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Scientific Reports Jan 2023To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing...
To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
Topics: Female; Humans; Chromatography, Liquid; Pilot Projects; Tandem Mass Spectrometry; Levonorgestrel; Medroxyprogesterone Acetate; Contraceptives, Oral, Combined
PubMed: 36604469
DOI: 10.1038/s41598-022-24215-4 -
Medical History Apr 2020The twentieth-century history of men and women's attempts to gain access to reproductive health services in the Republic of Ireland has been significantly shaped by...
The twentieth-century history of men and women's attempts to gain access to reproductive health services in the Republic of Ireland has been significantly shaped by Ireland's social and religious context. Although contraception was illegal in Ireland from 1935 to 1979, declining family sizes in this period suggest that many Irish men and women were practising fertility control measures. From the mid-1960s, the contraceptive pill was marketed in Ireland as a 'cycle regulator'. In order to obtain a prescription for the pill, Irish women would therefore complain to their doctors that they had heavy periods or irregular cycles. However, doing so could mean going against one's faith, and also depended on finding a sympathetic doctor. The contraceptive pill was heavily prescribed in Ireland during the 1960s and 1970s as it was the only contraceptive available legally, albeit prescribed through 'coded language'. The pill was critiqued by men and women on both sides of the debate over the legalisation of contraception. Anti-contraception activists argued that the contraceptive pill was an abortifacient, while both anti-contraception activists and feminist campaigners alike drew attention to its perceived health risks. As well as outlining these discussions, the paper also illustrates the importance of medical authority in the era prior to legalisation, and the significance of doctors' voices in relation to debates around the contraceptive pill. However, in spite of medical authority, it is clear that Irish women exercised significant agency in gaining access to the pill.
Topics: Catholicism; Contraception; Contraceptives, Oral; Family Planning Services; Female; Feminism; History, 20th Century; Humans; Ireland; Male; Physician's Role; Physician-Patient Relations; Religion and Medicine; Women's Rights
PubMed: 32284634
DOI: 10.1017/mdh.2020.3 -
Gynecological Endocrinology : the... Jun 2023To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, -acetylcysteine, vitamin B, and -adenosyl-L-methionine) for the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, -acetylcysteine, vitamin B, and -adenosyl-L-methionine) for the modulation of metabolic, endocrine, and clinical parameters in comparison with oral contraception in non-diabetic women newly diagnosed with polycystic ovary syndrome (PCOS).
METHODS
This was a prospective, partially randomized, multicenter study in which non-diabetic women with PCOS were recruited under routine clinical practice conditions and distributed in three groups to receive the following regimen for 6 months: 1) antioxidant combination (MN group); 2) oral contraception (OC group); or 3) oral contraception and the antioxidant combination (MN + OC group). General recommendation of healthy diet and regular exercise was given to all patients. Metabolic, endocrine, clinical, and quality of life parameters were recorded at baseline and after 6 months of therapy.
RESULTS
A total of 96 women with PCOS were included in the study. After 6 months of treatment, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) level was reduced only in the MN group, with a significant mean reduction of -0.92 points. Androstenedione was significantly reduced in all groups. Clinical parameters that significantly improved in all groups were hirsutism, acne, irregular menstruation, and quality of life, with no statistical differences between the groups.
CONCLUSIONS
This study showed that the antioxidant combination might be a suitable therapy for patients with PCOS when oral contraceptive is not indicated, because in all groups clinical parameters, irregular menstruation as well as androstenedione and quality of life were significantly improved with no statistical difference between groups.
Topics: Female; Humans; Androstenedione; Antioxidants; Insulin Resistance; Menstruation Disturbances; Polycystic Ovary Syndrome; Prospective Studies; Quality of Life; Contraceptives, Oral; Dietary Supplements
PubMed: 37356455
DOI: 10.1080/09513590.2023.2227277 -
Journal of the National Cancer Institute Oct 2017With recent ovarian cancer screening studies showing no clinically significant mortality benefit, preventing this disease, identifying high-risk populations, and... (Review)
Review
With recent ovarian cancer screening studies showing no clinically significant mortality benefit, preventing this disease, identifying high-risk populations, and extending survival remain priorities. However, several challenges are impeding progress in ovarian cancer research. With most studies capturing exposure information from 10 or more years ago, evaluation of how changing patterns of exposures, such as new oral contraceptive formulations and increased intrauterine device use, might influence ovarian cancer risk and survival is difficult. Risk factors for ovarian cancer should be evaluated in the context of tumor histotypes, which have unique molecular features and cells of origin; this is a task that requires large collaborative studies to achieve meaningful sample sizes. Importantly, identification of novel modifiable risk factors, in addition to those currently known to reduce risk (eg, childbearing, tubal ligation, oral contraceptive use), is needed; this is not feasibly implemented at a population level. In this Commentary, we describe important gaps in knowledge and propose new approaches to advance epidemiologic research to improve ovarian cancer prevention and survival, including updated classification of tumors, collection of data on changing and novel exposures, longer follow-up on existing studies, evaluation of diverse populations, development of better risk prediction models, and collaborating prospectively with consortia to develop protocols for new studies that will allow seamless integration for future pooled analyses.
Topics: Bias; Contraceptives, Oral; Epidemiologic Research Design; Epidemiologic Studies; Female; Health Services Needs and Demand; Humans; Ovarian Neoplasms; Risk Factors
PubMed: 29117355
DOI: 10.1093/jnci/djx144 -
British Journal of Clinical Pharmacology Dec 2015Hormonal contraceptives are highly prevalent. Currently, little is known about Irish hormonal contraceptive trends to date since the 1995 British media contraceptive... (Review)
Review
Hormonal contraceptives are highly prevalent. Currently, little is known about Irish hormonal contraceptive trends to date since the 1995 British media contraceptive controversy. The aim of this study was to examine recent trends in contraceptive use in Ireland and to determine the frequency of co-prescriptions with important interacting medications. Approximately 40% of the Irish population are prescribed 70% of total medicines under the Irish GMS scheme. Medicines were identified using the WHO Anatomical Therapeutic Chemical (ATC) classification system. Regression analysis was used to examine trends over time. Of all contraceptives dispensed in 2013, oral contraceptives were used the most (74%) and long acting reversible contraceptives (LARCs) the least (7.5%). Fourth generation combined oral contraceptives (COCs) predominated, although a slight significant decline was shown (P < 0.0001). Second and third generation COCs were significantly increasing and decreasing, respectively (P < 0.0001). Progestin-only pills were significantly increasing (P < 0.0001 across age groups). Low rates of contraceptive co-prescribing with important interacting drugs are shown. However, 93.6% of those on enzyme-inducing anti-epileptic medications were co-prescribed ineffective contraception containing <50 μg oestrogen.Irish prescribing trends of second and third generation COCs have remained consistent since 1995. The slow decline in fourth generation COC uptake follows new evidence of an increased risk of venous thromboembolism (VTE) reported in 2011. The low, but increasing, uptake of LARCs is consistent with other countries. Co-prescribing practices involving hormonal contraceptives requires continued vigilance. This study emphasizes the need to optimize co-prescribing practices involving hormonal contraceptives and anti-epileptic medications and highlights the need to address the barriers to the currently low uptake of LARC methods in Ireland.
Topics: Adolescent; Adult; Anticonvulsants; Contraceptives, Oral, Hormonal; Drug Interactions; Drug Prescriptions; Female; Humans; Ireland
PubMed: 26503402
DOI: 10.1111/bcp.12755 -
Cytokine Oct 2022Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release...
The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia.
PURPOSE
Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia.
METHODS
Twenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 μg·mL LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA.
RESULTS
L:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001).
CONCLUSIONS
Men present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases.
Topics: Contraceptives, Oral; Female; Humans; Hyperthermia, Induced; Lipopolysaccharides; Male; Menstrual Cycle; Monocytes; Permeability; Tumor Necrosis Factor-alpha
PubMed: 35944412
DOI: 10.1016/j.cyto.2022.155991 -
Contraception Dec 2016Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated... (Review)
Review
BACKGROUND
Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated with an increased risk of ischemic stroke. Use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age.
OBJECTIVE
To identify evidence regarding the risk of arterial thromboembolism (stroke or myocardial infarction) among women with migraine who use hormonal contraceptives.
METHODS
We searched the PubMed database for all articles published from database inception through January 2016. We included studies that examined women with migraine overall or separated by subtype (with or without aura). Hormonal contraceptives of interest included combined hormonal methods (COCs, patch and ring) and progestin-only methods (progestin-only pills, injectables, implants and progestin intrauterine devices).
RESULTS
Seven articles met inclusion criteria. All were case-control studies of fair to poor quality reporting on use of COCs or oral contraceptives (OCs) not further described and all reported stroke outcomes. Four studies demonstrated that, among women with migraine (not separated by subtype), COC use was associated with approximately two to four times the risk of stroke compared with nonuse. The only study to examine specific migraine subtypes found an elevated risk of stroke among women with migraine with aura, and this risk was similar regardless of OC use, although these odds ratios were not reported. Two studies did not report risks among women with migraine and COC use combined, but both found increased risks of stroke with migraine and COC use independently. No evidence was found on other hormonal contraceptives or on risk of myocardial infarction.
CONCLUSION
Limited evidence suggests a two- to fourfold increased risk of stroke among women with migraine who use COCs compared with nonuse. Additional study is needed on the risks of hormonal contraceptives, including combined and progestin-only methods, among women with different migraine subtypes.
Topics: Contraceptive Devices, Female; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Female; Humans; Migraine Disorders; Myocardial Infarction; Progestins; Risk Assessment; Stroke
PubMed: 27153744
DOI: 10.1016/j.contraception.2016.04.016 -
Fertility and Sterility Oct 2015Although surgical excision of endometriosis both improves pain and enhances fertility, recurrence can further exacerbate pain and reduce fertility, which in turn impacts... (Review)
Review
Although surgical excision of endometriosis both improves pain and enhances fertility, recurrence can further exacerbate pain and reduce fertility, which in turn impacts the quality of life and increases personal as well as social costs. Therefore, it is crucial to prevent the recurrence of symptoms and lesions after conservative surgery. This article reviews evidence regarding the prevention of postoperative recurrence of endometriosis reported since the 1990s. Over the past 5 years, many new studies have been conducted and have demonstrated that long-term postoperative medication markedly reduces the recurrence. Most of these studies used oral contraceptives (OC), with either the cyclic or continuous regimen, while some used oral or intrauterine progestin. Continuous OC is more efficacious than cyclic OC, especially for dysmenorrhea. The levonorgestrel-releasing intrauterine system is also shown to prevent recurrence of dysmenorrhea and possibly endometriosis lesions. Dienogest, a new progestin, is shown to reduce the recurrence of endometrioma. Similar to the case of ovarian endometriosis, long-term postoperative medication after conservative surgery for deep infiltrating or extragenital endometriosis seems important, although data are limited. Regardless of the lesion and the medication type, patients who discontinued medication experienced a higher incidence of recurrence, indicating that the protective effect of these medications seems to vanish rapidly after the discontinuation. On the basis of these facts, together with the pathogenesis of recurrence (retrograde menstruation and ovulation), regular and prolonged medication until the patient wishes to conceive is highly recommended to prevent the postoperative recurrence of endometriosis.
Topics: Analgesics; Contraceptives, Oral; Endometriosis; Female; Fertility Preservation; Humans; Organ Sparing Treatments; Pain Management; Secondary Prevention
PubMed: 26354093
DOI: 10.1016/j.fertnstert.2015.08.026 -
Journal of Applied Physiology... Apr 2023The purpose of this study was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilation between women in either menstrual or placebo pill...
The purpose of this study was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilation between women in either menstrual or placebo pill phases of their respective hormonal exposure [either naturally cycling (NC) or using oral contraceptive pills (OCPs)] and men. A planned subgroup analysis was then completed to assess endothelial function and NO-dependent vasodilation between NC women, women using OCP, and men. Endothelium-dependent and NO-dependent vasodilation were assessed in the cutaneous microvasculature using laser-Doppler flowmetry, a rapid local heating protocol (39°C, 0.1 °C/s), and pharmacological perfusion through intradermal microdialysis fibers. Data are represented as means ± standard deviation. Men displayed greater endothelium-dependent vasodilation (plateau, men: 71 ± 16 vs. women: 52 ± 20%CVC, < 0.01), but lower NO-dependent vasodilation (men: 52 ± 11 vs. women: 63 ± 17%NO, = 0.05) compared with all women. Subgroup analysis revealed NC women had lower endothelium-dependent vasodilation (plateau, NC women: 48 ± 21%CVC, = 0.01) but similar NO-dependent vasodilation (NC women: 52 ± 14%NO, > 0.99), compared with men. Endothelium-dependent vasodilation did not differ between women using OCP and men ( = 0.12) or NC women ( = 0.64), but NO-dependent vasodilation was significantly greater in women using OCP (74 ± 11%NO) than both NC women and men ( < 0.01 for both). This study highlights the importance of directly quantifying NO-dependent vasodilation in cutaneous microvascular studies. This study also provides important implications for experimental design and data interpretation. This study supports differences in microvascular endothelial function and nitric oxide (NO)-dependent vasodilation between women in low hormone phases of two hormonal exposures and men. However, when separated into subgroups of hormonal exposure, women during placebo pills of oral contraceptive pill (OCP) use have greater NO-dependent vasodilation than naturally cycling women in their menstrual phase and men. These data improve knowledge of sex differences and the effect of OCP use on microvascular endothelial function.
Topics: Female; Humans; Male; Contraceptives, Oral; Endothelium; Nitric Oxide; Skin; Skin Physiological Phenomena; Vasodilation
PubMed: 36861674
DOI: 10.1152/japplphysiol.00586.2022 -
JNCI Cancer Spectrum Jul 2022Hormone-replacement therapy (HRT) is associated with lower colorectal cancer (CRC) risk among postmenopausal women. However, little is known about the effects of...
BACKGROUND
Hormone-replacement therapy (HRT) is associated with lower colorectal cancer (CRC) risk among postmenopausal women. However, little is known about the effects of lifetime exposure of women to varying levels of estrogen and progesterone through reproductive factors such as parity, use of oral contraceptives (OC), breastfeeding, and menstruation on CRC risk.
METHODS
We assessed associations between reproductive factors and CRC risk among 2650 female CRC patients aged 30+ years and 2175 matched controls in a population-based study in Germany, adjusting for potential confounders by multiple logistic regression.
RESULTS
Inverse associations with CRC risk were found for numbers of pregnancies (odds ratio [OR] per pregnancy = 0.91, 95% confidence interval [CI] = 0.86 to 0.97), breastfeeding for 12 months and longer (OR = 0.74, 95% CI = 0.61 to 0.90), and use of either OC or HRT (OR = 0.75, 95% CI = 0.64 to 0.87) or both (OR = 0.58, 95% CI = 0.48 to 0.70). Similar results were found for postmenopausal women only and when adjusting for number of pregnancies and for all reproductive factors analyzed together. Breastfeeding duration of 12 months and longer was associated with lower risk of cancer only in the proximal colon (OR = 0.58, 95% CI = 0.45 to 0.74).
CONCLUSIONS
Several reproductive factors were associated with lower CRC risk in women, including number of pregnancies, breastfeeding duration, and use of OC and HRT. This suggests that women's exposure to female reproductive hormones plays a key role in the difference in CRC risk between women and men and in site-specific CRC risk.
Topics: Case-Control Studies; Colorectal Neoplasms; Contraceptives, Oral; Female; Humans; Male; Odds Ratio; Pregnancy; Reproductive History; Risk Factors
PubMed: 35642982
DOI: 10.1093/jncics/pkac042