Non-hormonal Contraception Research Articles

IS CONTRACEPTIVE INJECTION CAUSE BREAST CANCER? : META ANALYSIS

Background: Injectable hormonal contraception was a major risk factor for breast cancer. The content of the progestin hormone in injection hormonal contraceptives can affect the uncontrolled growth of breast tissue, leading to breast cancer. This study aims to analyze the magnitude of the effect of injection hormonal contraception on the incidence of breast cancer with a meta-analysis study. Method: This research is a systematic review and used a Prisma flow diagram. The process of searching for articles through a database of journals which includes: PubMed, Science Direct, and Google Scholar by selecting articles published in 2010-2020. Keywords used include: “ Women Aged 15-80 Years” OR “Women of Menopause” AND “Birth control injections” AND “Breast Cancer”. The inclusion criteria included full-text articles with a case-control study design, articles using English, and multivariate analysis with adjusted odds ratios. Artikel fulfills the requirements for analysis using Revman 5.3 Result: There were 6 articles with the case-control study. A meta-analysis of 6 case-control studies showed that the use of injectable hormonal contraception had a 1.37 times risk of developing breast cancer compared with women using non-hormonal contraception (aOR 1.37; 95% CI 1.09 to 1.71; p = 0.006). Conclusion: Injectable hormonal contraceptives can increase the incidence of breast cancer.

P063Association between postpartum contraceptive use and postpartum depression at 12 months

<h3>Objectives</h3> To evaluate whether progestin-only (POC) or combined hormonal contraception (CHC) users are more likely to have a positive 12-month postpartum depression screen compared with those using non-hormonal (NH) or no contraception. <h3>Methods</h3> We conducted a secondary analysis of a prospective cohort of pregnant patients followed for one year postpartum. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) in the second or third trimester and 12 months post-delivery. We examined differences in participant characteristics, mental health history, and 12-month EPDS scores between method groups: POC, CHC, and NH contraception or no contraception. We used multivariable logistic regression to assess factors associated with positive depression screen (EPDS ≥10) at 12 months, adjusting for differences between groups and contraceptive discontinuation. <h3>Results</h3> Of the 227 participants in this analysis, 47% chose POC, 19% chose CHC, and 34% chose NH or no contraception. The overall incidence of positive depression screen at 12 months was 21.2% and did not differ by contraceptive method: POC, 18.7%; CHC, 28.6%; and no method/NH 20.5% (p=0.39). After adjusting for confounders, contraceptive method remained unassociated with depression (POC adjusted OR (aOR), 0.59; 95% CI, 0.28–1.40; CHC aOR, 1.38; 95% CI, 0.53–3.58). However, last antenatal EPDS score ≥10 (aOR, 5.88; 95% CI, 2.5413.59) and postpartum mental health referral (aOR, 3.81; 95% CI, 1.94–7.49) were significantly associated. <h3>Conclusions</h3> In this cohort, the incidence of postpartum depression was greater than 20%. Individuals initiating hormonal contraception in the first 12 months postpartum were no more likely to have a positive depression screen at 12 months postpartum.

Testis-specific serine kinase 3 is required for sperm morphogenesis and male fertility.

The importance of phosphorylation in sperm during spermatogenesis has not been pursued extensively. Testis-specific serine kinase 3 (Tssk3) is a conserved gene, but TSSK3 kinase functions and phosphorylation substrates of TSSK3 are not known. The goals of our studies were to understand the mechanism of action of TSSK3. We analyzed the localization of TSSK3 in sperm, used CRISPR/Cas9 to generate Tssk3 knockout (KO) mice in which nearly all of the Tssk3 open reading frame was deleted (ensuring it is a null mutation), analyzed the fertility of Tssk3 KO mice by breeding mice for 4 months, and conducted phosphoproteomics analysis of male testicular germ cells. TSSK3 is expressed in elongating sperm and localizes to the sperm tail. To define the essential roles of TSSK3 in vivo, heterozygous (HET) or homozygous KO male mice were mated with wild-type females, and fertility was assessed over 4 months; Tssk3 KO males are sterile, whereas HET males produced normal litter sizes. The absence of TSSK3 results in disorganization of all stages of testicular seminiferous epithelium and significantly increased vacuolization of germ cells, leading to dramatically reduced sperm counts and abnormal sperm morphology; despite these histologic changes, Tssk3 null mice have normal testis size. To elucidate the mechanisms causing the KO phenotype, we conducted phosphoproteomics using purified germ cells from Tssk3 HET and KO testes. We found that proteins implicated in male infertility, such as GAPDHS, ACTL7A, ACTL9, and REEP6, showed significantly reduced phosphorylation in KO testes compared to HET testes, despite unaltered total protein levels. We demonstrated that TSSK3 is essential for male fertility and crucial for phosphorylation of multiple infertility-related proteins. These studies and the pathways in which TSSK3 functions have implications for human male infertility and nonhormonal contraception.

Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates.

Soluble adenylyl cyclase (sAC: ADCY10) is an enzyme involved in intracellular signaling. Inhibition of sAC has potential therapeutic utility in a number of areas. For example, sAC is integral to successful male fertility: sAC activation is required for sperm motility and ability to undergo the acrosome reaction, two processes central to oocyte fertilization. Pharmacologic evaluation of existing sAC inhibitors for utility as on-demand, nonhormonal male contraceptives suggested that both high intrinsic potency, fast on and slow dissociation rates are essential design elements for successful male contraceptive applications. During the course of the medicinal chemistry campaign described here, we identified sAC inhibitors that fulfill these criteria and are suitable for in vivo evaluation of diverse sAC pharmacology.

Multipurpose vaginal rings for HIV prevention and non-hormonal contraception

Vaginal rings releasing antiretrovirals - either alone or in combination with contraceptive progestins - are being developed for contraception and prevention of human immunodeficiency virus (HIV) transmission via vagina. However, hormonal contraceptives are associated with numerous side effects and contraindications, and many women are interested in using hormone-free contraceptives. The aim of this project is to develop multipurpose vaginal rings to release copper and/or zinc ions and dapivirine over a month for contraception and HIV prevention. Ring manufacture, swell testing, and in vitro drug release testing have been conducted. The experimental results obtained currently are encouraging and support the continued development of these ring formulations as a novel and interesting multipurpose prevention technology strategy.

Hubungan Karakteristik Wanita Usia Subur (WUS) dengan Penyakit Kanker Serviks

This study aims to determine the relationship between the quality of women of childbearing age (WUS) based on age, education, occupation, parity, and history of contraceptive use with cervical cancer growth. This research method is analytically observational with a case-control study design. The results of univariate analysis of 118 respondents aged&gt;35 years were 71 people (60.2%), high school education level was 47 people (39.8%), work as housewives (IRT) was 35 people (29.7% ), respondents with parity as many as 65 people (55.1%) and the use of non-hormonal contraception as many as 56 people (47.5%). The results of this study found that there was a significant relationship between age, occupation, and parity (α=&lt;0.05). In contrast, employment and history of contraceptive use did not show any association with cervical cancer (α&gt;0.05). The results of data analysis with the chi-square test got a value of 0.025 or p &lt;α (0.05). In conclusion, there is a significant relationship between age, occupation, and parity with cervical cancer.&#x0D; &#x0D; Keywords: Cervical Cancer, Women of Childbearing Age

Australian fertility preservation guidelines for people with cancer 2022: review and recommendations.

Australian fertility preservation guidelines for people with cancer 2022: review and recommendations.

G-Protein Coupled Receptors in Human Sperm: An In Silico Approach to Identify Potential Modulatory Targets.

G protein-coupled receptors (GPCRs) are involved in several physiological processes, and they represent the largest family of drug targets to date. However, the presence and function of these receptors are poorly described in human spermatozoa. Here, we aimed to identify and characterize the GPCRs present in human spermatozoa and perform an in silico analysis to understand their potential role in sperm functions. The human sperm proteome, including proteomic studies in which the criteria used for protein identification was set as <5% FDR and a minimum of 2 peptides match per protein, was crossed with the list of GPCRs retrieved from GLASS and GPCRdb databases. A total of 71 GPCRs were identified in human spermatozoa, of which 7 had selective expression in male tissues (epididymis, seminal vesicles, and testis), and 9 were associated with male infertility defects in mice. Additionally, ADRA2A, AGTR1, AGTR2, FZD3, and GLP1R were already associated with sperm-specific functions such as sperm capacitation, acrosome reaction, and motility, representing potential targets to modulate and improve sperm function. Finally, the protein-protein interaction network for the human sperm GPCRs revealed that 24 GPCRs interact with 49 proteins involved in crucial processes for sperm formation, maturation, and fertilization. This approach allowed the identification of 8 relevant GPCRs (ADGRE5, ADGRL2, GLP1R, AGTR2, CELSR2, FZD3, CELSR3, and GABBR1) present in human spermatozoa that can be the subject of further investigation to be used even as potential modulatory targets to treat male infertility or to develop new non-hormonal male contraceptives.

Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential.

In mammalian cells, 10 different adenylyl cyclases produce the ubiquitous second messenger, cyclic adenosine monophosphate (cAMP). Amongst these cAMP-generating enzymes, bicarbonate (HCO3 −)-regulated soluble adenylyl cyclase (sAC; ADCY10) is uniquely essential in sperm for reproduction. For this reason, sAC has been proposed as a potential therapeutic target for non-hormonal contraceptives for men. Here, we describe key sAC-focused in vitro assays to identify and characterize sAC inhibitors for therapeutic use. The affinity and binding kinetics of an inhibitor can greatly influence in vivo efficacy, therefore, we developed improved assays for assessing these efficacy defining features.

Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide

The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b5 (Twcytb5-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.

Predictors of Depressive Symptoms in Postpartum Women: The Role of Contraceptive Use, Type and Health-Related Factors

Background: The postpartum period is critical for women due to significant bio-psychosocial changes and the consequences of delivery.&#x0D; Aims: The purpose of this study was to investigate the role of the use of contraceptives and other health-related factors in the risk of developing postpartum depression among women in Jordan.&#x0D; Materials and methods: A cross-sectional, descriptive-correlational design was used to recruit 803 women using a convenience sample technique from the central district of Jordan. Data were collected on depressive symptoms, contraceptive use and type, and pregnancy health-related factors. &#x0D; Results: Using binary logistic regression analysis, non-hormonal contraceptives and musculoskeletal pain were significant predictors (p&lt;.05) of the risk of developing depressive symptoms in the sampled women (OR=4.1, 3.8; respectively). For the women in our sample, 24.9% (n=200) developed depressive symptoms. Most of those who felt depressed reported suffering from insomnia (50.0%] and baby blues (13.0%), while loss of appetite was reported by 33.0%. The analysis also showed that 51.0% (n=409) had used at least one method of contraception. Among those using contraceptive methods, 31.0% had only used hormonal contraceptives compared to 69.0% using non-hormonal forms.&#x0D; Conclusion: Non-hormonal contraceptive use and musculoskeletal pain were found to be significantly associated with the risk of developing postpartum depressive symptoms. Family and reproductive health professionals need to emphasize the bio-psychological aspects of health for pregnant and postpartum women.

Hormonal Contraception Use and Depression Among Women in Saudi Arabia.

PurposeTo estimate the prevalence of depression amongst hormonal and non-hormonal contraception users, and the risk factors associated with depression in the sample.Patients and MethodsThis is a community-based cross-sectional study conducted in the Kingdom of Saudi Arabia from October to November 2021, covering all regions of Saudi Arabia. All participants were women, living in Saudi Arabia, ≥21 years old and ≤45 years old, using a contraceptive method, and with no established history of depression.ResultsA total of 4853 out of 18,596 met our criteria and were included in this study. Among all sample groups, 29% had moderate to severe depression. Rates of depression and association studies’ results in women using hormonal were higher than those who use non-hormonal birth control methods. Psychiatric disorders, medical illnesses, substance use and depressogenic medication use were all associated with depression in both hormonal and non-hormonal contraception users.ConclusionThe current study shows high prevalence of depression amongst hormonal contraceptive users compared to non-hormonal contraceptive users.

The effects of hormonal contraceptive use on sleep patterns in women of reproductive age

PurposeHormonal contraceptives alter hormone levels in women and have been linked to alterations in sleep patterns; however, previous studies yielded inconsistent results and lacked generalizability. This study examines hormonal contraceptive use and its impact on sleep outcomes, including sleep duration and sleep disturbances. MethodsWomen self-reported their sleep patterns and use of contraceptives in the 2017 population-based Behavioral Risk Factor Surveillance System Survey (n=1,970). Participants were categorized by use of hormonal or non-hormonal contraceptives for the purpose of pregnancy prevention. Sleep duration was defined as having met the recommended sleep levels of 7-9 hours per 24 hours. Sleep disturbances were defined as trouble falling asleep, staying asleep, or sleeping too much ≥ 6 days within a 14-day period. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated to examine the association between contraceptive use and each sleep outcome. SAS-callable SUDAAN was used for analyses to account for the complex sampling design. ResultsWomen who used hormonal contraceptives had 6% higher prevalence of sleep disturbances (PR: 1.06, 95% CI: 0.99, 1.14) and 17% lower prevalence of not meeting sleep duration recommendations (PR: 0.83, 95% CI: 0.71, 0.98) compared to those who used non-hormonal contraceptives after adjustment for age. ConclusionThese findings suggest the use of hormonal contraceptives may have negative impacts on sleep disturbances, and positive effects on sleep duration among women using contraceptives for preventing pregnancy. Future studies should be conducted in diverse populations utilizing objective measurements of sleep patterns.

O-293 The GnRH-agonist trigger alone can be used for egg maturation in altruistic egg donors using long-acting reversible contraceptives without compromising the outcome

Abstract Study question Does use of long-acting reversible contraceptives (LARC) compromise the efficacy of a GnRH agonist trigger in egg donors? Summary answer Using a GnRH-agonist trigger in altruistic egg donors using LARCs does not appear to compromise oocyte yield or maturity. What is known already GnRH-agonist triggers are recommended for altruistic egg donors to reduce the risk of ovarian hyperstimulation syndrome (OHSS) as any impact on the luteal phase would be clinically irrelevant. There is increasing usage of LARCs by young women due to their convenience and side-effect profile. A recent British Fertility Society survey (Mascarenhas et. al., 2021) indicated that many clinicians recommend removal before starting ovarian stimulation which incurs inconvenience to the donors and also risks unintended pregnancy. We had previously confirmed that women with LARC would respond to a GnRH-agonist trigger with an LH release deemed sufficient to induce oocyte maturation. Study design, size, duration Electronic records of 56 altruistic egg donation cycles with a GnRH-agonist trigger between January 2017 and December 2021 were retrospectively analysed. Of these, 38 were not on contraception or using non-hormonal contraceptive methods (Nil group), five were using oral contraception (Pill group), nine had a copper or levonorgesterol intrauterine device in situ (IUCD group) and four had a LARC in situ (LARC group). Participants/materials, setting, methods All stimulation involved GnRH-antagonist control. Donors with IUCDs or LARCs in situ were advised they could continue on their choice of contraception throughout the egg donation process. Oocyte retrieval was performed 36-37 hours post-GnRH-agonist trigger. The number of oocytes retrieved and the number of mature oocytes were recorded. As the numbers were small, the data is presented as median and interquartile range (IQR) and, given the small numbers, statistical analyses were expectedly, not significantly different. Main results and the role of chance The median age and AMH of the Nil group was 27.2 (IQR 25.4-29.3) years and 41.0 (IQR 33.0-65.3) pmol/L, for the IUCD group was 28.8 (IQR 24.8-29.3) years and 45.0 (IQR 38.0-54.0) pmol/L, and for the Pill group was 26.0 (IQR 24.0-27.2) years and 36.0 (31.0-40.0) pmol/L. Women in the LARC group were younger than in the nil group with a median age of 23.3 (IQR 22.6-23.6) (p = 0.016), but with no significant difference in the AMH levels 32.6 (IQR 22.8-40.5) pmol/L. There was no difference apparent in the number of oocytes retrieved between the groups: Nil group = 18.5 (IQR 12-24); Pill group = 21 (IQR 21-23); IUCD group = 19 (IQR 18-20); LARC group = 23 (IQR 11-33). The number of mature oocytes also appeared similar: Nil group = 14 (IQR 9-22); Pill group = 19 (IQR 17-20); IUCD group = 17 (IQR 15-18); LARC group = 19 (IQR 11-26). The oocyte maturity rates were also similar: Nil group = 86%; Pill group = 83%; IUCD group = 89%; LARC group = 78%. Limitations, reasons for caution A retrospective cohort study carries inherent disadvantages of confounding variables or variation in baseline characteristics as compared with a randomised controlled trial. The low sample size would have meant that results of any statistical analysis runs the risk of being insignificant or spurious which we have therefore deliberately refrained from. Wider implications of the findings Although derived from a small sample size, the finding that the GnRH-trigger alone can be deployed in women using LARCs without compromising egg numbers or maturity can give clinicians confidence to perform GnRH-agonist triggering for altruistic egg donors or others wishing to store eggs or embryos, thus maximising patient safety. Trial registration number Not applicable

Discovery and Characterization of Multiple Classes of Human CatSper Blockers.

The cation channel of sperm (CatSper) is a validated target for nonhormonal male contraception, but it lacks selective blockers, hindering studies to establish its role in both motility and capacitation. Via an innovative calcium uptake assay utilizing human sperm we discovered novel inhibitors of CatSper function from a high‐throughput screening campaign of 72,000 compounds. Preliminary SAR was established for seven hit series. HTS hits or their more potent analogs blocked potassium‐induced depolarization and noncompetitively inhibited progesterone‐induced CatSper activation. CatSper channel blockade was confirmed by patch clamp electrophysiology and these compounds inhibited progesterone‐ and prostaglandin E1‐induced hyperactivated sperm motility. One of the hit compounds is a potent CatSper inhibitor with high selectivity for CatSper over hCav1.2, hNav1.5, moderate selectivity over hSlo3 and hERG, and low cytotoxicity and is therefore the most promising inhibitor identified in this study. These new CatSper blockers serve as useful starting points for chemical probe development and drug discovery efforts.

Contraception utilization in women with pregestational diabetes

Objective To compare contraception use between women with and without pregestational diabetes. Methods Cross-sectional data on women aged 18–44 years from 2011 to 2017 National Survey of Family Growth (NSFG) was analysed. Maternal diabetes was defined as the presence of pre-gestational type 1 or type 2 diabetes. Bivariate and multiple logistic regression analyses were run to evaluate the association between the use of contraception and by contraception type: permanent, long-acting reversible contraception (LARC), other hormonal method, other non-hormonal method, and none, and maternal diabetes status, controlling for relevant covariates. Results Among the total study sample of 28,454, 1344 (4.7%) had pregestational diabetes. Unadjusted analysis showed women with a history of pregestational diabetes were more likely to use permanent contraception following pregnancy (58.0% vs. 38.7%, p < 0.001) or no contraception (27.2% vs. 24.5%, p < 0.001), but less likely to use LARC (3.4% vs. 11.7%, p < 0.001), other hormonal contraception (4.1% vs. 8.9%, p < 0.001), or other non-hormonal contraception (7.2% vs. 16.4%, p < 0.001). In adjusted analyses, permanent (aOR 1.62, 95% CI 0.72–2.26) remained significant, however the differences were no longer statistically significant: LARC (aOR 0.34, 95% CI 0.12–1.00); other hormonal (aOR 0.61, 95% CI 0.27–1.35); other non-hormonal (aOR 0.59, 95% CI 0.25–1.43); and None (aOR 1.11, 95% CI 0.65–1.89). Conclusion In this analysis, we found that women with pregestational diabetes were more likely to use permanent contraception methods compared to women without pregestational diabetes; however over a quarter of women with pregestational diabetes did not use contraception between pregnancies.

Contraception

Most individuals will wish to avoid pregnancy for some part of their reproductive years. A variety of hormonal and nonhormonal contraceptive methods are available, which have different characteristics related to systemic effects, bleeding patterns, and effort required on the user’s part. The goal of contraceptive counseling is to identify a method that is safe and compatible with the individual’s preferences. Clinicians may often be able to help patients initiate contraception on the day of the initial office visit. They should remain available and supportive to patients who wish to switch methods and provide comprehensive counseling for all available contraceptive methods as well as emergency contraception options. This review contains 8 figures, 7 tables and 51 references Keywords: birth control, contraception, emergency contraception, Essure, hysteroscopy, interval, laparoscopy, microinserts, postpartum, salpingectomy, sterilization

Contraception

Most individuals will wish to avoid pregnancy for some part of their reproductive years. A variety of hormonal and nonhormonal contraceptive methods are available, which have different characteristics related to systemic effects, bleeding patterns, and effort required on the user’s part. The goal of contraceptive counseling is to identify a method that is safe and compatible with the individual’s preferences. Clinicians may often be able to help patients initiate contraception on the day of the initial office visit. They should remain available and supportive to patients who wish to switch methods and provide comprehensive counseling for all available contraceptive methods as well as emergency contraception options. This review contains 8 figures, 7 tables and 51 references Keywords: birth control, contraception, emergency contraception, Essure, hysteroscopy, interval, laparoscopy, microinserts, postpartum, salpingectomy, sterilization

Contraception

Most individuals will wish to avoid pregnancy for some part of their reproductive years. A variety of hormonal and nonhormonal contraceptive methods are available, which have different characteristics related to systemic effects, bleeding patterns, and effort required on the user’s part. The goal of contraceptive counseling is to identify a method that is safe and compatible with the individual’s preferences. Clinicians may often be able to help patients initiate contraception on the day of the initial office visit. They should remain available and supportive to patients who wish to switch methods and provide comprehensive counseling for all available contraceptive methods as well as emergency contraception options. This review contains 8 figures, 7 tables and 51 references Keywords: birth control, contraception, emergency contraception, Essure, hysteroscopy, interval, laparoscopy, microinserts, postpartum, salpingectomy, sterilization

Contraception

Most individuals will wish to avoid pregnancy for some part of their reproductive years. A variety of hormonal and nonhormonal contraceptive methods are available, which have different characteristics related to systemic effects, bleeding patterns, and effort required on the user’s part. The goal of contraceptive counseling is to identify a method that is safe and compatible with the individual’s preferences. Clinicians may often be able to help patients initiate contraception on the day of the initial office visit. They should remain available and supportive to patients who wish to switch methods and provide comprehensive counseling for all available contraceptive methods as well as emergency contraception options. This review contains 8 figures, 7 tables and 51 references Keywords: birth control, contraception, emergency contraception, Essure, hysteroscopy, interval, laparoscopy, microinserts, postpartum, salpingectomy, sterilization