Combined Oral Contraceptives Research Articles

Current oral contraceptive use affects explicit and implicit measures of depression in women.

Some data suggest that increased depressive symptoms may occur in women using combined oral contraceptives (OCs). However, this idea is controversial and the existing evidence is conflicting. The present study compared negative affect in 53 healthy women (M age = 19.9 years) during intervals of active daily OC hormone intake and during the washout week of the contraceptive cycle when no exogenous estrogens or progestins are used. A prospective counterbalanced repeated-measures study design was employed. Depressive affect was evaluated using standard psychometric tests of explicit (self-perceived) and implicit negative affect. Implicit measures are considered less subject to bias related to social expectations, self-awareness, or willingness to disclose. Other than their usual OCs, participants were medication-free and had been using OCs for a median of 12 mo. We found that measures of implicit affect (e.g., Affect Misattribution Procedure, Emotional Stroop Test) displayed a more depressive-like pattern of performance during active hormone intake, particularly among a subgroup of OC users who reported experiencing high levels of depressive affect more generally. In contrast, participants' self-perceptions suggested that they perceived their negative symptoms to be greater during the 'off' phase of the OC cycle, when OC steroids are withdrawn and menses occurs. The present findings reinforce the possibility of depressive mood effects associated with OC usage, and highlight the utility of including implicit measures, but also illustrate the complexity of mood assessment in OC users.

12539 Estrogen Type In Contraceptives Matters: Effects On Spatial Memory And Anxiety-Like Behaviors In A Female Rat Model

Abstract Disclosure: A.P. Hegwood: None. S. Kujawa: None. A.V. Prakapenka: None. According to U.S. Centers for Disease Control & Prevention, ∼12% of the U.S. population uses combined oral contraceptives (COCs). Behavioral side effects are common factors in COC discontinuation. Management of COC-related side effects primarily centers around altering the synthetic ethinyl estradiol (EE) dose, the predominant estrogen in COCs. Estradiol valerate (EV) is a recently introduced natural estrogen alternative to EE. EE-containing COCs, such as EE/dienogest (DNG), were found to decrease free steroid hormone serum levels compared to EV-containing COCs, such as EV/DNG. In women and in female rodent models, steroid hormones (e.g., 17-ß estradiol (E2), testosterone) dose-dependently modulate spatial memory and anxiety-related behaviors. We hypothesized that in a rat model of hormonal contraceptive use, EE/DNG differentially modulates spatial memory and anxiety-like behaviors compared to EV/DNG, corresponding to circulating steroid hormone levels. Thirty-six young-adult (3-4-months-old) female rats were randomly assigned to EE/DNG (0.13µg EE and 8.6µg DNG per day), EV/DNG (8.6µg EV and 8.6µg DNG per day), or vehicle treatment (propylene glycol) continuously administered by subcutaneous osmotic pump. At four weeks of treatment, rats were tested on the delayed spontaneous alternation (dSA) task to evaluate spatial memory and the elevated plus maze (EPM) to evaluate anxiety-like behavior. Following EPM, serum was collected and analyzed for E2, progesterone, androstenedione, and testosterone levels using liquid chromatography-mass spectrometry and corticosterone levels using radioimmunoassay. Spontaneous alternation behaviors were similar across all three groups on the dSA. However, EE/DNG increased use of an egocentric navigational strategy, the use of consecutive turns, on the dSA compared to vehicle and EV/DNG. Egocentric strategy is likely mediated by the striatal memory system, engagement of which is elevated with stress and anxiety. Of note, EE/DNG decreased time spent in the open arms of the EPM compared to vehicle and EV/DNG, indicating increased anxiety-like behaviors with EE/DNG. Both EE/DNG and EV/DNG decreased androstenedione, testosterone, and E2 circulating levels compared to vehicle. Steroid hormone serum levels did not differ between EE/DNG and EV/DNG; 58% of EE/DNG serum samples were undetermined/below threshold for E2 levels, limiting statistical analysis. Altogether, we found that, compared to vehicle and the natural EV, the synthetic EE component in hormonal contraceptives elevates anxiety-like behaviors in female rats, an effect that corresponds to increased use of an egocentric navigational strategy on a spatial memory task. Our findings support the notion that estrogen type matters for behavioral outcomes associated with contraceptive use, identifying estrogen type as a possible tool for management of COC-related side effects. Presentation: 6/1/2024

12413 Reversal Of Congenital Hypogonadotropic Hypogonadism (CHH) In A Woman With A Heterozygous Inactivating Variant In GnRHR Gene

Abstract Disclosure: S.W. Nyunt: None. M. Phylactou: None. K. Koysombat: None. J. Tsoutsouki: None. A.C. Yeung: None. M. Young: None. A. Newman: None. A.N. Comninos: None. Y. Mamoojee: None. N. Pitteloud: None. R. Quinton: None. W.S. Dhillo: None. A. Abbara: None. Introduction: Congenital Hypogonadotropic Hypogonadism (CHH) is a rare genetic condition with central hypogonadism and pubertal failure affecting both sexes. Reversal of CHH is far less commonly reported in women in the literature. We presented a case of reversal of CHH in a woman with heterozygous GnRHR mutation and the use of kisspeptin in interrogating hypothalamic function. Case history: Our patient presented with primary amenorrhea and incomplete puberty aged 15 yrs. Based on high BMI from early adolescence, clinical hyperandrogenism, family history of polycystic ovary syndrome (PCOS) and insulin resistance, she was diagnosed with PCOS and commenced on a combined oral contraceptive (COC), achieving breast development.Aged 21yrs, she was reassessed for amenorrhea off COC. Biochemical assessment revealed hypogonadotropic hypogonadism (HH): LH 0.2 IU/L, FSH 0.3 IU/L, estradiol <92 pmol/L. She had a normal sense of smell and Tanner 4 breasts; MRI demonstrated normal olfactory bulbs and pituitary. The diagnosis was therefore revised to CHH and COC was restarted, later changed to HRT due to hypertension. A 22-gene CHH panel (R148) identified a heterozygous pathogenic variant c.3171>Gp in GNRHR.At reassessment off HRT aged 32yrs, she remained amenorrheic. Ultrasound showed normal ovarian morphology, antral follicle counts 17 and endometrial thickness 5.8mm; hormonal assays: LH 5.0 IU/L, FSH 8.3 U/L, estradiol 162 pmol/L, AMH 12.2 pmol/L, testosterone 1.6 nmol/L (RR <2.0), SHBG 35 nmol/L (RR 30-100 nmol/L).She then achieved 20kg weight loss (BMI 41.8 to 35.2 kg/m2) on GLP-1 agonist. GnRH test (Gonadorelin 100mcg) incremented LH from 5.16 to 44.46 IU/L and FSH from 6.47 to 15.27 IU/L at 60 mins. After an intravenous kisspeptin (9.6nmol/kg) bolus, LH rose from 5.05 to 29.99 IU/L, FSH from 6.68 to 13.91 IU/L. Off HRT, she began having regular cycles (estradiol 800 pmol/L). Discussion: CHH was diagnosed based on primary amenorrhea, HH and pathogenic GnRHR variant that would not, however, be expected to result in a productive phenotype in the absence of a second deleterious allele (oligogenicity occurs in 20% of CHH), so whole exome sequencing is awaited. Kisspeptin is a potent stimulator of hypothalamic GnRH neurons and can be used to interrogate hypothalamic function. Typically, gonadotrophin responses to kisspeptin are minimal in CHH. Thus, her kisspeptin response was not consistent with CHH at time of assessment, indicating reversal of CHH (seen in 20% of CHH, particularly with GnRHR variants). Notably, her kisspeptin response was higher than in healthy women, consistent with decreased hypothalamic function and potentially a ‘Female Obesity-Related Hypogonadism’. Our case highlights the value of interrogating hypothalamic function using kisspeptin, both for the diagnosis of CHH, and to identify alternate pathology, as well as to identify recovery of reproductive function in CHH reversal. Presentation: 6/1/2024

12413 Reversal Of Congenital Hypogonadotropic Hypogonadism (CHH) In A Woman With A Heterozygous Inactivating Variant In GnRHR Gene

Abstract Disclosure: S.W. Nyunt: None. M. Phylactou: None. K. Koysombat: None. J. Tsoutsouki: None. A.C. Yeung: None. M. Young: None. A. Newman: None. A.N. Comninos: None. Y. Mamoojee: None. N. Pitteloud: None. R. Quinton: None. W.S. Dhillo: None. A. Abbara: None. Introduction: Congenital Hypogonadotropic Hypogonadism (CHH) is a rare genetic condition with central hypogonadism and pubertal failure affecting both sexes. Reversal of CHH is far less commonly reported in women in the literature. We presented a case of reversal of CHH in a woman with heterozygous GnRHR mutation and the use of kisspeptin in interrogating hypothalamic function. Case history: Our patient presented with primary amenorrhea and incomplete puberty aged 15 yrs. Based on high BMI from early adolescence, clinical hyperandrogenism, family history of polycystic ovary syndrome (PCOS) and insulin resistance, she was diagnosed with PCOS and commenced on a combined oral contraceptive (COC), achieving breast development.Aged 21yrs, she was reassessed for amenorrhea off COC. Biochemical assessment revealed hypogonadotropic hypogonadism (HH): LH 0.2 IU/L, FSH 0.3 IU/L, estradiol <92 pmol/L. She had a normal sense of smell and Tanner 4 breasts; MRI demonstrated normal olfactory bulbs and pituitary. The diagnosis was therefore revised to CHH and COC was restarted, later changed to HRT due to hypertension. A 22-gene CHH panel (R148) identified a heterozygous pathogenic variant c.3171>Gp in GNRHR.At reassessment off HRT aged 32yrs, she remained amenorrheic. Ultrasound showed normal ovarian morphology, antral follicle counts 17 and endometrial thickness 5.8mm; hormonal assays: LH 5.0 IU/L, FSH 8.3 U/L, estradiol 162 pmol/L, AMH 12.2 pmol/L, testosterone 1.6 nmol/L (RR <2.0), SHBG 35 nmol/L (RR 30-100 nmol/L).She then achieved 20kg weight loss (BMI 41.8 to 35.2 kg/m2) on GLP-1 agonist. GnRH test (Gonadorelin 100mcg) incremented LH from 5.16 to 44.46 IU/L and FSH from 6.47 to 15.27 IU/L at 60 mins. After an intravenous kisspeptin (9.6nmol/kg) bolus, LH rose from 5.05 to 29.99 IU/L, FSH from 6.68 to 13.91 IU/L. Off HRT, she began having regular cycles (estradiol 800 pmol/L). Discussion: CHH was diagnosed based on primary amenorrhea, HH and pathogenic GnRHR variant that would not, however, be expected to result in a productive phenotype in the absence of a second deleterious allele (oligogenicity occurs in 20% of CHH), so whole exome sequencing is awaited. Kisspeptin is a potent stimulator of hypothalamic GnRH neurons and can be used to interrogate hypothalamic function. Typically, gonadotrophin responses to kisspeptin are minimal in CHH. Thus, her kisspeptin response was not consistent with CHH at time of assessment, indicating reversal of CHH (seen in 20% of CHH, particularly with GnRHR variants). Notably, her kisspeptin response was higher than in healthy women, consistent with decreased hypothalamic function and potentially a ‘Female Obesity-Related Hypogonadism’. Our case highlights the value of interrogating hypothalamic function using kisspeptin, both for the diagnosis of CHH, and to identify alternate pathology, as well as to identify recovery of reproductive function in CHH reversal. Presentation: 6/1/2024

7521 Unmasking of PCOS after Microprolactinoma Treatment

Abstract Disclosure: F. Erenler: None. B. Aydogan Mathyk: None. Background: PCOS and prolactinomas are two of the leading causes of secondary amenorrhea. Hirsutism is a common finding for both diagnosis and can be the presenting symptom. We are presenting a case of secondary amenorrhea, initially diagnosed with microprolactinoma without signs of hyperandrogenism, which progressed to overt PCOS after prolactinoma treatment. Case: A 22-year-old female with history of Hashimoto’s hypothyroidism presented with secondary amenorrhea. Patient was on combined oral contraception pills (COC) for menstrual regulation and discontinued them with a desire of natural cycles. After the discontinuation of COC, her menstrual cycles did not return for four months and patient was subsequently found to have a microprolactinoma with prolactin (PRL) level 70.6 ng/mL - high (nl: 2.8-29.2 ng/mL), LH 6.1 mIU/mL (follicular phase: 1.9-12.5 mIU/mL), FSH 2.4 mIU/mL - low (follicular phase: 2.5-10.2 mIU/mL), androstenedione 132 ng/mL (follicular phase: 51-213 ng/mL), testosterone 36 ng/mL (nl: 2-45 ng/mL), AMH 33 ng/mL - high (nl: 1.02-14.63 ng/mL), DHEA-S 241 mcg/dL (nl: 44-286 mcg/dL), HCG neg. MR Sella showed a 0.5 cm hypoenchancing pituitary lesion, confirming the diagnosis of prolactinoma. Patient was started treatment with cabergoline 0.25 mg twice a week and PRL level trended down to 3.9 ng/mL. With normalization of PRL, patient started complaining of new onset hirsutism without return of her menses. Ferriman Gallway score was 8. Further workup showed elevated androgen markers: LH 25.7 mIU/mL - high (follicular phase: 1.9-12.5 mIU/mL), FSH 5.0 mIU/mL (follicular phase: 2.5-10.2 mIU/mL), PRL 4.7 ng/mL -low (nl: 4.8-23.2 ng/mL), androstenedione 341 ng/mL -high (41-262 ng/mL), E2 63.4 pg/mL (nl: 12.5-160 pg/mL), AMH 22.3 ng/mL – high (nl: 1.23-11.61 ng/mL), testosterone 94.7 ng/mL - high (nl: 10-55 ng/mL), DHEA-S 261 mcg/dL (nl:110-431.7 mcg/dL). ACTH stimulation test pursued to rule out NCAH and17-OH progesterone levels were within normal range after stimulation. Pelvis US obtained due to high suspicion for PCOS and was consistent with polycystic ovaries. The diagnosis of PCOS confirmed by Rotterdam criteria. Patient has phenotype A PCOS by the definition of NIH 2012 consensus. Conclusion: Hyperprolactinemia and pituitary adenomas can cause secondary amenorrhea. In our case, the treatment of hyperprolactinemia with cabergoline unmasked the underlying PCOS. The clinical and biochemical manifestation of PCOS became apparent following the removal of prolactin’s suppressive effect on GnRH. Presentation: 6/2/2024

Lower reporting of venous thromboembolisms events with natural estrogen-based combined oral contraceptives compared to ethinylestradiol-containing pills: A disproportionality analysis of the Eudravigilance database

ObjectivesPharmacovigilance data analysis can accelerate the identification of drug-related safety signals or reassure on the safety profile. This study evaluates the venous thromboembolism (VTE) risk of newer combined oral contraceptive (COC) formulations with natural estrogens, such as estradiol (E2) and estetrol (E4), using data from the EudraVigilance database. Study designWe conducted a disproportionality reporting rate analysis of VTE events associated with various COC formulations by extracting individual case reports from EudraVigilance database up to July 28, 2024. The study compared the proportionality reporting rate between natural estrogen-based COCs (E2 and E4) and conventional synthetic estrogen-based COCs (ethinylestradiol [EE]), with a comparison to EE-levonorgestrel. ResultsThe analysis revealed that COCs containing natural estrogens exhibited significantly lower proportionality reporting rates for thrombotic events compared to EE-based COCs. Specifically, E4-drospirenone (E4-DRSP) showed the lowest proportionality reporting rate (0.12), similar to progestin-only pills. EE-DRSP had the highest proportionality reporting rate (2.25), suggesting an increased thrombotic risk. ConclusionsThe study supports the safer thrombotic profile of natural estrogen-based COCs, particularly E2 and E4 formulations, over synthetic estrogen-based COCs containing EE. These findings support the hypothesis that E2- and E4-based pills are safer than EE-based pills, aligning with a shift toward safer contraceptive options in clinical practice. ImplicationsNatural estrogens such as E2 and E4 may emerge as safer alternatives to synthetic estrogens like EE, particularly when combined with progestins like DRSP. This multilevel evidence underscores the importance of evidence-based prescribing practices to enhance patient safety and minimize thrombotic risks associated with COC use.

Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

Endometrial Microcalcification in a 31-Year-Old Woman: A Case Report

Endometrial microcalcifications are an uncommon event, though they may be a cause of amenorrhoea and infertility. It is often detected incidentally as echogenic lesions on ultrasonography and in endometrial samples sent for histopathological examination. A 31-year-old Para 0+3 presented with amenorrhoea and a “curettage sample” obtained from an evacuation performed for a missed abortion at ten weeks gestation. She brought the tissue obtained during the endometrial curettage, which was performed at a private hospital for histopathological examination and follow-up at the Gynaecology Clinic. A provisional diagnosis of atrophic endometrium was made following a pelvic ultrasound scan, while histopathological examination revealed placenta tissue with microcalcifications. The patient was subsequently placed on combined oral contraceptives for three cycles, having ruled out possible contraindications. She had regular per vaginam bleeding for three consecutive cycles. She resumed spontaneous menses and eventually achieved pregnancy. Although endometrial microcalcification is rare, it is a potential cause of secondary amenorrhea and infertility in women of reproductive age group.

A comparative study of hormonal contraceptive use and vitamin D levels at Gondar Town 2023.

Vitamin D deficiency is an emerging public health problem globally, with devastating health consequences. Some studies suggest that exogenous sex hormones, found in hormonal contraceptives, may enhance vitamin D levels. However, the reasons for this association are not fully understood, as women using hormonal contraception may have different lifestyle habits affecting their vitamin D status. Therefore, this study seeks to explore the relationship between hormonal contraceptive use and vitamin D levels. A Facility based comparative cross-sectional study was conducted in Gondar town from February to April 2023, involving a total of 162 women using three types of hormonal contraceptives (Norplant, DMPA, and COC) and 162 age and BMI-matched non-users as controls in a 1:1 ratio. Participants were selected using systematic random sampling. A semi-structured questionnaire was used to collected data regarding the socio-demographic, economic, obstetric, lifestyle, and clinical information. 5 milliliters of blood samples were collected from each participant for Laboratory analysis of serum vitamin D, calcium, and alkaline phosphates using a Beckman Coulter chemistry analyzer. Independent t-tests, ANOVA with post hoc Bonferroni test was used to compare statistics between the two groups, and logistic regression models to identify factors associated with Vitamin D deficiency. The mean serum Vitamin D levels of Norplant, DMPA, and COC users were 24.08 (± 5.17), 24.83 (± 5.52), and 31.90 (± 6.94) respectively; whereas control group has mean Vitamin D level of 22.00 (± 7.97). On the current study the prevalence of Vitamin D deficiency (< 20 ng/ml) among hormonal contraceptive users was found to be 21.6% (35/162), whereas 48.14% (78/162) of non-user controls had vitamin D deficiency. The odds of having Vitamin D deficiency was higher among participants who attained higher education, who never eat fish and have never been used vitamin D Supplements. However, the use of combined oral contraceptives (COC) shown to reduce the odd of having vitamin D deficiency by 90%. Similarly, individuals with normal and hypercalcemia state shown to have lower odd of having Vitamin D deficiency. Users of combined oral contraceptives (COC) had significantly higher mean serum Vitamin D levels compared to users of Norplant and DMPA, as well as non-users. The prevalence of Vitamin D deficiency was lower among COC users compared to non-users, highlighting a potential protective effect of COC use against Vitamin D deficiency.

Oxidative Stress in Polycystic Ovary Syndrome: Impact of Combined Oral Contraceptives.

Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that is associated with heightened metabolic risks. While oxidative stress (OS) is known to play a role in PCOS, the precise nature of the relationship between PCOS and increased OS remains not entirely understood. Combined oral contraceptives (COCs) are the first-line treatment to regulate menstrual cycles and androgen levels, but their impact on oxidative stress requires further study. We conducted a transcriptomic analysis using RNAseq and assessed the levels of various oxidative stress (OS) markers in serum samples from women with PCOS and controls and whether they were using combined oral contraceptives (COCs), including enzymatic activities, FRAP, and 8-isoprostane (8-iso). A total of 359 genes were differentially expressed in women with PCOS compared to control women. Genes differentially expressed were enriched in functions related to inflammation and, interestingly, oxidative stress response. In controls, 8-iso levels were increased in women using COCs, whereas in women with PCOS, 8-iso levels were reduced in those using oral contraceptives (191.1 ± 97 vs. 26.4 ± 21 pg/mL, p: <0.0001). Correlation analyses showed a trend for a negative correlation between 8-iso and Ferriman score in women with PCOS consuming COCs (r = -0.86, p = 0.06) and a negative correlation between GSH and hyperandrogenism in women with PCOS (r = -0.89, p = 0.01). These results reveal the presence of lipid peroxidation in women with PCOS, which was modified by the use of COCs, providing new insights into the pathophysiology of PCOS in the Chilean population.

Factors associated with uterine fibroids in women of reproductive age: A cross-sectional study

Background. Uterine fibroids is a benign monoclonal tumor originating from the smooth muscle layer of the uterus. Non-modifiable risk factors for the development of uterine fibroids, such as age, ethnicity, age at menarche, etc, have been studied quite extensively, while the role of many controllable factors remains debatable.The aim of the study. To identify the main modifiable factors associated with uterine fibroids in women of reproductive age living in the Baikal region, including certain ethnic groups.Materials and methods. We carried out a multicenter cross-sectional study in 2016–2019 in institutions of Irkutsk and Bokhan (Irkutsk region) and Ulan-Ude (Republic of Buryatia). The subjects of the study were women to have annual workplace medical examination. The study included 1,347 participants of reproductive age (34.33 ± 6.37 years) who met the inclusion criteria. Among all women included in the study, there were 867 (64.37 %) Caucasians, 361 (26.80 %) Asians, and 119 (8.83%) women of mixed (Caucasian-Asian), ethnicity. The research methods included a questionnaire, general clinical and gynecological examination, and pelvic ultrasound examination.Results. According to our study, the main non-modifiable factors associated with the presence of uterine fibroids were: Asian ethnicity; age at menarche 12–13 years; age of the study participant 40–44 years; menopausal symptoms; adenomyosis. The “controllable” factors included: city residency; body mass index over 40 kg/m2; history of abortions and miscarriages; metabolic syndrome; using combined oral contraceptives; lack of sexual activity; smoking; presence of anumber of occupational hazards.Conclusion. Our study identified the main controllable factors associated with the presence of uterine fibroids in a multiethnic population of women of reproductive age.

A Complete Guide to Understand PMS (Pre-Menstrual Syndrome) in Women’s and its Effective Ayurvedic and Allopathic Treatment

Many women around the world are suffering from common physical discomfort just before their menstrual cycle. Symptoms may vary women to women which can be mild to severe such that it could affect their regular activities. Based on the diagnostic criteria, 2.5–3% of women of reproductive age have the severe form of PMS, while 40% of these women experience the moderate type. The symptoms seen were fluid retention, pain in pelvic region, mastalgia, psychological changes, behavioural changes, gastrointestinal problems, skin related problems and nervous system affecting problem. The targeting therapies to cure PMS includes allopathic as well as ayurvedic remedies. Allopathic includes mainly targeting brain SSRIs and some pharmacotherapies including administration of NSAIDs, anxiolytic agents, gonadotropin-releasing hormone (GnRH) agonists. etc. and recent studies shows combined oral contraceptives shows good effect to cure PMS prominently. And daily physical exercise can also overcome the PMS related problems wisely.

Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Firsocostat, a Liver-Targeted Inhibitor of Acetyl-CoA Carboxylase.

Firsocostat is an oral, liver-targeted inhibitor of acetyl-CoA carboxylase in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis. This work evaluated the potential drug-drug interactions (DDIs) of firsocostat as a victim and as a perpetrator, to inform concomitant medication use. In this phase I study, healthy participants (n=13-30 in each of four cohorts) received firsocostat alone or in combination with either victims or perpetrators of cytochrome P450 (CYP) enzymes and drug transporters to evaluate firsocostat as both a victim and perpetrator of DDIs, respectively. Overall, 80 participants completed the study. As a victim of DDI, firsocostat plasma exposure (area under the plasma concentration-time curve [AUC] from 0 to infinity [AUC∝]) was 19-fold, 22-fold, 63%, and 38% higher when administered with single-dose rifampin 600 mg (organic anion transporting polypeptide [OATP] 1B1/B3 inhibitor), single-dose cyclosporine A 600 mg (OATP/P-glycoprotein/CYP3A inhibitor), multiple-dose probenecid 500 mg twice daily (evaluated as a uridine diphosphate glucuronosyltransferase [UGT] inhibitor), and multiple-dose voriconazole 200 mg twice daily (CYP3A inhibitor), respectively, compared with the administration of firsocostat alone. As a perpetrator of DDI, multiple-dose administration of firsocostat did not affect the exposure of midazolam 2 mg (CYP3A substrate) or drospirenone/ethinylestradiol 3 mg/0.02 mg (combined oral contraceptive). Study treatments were well-tolerated and all adverse events were mild. Firsocostat can be administered with CYP3A and UGT inhibitors without dose adjustment. However, firsocostat should not be coadministered with strong OATP1B/3 inhibitors, such as rifampin and cyclosporine A. Firsocostat can be administered with CYP3A substrates or combined oral contraceptives without dose modification.

Effects of management of heavy menstrual bleeding of patients undergoing haploidentical hematopoietic stem cell transplantation.

To investigate the benefits of menstrual management in women undergoing hematopoietic stem cell transplantation (HSCT), in whom heavy menstrual bleeding (HMB) can be an underestimated bleeding complication. This was a retrospective cohort study. Patients who had undergone HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included over 10 years. The data of hematology and menstruation for all participants were collected. The management methods of the intervention group include gonadotropin-releasing hormone agonists (GnRHa), combined oral contraceptives (COC), or low-dose mifepristone. Patients who did not receive management were included in the control group. There were 112 patients included in the intervention group and 218 patients included in the control group. In all, 90.0%(297/330) of patients presented with HMB before HSCT. In the control group, 83.5%(182/218)of patients experienced menstruation in the laminar air-flow room (LAFR), whereas only 22.3%(25/112) did in the intervention group. After leaving the LAFR, the incidence of recurrent uterine bleeding was significantly reduced in the intervention group (17.9%(20/112/)versus 50.9%(111/218), p < 0.001). Patients who did not undergo menstrual management had a higher risk of bleeding than those who did (odds ratio 18.12, p < 0.001). Menstrual management significantly reduces the incidence of HMB in HSCT patients and acts as a protective factor to prevent menstrual bleeding in the LAFR.

“Killing two birds with one stone” – a qualitative study on women’s perspectives on the dual prevention pill in Johannesburg, South Africa

Background HIV incidence remains high in South Africa, with ~ 60% of all new HIV infections among adolescent girls and women (Country factsheets HIV and AIDS Estimates, 2022). Oral pre-exposure prophylaxis (PrEP), approved for HIV prevention in South Africa since 2015, is hampered by low uptake and adherence, particularly among adolescent girls and young women (AGYW). Combining oral PrEP with oral contraceptives could increase PrEP uptake, persistence and address unmet needs for contraception. We investigated the acceptability of a dual prevention pill (DPP), combining oral PrEP and a combined oral contraceptive (COC) for HIV and pregnancy prevention among women in Johannesburg, South Africa.MethodsBetween March-July 2021, we conducted 12 focus group discussions (FGDs) with adolescent girls and women (n = 74) aged 16–40 stratified by ages (16–17, 18–24, 25–40), half of whom were COC users. We explored adolescent girls and women’s opinions about the DPP concept, existing HIV and pregnancy prevention options, and input on perceived facilitators and barriers to DPP use. FGDs were conducted in English or isiZulu, using a standardized interview guide. FGDs were audio-recorded, transcribed to English and analyzed using ethnographic content analysis.ResultsThe majority viewed the DPP favorably as a multipurpose option preventing unplanned pregnancy and HIV. Most saw it as a convenient “two-in-one” solution, requiring one clinic visit for both PrEP and COCs. AGYW were viewed as the most likely to benefit from the DPP due to the likelihood of multiple partners and unplanned sex, possibly preventing school dropout from unplanned pregnancy or HIV acquisition. The DPP was perceived to be more reliable than condoms, especially when condom negotiation is limited. Benefits were also seen by participants in rape cases, protecting against pregnancy and HIV. DPP use barriers included side effect concerns, unsupportive partners and judgmental healthcare providers.Conclusions/significanceThe DPP was perceived as acceptable for HIV and pregnancy prevention to AGYW in Johannesburg and its dual indications helpful in supporting improved PrEP uptake and persistence. DPP implementation programs need to consider solutions to potential barriers, like education on DPP benefits, coupled with reliable side effect support and healthcare provider sensitization as part of routine sexual health services to encourage uptake and adherence.

The Pathophysiological Mechanism and Clinical Treatment of Polycystic Ovary Syndrome: A Molecular and Cellular Review of the Literature.

Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The pathogenesis of PCOS involves a complex interplay of genetic and environmental factors, including insulin resistance (IR) and resultant hyperinsulinemia. Insulin receptors, primarily in skeletal muscle, liver, and adipose tissue, activate downstream signaling pathways like PI3K-AKT and MAPK-ERK upon binding. These pathways regulate glucose uptake, storage, and lipid metabolism. Genome-wide association studies (GWASs) have identified several candidate genes related to steroidogenesis and insulin signaling. Environmental factors such as endocrine-disrupting chemicals and lifestyle choices also exacerbate PCOS traits. Other than lifestyle modification and surgical intervention, management strategies for PCOS can be achieved by using pharmacological treatments like antiandrogens, metformin, thiazolidinediones, aromatase inhibitor, and ovulation drugs to improve insulin sensitivity and ovulatory function, as well as combined oral contraceptives with or without cyproterone to resume menstrual regularity. Despite the complex pathophysiology and significant economic burden of PCOS, a comprehensive understanding of its molecular and cellular mechanisms is crucial for developing effective public health policies and treatment strategies. Nevertheless, many unknown aspects of PCOS, including detailed mechanisms of actions, along with the safety and effectiveness for the treatment, warrant further investigation.

Challenges to Contraceptive Counseling With Isotretinoin Treatment and Future Directions for Dermatologists

Accutane, also known as isotretinoin, is an oral systemic retinoid utilized in the treatment of severe, treatment-resistant acne. Isotretinoin is a pregnancy category X drug, meaning that studies have documented congenital defects in pregnant patients on isotretinoin. Known abnormalities include ear abnormalities, facial dysmorphia, cleft palate, CNS abnormalities, thymus gland abnormalities, and parathyroid hormone deficiencies. With teratogenicity well-documented with isotretinoin use, the iPLEDGE system was created to educate prescribers, pharmacists, and patients about the risks of isotretinoin use. Utilizing iPLEDGE, individuals of child bearing potential (ICBP) are required to document two negative pregnancy tests before the initiation of isotretinoin therapy with two documented forms of birth control. We conducted a literature review utilizing the terms: accutane, isotretinoin, contraception, and birth control. We found that amongst multiple articles, the most popular primary contraceptive methods in iPLEDGE were abstinence (47% of users) and combined oral contraceptives (31% of users). Individuals have attributed their lack of contraceptive use to fear of birth control health impacts and belief in the equivalent effectiveness of non-accepted methods (e.g. withdrawal and natural family planning. Despite the establishment of iPLEDGE to systematically reinforce counseling requirements, the incidence of isotretinoin-exposed pregnancies continues to persist with approximately 100-200 pregnancies annually. Given these findings, it is clear that counseling is tantamount to dispelling misconceptions regarding contraception and optimizing rates of patient compliance. Despite this importance, counseling remains a large issue for dermatologists. Only half of board-certified dermatology residents surveyed in 2023 felt comfortable providing counseling on adverse effects of combined oral contraceptives (COCs), and only 38.8% felt comfortable providing counseling directions for COCs. Solutions for this include quickly accessing a referral to primary care or OB/GYN and potentially new avenues that are more easily accessible such as the progestin-only oral contraceptive pill that was recently approved for over the counter use by the United States Food and Drug Administration.

Chronic venous disease of the lower extremities as a risk factor for PE when taking combined oral contraceptives: a clinical case

The use of combined oral contraceptives (COCs) is one of the risk factors for thrombotic complications, particularly pulmonary embolism (PE). Although clinical observations suggest that the risk of thrombotic complications with OCs is low and decreases after several months of use, medical counseling is necessary as with any other hormonal therapy. A clinical case of PE in a young patient taking COCs is presented. In the context of early diagnosis, thrombolysis was successful because thrombus retraction had not yet occurred. After completion of treatment of the underlying pathology, the patient was recommended to be followed up with a vascular surgeon for treatment of lower limb venous disease. Exclusion of lower extremity venous disease is critical before prescribing COCs, as it increases the risk of PE at any age.

Resting Energy Expenditure, Metabolic and Sex Hormones in Two Phases of the Menstrual and Hormonal Contraceptive Cycles.

Resting energy expenditure (REE) may fluctuate during the menstrual cycle (MC), due to the physiological effects of estradiol (E2) and progesterone (P4). This study examined changes in REE and metabolic hormones (leptin, ghrelin, thyroid hormones), and dietary intake in two hormonally distinct groups, naturally menstruating women (NoOC) and women using monophasic combined oral contraceptives (COC). Measurements included REE by indirect calorimetry, body composition by bioimpedance, and blood samples for hormone analysis in the early follicular and mid-luteal phases of the MC in NoOC-group (n = 38) or the active and inactive phases of the COC cycle (COC, n = 19). Participants recorded their food intake for 3 days after measurements. A secondary analysis was completed for the NoOC-group without REE outliers (difference between measurements >1.5 × interquartile range, n = 4). In the NoOC-group, luteal phase REE was 40 kcal higher than follicular phase REE [95% confidence interval (CI): -2 kcal/d-82 kcal/d, d = 0.20, p = 0.061]. Leptin (d = 0.35, p < 0.001), T3 (d = 0.26, p = 0.05) and fat intake (d = 0.48, p = 0.027) were lower, and T4 (d = 0.21, p = 0.041) was higher in the luteal phase. After excluding outliers, REE was 44 kcal higher in the luteal phase than in the follicular phase (95% CI: 12 kcal/d-76 kcal/d, d = 0.22, p = 0.007). In the COC-group, the mean difference in REE was -2 kcal (95% CI-82 kcal/d-79 kcal/d) between active and inactive phases, while T3 was higher in the inactive phase (d = 0.01, p = 0.037). REE increases only slightly from the follicular to the luteal phase but remains unchanged between COC phases. Increases in T3, leptin, and fat intake during the luteal phase might echo metabolic fluctuations that parallel female sex hormones during the MC.

The possibilities of predicting the individual risk of cervical cancer in women of reproductive age using mathematical modeling

Background. Cervical cancer (CC) refers to cancer of visual localization and in women of reproductive age remains one of the most common oncological diseases. The carcinogenesis of CC is caused by the persistence of highly oncogenic types of human papillomavirus (HPV), the level of carcinogenicity of which is the highest based on the criteria of the International Agency for Research on Cancer. However, cervical carcinogenesis does not occur in all cases of persistence of highly oncogenic types of HPV. This, in turn, determines the need for a thorough search, study and analysis of possible cofactors that can lead to neoplastic changes in the cervix.Aim. To develop a model for predicting the individual risk of CC in women of reproductive age, taking into account clinical, anamnestic, laboratory and histological data.Materials and methods. The material for the study was retrospective examination data from 251 patients of reproductive age who were treated at the Center for Gynecology and Reproductive Technologies of the National Medical Research Center “Medical and Rehabilitation Center”, Ministry of Health of Russia in the period 2015–2022. Results. Highly oncogenic HPV types were significantly more common in the group of patients with verified СС who took combined oral contraceptives (COC), compared with patients who did not take COC (p = 0.035). Multifactorial analysis allowed us to determine that long-term use of СОС for a total of more than 7 years is associated with a tendency to increase the risk of developing СС (hazard ratio 1.68; 95 % confidence interval 1.1–2.5; p = 0.010). According to the results of statistical calculation, the values of regression coefficients were obtained and the tendency to increase the risk of developing CC was predicted in the presence of such factors as: HPV type 16 persistence, body mass index, and the duration of COC intake in years.Conclusion. Thus, taking into account all possible risk factors for CC, the negative effect of cofactors, namely increased body mass index and prolonged intake of COC, on the course of HPV as the leading etiological factor of breast cancer, will allow us to identify groups at increased risk of developing CC, form an individual algorithm for monitoring and examination throughout the entire period of taking COC, as well as conduct individual cancer prevention by limiting the duration of taking COC.