic effect on endometrial carcinoma (EC), while it could promote the carcinogenesis of breast cancer (BC) by activating receptor activator of NF-kB ligand (RANKL). However, the selective mechanism of MPA in endometrium and breast tissue remains obscure. Multiomics analysis of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) were performed in cell lines derived from endometrial cancer and mammary tumor to screen the differential co-regulatory factors of progesterone receptor (PR). Dual-luciferase assays and ChIP-PCR assays were used to validate the transcriptional regulation. Co-immunoprecipitation (Co-IP) and immunofluorescence assays were carried out to explore molecular interactions between PR, the cofactor transcriptional repressor GATA binding 1 (TRPS1), and histone deacetylase 2 (HDAC2). Subsequently, human endometrial cancer/breast cancer xenograft models were established to investigate the regulation effect of cofactor TRPS1 in vivo. In the current study, we found that MPA downregulated RANKL expression in a time- and dose-dependent manner in EC, while had the opposite effect on BC. Then PR could recruit cofactor TRPS1 to the promoter of RANKL, leading to histone deacetylation of RANKL to repress its transcription in EC, whereas MPA disassociated the PR/TRPS1/HDAC2 complex to enhance RANKL histone acetylation in BC. Therefore, TRPS1, the coregulator recruited by PR played a critical role in the selective mechanism of progesterone in EC and BC and could become a potential candidate for targeted therapy to improve the anticancer effect of MPA on EC and avoid its carcinogenic effect on BC.
PubMed: 37344459
DOI: 10.1038/s41420-023-01484-0 -
Journal For Immunotherapy of Cancer Jun 2023Progress in breast cancer (BC) research relies on the availability of suitable cell lines that can be implanted in immunocompetent laboratory mice. The best studied...
BACKGROUND
Progress in breast cancer (BC) research relies on the availability of suitable cell lines that can be implanted in immunocompetent laboratory mice. The best studied mouse strain, C57BL/6, is also the only one for which multiple genetic variants are available to facilitate the exploration of the cancer-immunity dialog. Driven by the fact that no hormone receptor-positive (HR) C57BL/6-derived mammary carcinoma cell lines are available, we decided to establish such cell lines.
METHODS
BC was induced in female C57BL/6 mice using a synthetic progesterone analog (medroxyprogesterone acetate, MPA) combined with a DNA damaging agent (7,12-dimethylbenz[a]anthracene, DMBA). Cell lines were established from these tumors and selected for dual (estrogen+progesterone) receptor positivity, as well as transplantability into C57BL/6 immunocompetent females.
RESULTS
One cell line, which we called B6BC, fulfilled these criteria and allowed for the establishment of invasive estrogen receptor-positive (ER) tumors with features of epithelial to mesenchymal transition that were abundantly infiltrated by myeloid immune populations but scarcely by T lymphocytes, as determined by single-nucleus RNA sequencing and high-dimensional leukocyte profiling. Such tumors failed to respond to programmed cell death-1 (PD-1) blockade, but reduced their growth on treatment with ER antagonists, as well as with anthracycline-based chemotherapy, which was not influenced by T-cell depletion. Moreover, B6BC-derived tumors reduced their growth on CD11b blockade, indicating tumor sustainment by myeloid cells. The immune environment and treatment responses recapitulated by B6BC-derived tumors diverged from those of ER TS/A cell-derived tumors in BALB/C mice, and of ER E0771 cell-derived and MPA/DMBA-induced tumors in C57BL/6 mice.
CONCLUSIONS
B6BC is the first transplantable HR BC cell line derived from C57BL/6 mice and B6BC-derived tumors recapitulate the complex tumor microenvironment of locally advanced HR BC naturally resistant to PD-1 immunotherapy.
Topics: Mice; Female; Animals; Progesterone; Epithelial-Mesenchymal Transition; Mice, Inbred BALB C; Mice, Inbred C57BL; Cell Line, Tumor; Carcinoma; Tumor Microenvironment
PubMed: 37344100
DOI: 10.1136/jitc-2023-007117 -
Current HIV/AIDS Reports Aug 2023The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although... (Review)
Review
PURPOSE OF REVIEW
The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although DMPA-IM provides reliable contraception, potential effects on the female genital tract (FGT) mucosa have raised concern, including risk of HIV infection. This review summarises and compares evidence from observational cohort studies and the randomised Evidence for Contraceptive Options in HIV Outcomes (ECHO) Trial.
RECENT FINDINGS
Although previous observational studies found women using DMPA-IM had higher abundance of bacterial vaginosis (BV)-associated bacteria, increased inflammation, increased cervicovaginal HIV target cell density, and epithelial barrier damage, sub-studies of the ECHO Trial found no adverse changes in vaginal microbiome, inflammation, proteome, transcriptome, and risk of viral and bacterial STIs, other than an increase in Th17-like cells. Randomised data suggest that DMPA-IM use does not adversely change mucosal endpoints associated with acquisition of infections. These findings support the safe use of DMPA-IM in women at high risk of acquiring STIs, including HIV.
Topics: Female; Humans; Medroxyprogesterone Acetate; Contraceptive Agents, Female; HIV Infections; Bacteria; Inflammation; Mucous Membrane; Observational Studies as Topic
PubMed: 37341916
DOI: 10.1007/s11904-023-00662-0