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Expert Review of Clinical Pharmacology Jul 2020The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg... (Review)
Review
INTRODUCTION
The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties.
AREAS COVERED
This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns.
EXPERT OPINION
The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea).
Topics: Androstenes; Animals; Contraceptives, Oral, Hormonal; Drug Administration Schedule; Female; Humans; Mineralocorticoid Receptor Antagonists
PubMed: 32538188
DOI: 10.1080/17512433.2020.1783247 -
Sports Medicine (Auckland, N.Z.) Oct 2020Oral contraceptive pills (OCPs) are double agents, which downregulate endogenous concentrations of oestradiol and progesterone whilst simultaneously providing daily... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral contraceptive pills (OCPs) are double agents, which downregulate endogenous concentrations of oestradiol and progesterone whilst simultaneously providing daily supplementation of exogenous oestrogen and progestin during the OCP-taking days. This altered hormonal milieu differs significantly from that of eumenorrheic women and might impact exercise performance, due to changes in ovarian hormone-mediated physiological processes.
OBJECTIVE
To explore the effects of OCPs on exercise performance in women and to provide evidence-based performance recommendations to users.
METHODS
This review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A between-group analysis was performed, wherein performance of OCP users was compared with naturally menstruating women, and a within-group analysis was conducted, wherein performance during OCP consumption was compared with OCP withdrawal. For the between-group analysis, women were phase matched in two ways: (1) OCP withdrawal versus the early follicular phase of the menstrual cycle and (2) OCP consumption versus all phases of the menstrual cycle except for the early follicular phase. Study quality was assessed using a modified Downs and Black Checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation working group. All meta-analyses were conducted within a Bayesian framework to facilitate probabilistic interpretations.
RESULTS
42 studies and 590 participants were included. Most studies (83%) were graded as moderate, low or very low quality, with 17% achieving high quality. For the between-group meta-analysis comparing OCP users with naturally menstruating women, posterior estimates of the pooled effect were used to calculate the probability of at least a small effect (d ≥ 0.2). Across the two between-group comparison methods, the probability of a small effect on performance favouring habitual OCP users was effectually zero (p < 0.001). In contrast, the probability of a small effect on performance favouring naturally menstruating women was moderate under comparison method (1) (d ≥ 0.2; p = 0.40) and small under comparison method (2) (d ≥ 0.2; p = 0.19). Relatively large between-study variance was identified for both between-group comparisons ([Formula: see text] = 0.16 [95% credible interval (CrI) 0.01-0.44] and [Formula: see text] = 0.22 [95% CrI 0.06-0.45]). For the within-group analysis comparing OCP consumption with withdrawal, posterior estimates of the pooled effect size identified almost zero probability of a small effect on performance in either direction (d ≥ 0.2; p ≤ 0.001).
CONCLUSIONS
OCP use might result in slightly inferior exercise performance on average when compared to naturally menstruating women, although any group-level effect is most likely to be trivial. Practically, as effects tended to be trivial and variable across studies, the current evidence does not warrant general guidance on OCP use compared with non-use. Therefore, when exercise performance is a priority, an individualised approach might be more appropriate. The analysis also indicated that exercise performance was consistent across the OCP cycle.
Topics: Athletic Performance; Contraceptives, Oral; Exercise; Female; Humans
PubMed: 32666247
DOI: 10.1007/s40279-020-01317-5 -
BMJ (Clinical Research Ed.) Jan 2019
Comparative Study
Topics: Contraceptives, Oral; Cross-Sectional Studies; Female; Humans; Prospective Studies; Sexuality; United Kingdom; Women's Health
PubMed: 30683650
DOI: 10.1136/bmj.l335 -
European Journal of Obstetrics,... Apr 2020Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear.
OBJECTIVE
To evaluate risk of cervical cancer in OC users and non-users through a comprehensive systematic review.
SEARCH STRATEGY
Literature search conducted in databases from January 1990 till August 2019 using various search terms.
SELECTION CRITERIA
Primary research studies that evaluated and assessed the association of OC use with cervical cancer with study design of case control or cohort types published in English language.
DATA COLLECTION AND ANALYSIS
PRISMA guided review was done by two independent researchers. Effect size estimated by pooled Odds ratio with 95 % Confidence Interval (CI) in random effect models on OC pill use for the risk of cervical cancer.
RESULTS
Review included 19 studies. Overall risk of invasive cancer on OC use was found to be significant with unknown status of HPV OR (95 % CI) as 1.51 (1.35, 1.68) and for unknown HPV as 1.66 (1.24, 2.21). Adenocarcinoma, squamous cell carcinoma and carcinoma in situ had significant association with OR (95 % CI) of 1.77 (1.4, 2.24), 1.29 (1.18, 1.42) and 1.7 (1.18, 2.44) respectively.
CONCLUSION
OC pills use had a definite associated risk for developing cervical cancer specially for Adenocarcinoma and longer duration of OC pills use.
Topics: Adenocarcinoma; Contraceptives, Oral; Female; Humans; Risk; Uterine Cervical Neoplasms
PubMed: 32114321
DOI: 10.1016/j.ejogrb.2020.02.014 -
JAMA Psychiatry Jan 2020Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with...
IMPORTANCE
Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with concurrent depressive symptoms remains unclear.
OBJECTIVES
To investigate the association between oral contraceptive use and depressive symptoms and to examine whether this association is affected by age and which specific symptoms are associated with oral contraceptive use.
DESIGN, SETTING, AND PARTICIPANTS
Data from the third to sixth wave of the prospective cohort study Tracking Adolescents' Individual Lives Survey (TRAILS), conducted from September 1, 2005, to December 31, 2016, among females aged 16 to 25 years who had filled out at least 1 and up to 4 assessments of oral contraceptive use, were used. Data analysis was performed from March 1, 2017, to May 31, 2019.
EXPOSURE
Oral contraceptive use at 16, 19, 22, and 25 years of age.
MAIN OUTCOMES AND MEASURES
Depressive symptoms were assessed by the DSM-IV-oriented affective problems scale of the Youth (aged 16 years) and Adult Self-Report (aged 19, 22, and 25 years).
RESULTS
Data from a total of 1010 girls (743-903 girls, depending on the wave) were analyzed (mean [SD] age at the first assessment of oral contraceptive use, 16.3 [0.7]; (mean [SD] age at the final assessment of oral contraceptive use, 25.6 [0.6] years). Oral contraceptive users particularly differed from nonusers at age 16 years, with nonusers having a higher mean (SD) socioeconomic status (0.17 [0.78] vs -0.15 [0.71]) and more often being virgins (424 of 533 [79.5%] vs 74 of 303 [24.4%]). Although all users combined (mean [SD] ages, 16.3 [0.7] to 25.6 [0.6] years) did not show higher depressive symptom scores compared with nonusers, adolescent users (mean [SD] age, 16.5 [0.7] years) reported higher depressive symptom scores compared with their nonusing counterparts (mean [SD] age, 16.1 [0.6] years) (mean [SD] score, 0.40 [0.30] vs 0.33 [0.30]), which persisted after adjustment for age, socioeconomic status and ethnicity (β coefficient for interaction with age, -0.021; 95% CI, -0.038 to -0.005; P = .0096). Adolescent contraceptive users particularly reported more crying (odds ratio, 1.89; 95% CI, 1.38-2.58; P < .001), hypersomnia (odds ratio, 1.68; 95% CI, 1.14-2.48; P = .006), and more eating problems (odds ratio, 1.54; 95% CI, 1.13-2.10; P = .009) than nonusers.
CONCLUSIONS AND RELEVANCE
Although oral contraceptive use showed no association with depressive symptoms when all age groups were combined, 16-year-old girls reported higher depressive symptom scores when using oral contraceptives. Monitoring depressive symptoms in adolescents who are using oral contraceptives is important, as the use of oral contraceptives may affect their quality of life and put them at risk for nonadherence.
Topics: Adolescent; Adult; Age Factors; Case-Control Studies; Contraceptives, Oral; Depression; Female; Humans; Psychiatric Status Rating Scales; Socioeconomic Factors; Young Adult
PubMed: 31577333
DOI: 10.1001/jamapsychiatry.2019.2838 -
Acta Obstetricia Et Gynecologica... Dec 2019Approximately 100 million women currently use combined oral contraceptives. Combined oral contraceptives use is associated with increased risk of venous thromboembolic...
INTRODUCTION
Approximately 100 million women currently use combined oral contraceptives. Combined oral contraceptives use is associated with increased risk of venous thromboembolic events and cardiovascular disease. Progestin-only pills do not increase the risk of venous thromboembolic events, stroke and myocardial infarction but are associated with a poor cycle control. A novel estrogen-free pill containing only drospirenone (DRSP) was developed to improve bleeding pattern, tolerability and acceptance without increasing venous thromboembolic events risks in contraception.
MATERIAL AND METHODS
Two prospective, multicenter Phase III studies in healthy women aged 18-45 years were performed to demonstrate the efficacy and safety of a drospirenone-only pill in a regimen of 24 days of 4 mg of drospirenone tablets followed by 4 days of placebo. A total of 1571 women (14 329 exposure cycles) were analyzed: 713 patients in the 13-cycle study 1 with 7638 exposure cycles and 858 patients in the 9-cycle study 2 with 6691 exposure cycles. The primary endpoint was the overall Pearl index, calculated for each study separately, and for both pooled. As main secondary efficacy endpoint, the "method failure Pearl index" including all pregnancies during "perfect medication cycles" was evaluated. EudraCT registration numbers: 2010-021787-15 & 2011-002396-42.
RESULTS
Calculations on pooled studies 1 and 2 with 1571 patients gave an overall Pearl index (based on 14 329 cycles) of 0.7258 (95% CI 0.3133 to 1.4301). No single case of deep vein thrombosis or pulmonary embolism and only one case of hyperkalemia were reported. Additional information such as laboratory parameters, body mass index, bodyweight, heart rate and blood pressure showed no statistically significant changes due to the treatment.
CONCLUSIONS
This is the first report of a new drospirenone-only oral contraceptive providing clinical efficacy similar to combined oral contraceptives, with a good safety profile, and favorable cycle control.
Topics: Adult; Androstenes; Contraceptives, Oral; Female; Humans; Hyperkalemia; Metrorrhagia; Pregnancy; Pregnancy Rate; Prospective Studies; Pulmonary Embolism; Treatment Failure; Venous Thrombosis; Young Adult
PubMed: 31321765
DOI: 10.1111/aogs.13688 -
Sports Medicine (Auckland, N.Z.) Jan 2020Resistance training is well known to increase strength and lean body mass, and plays a key role in many female athletic and recreational training programs. Most females...
BACKGROUND
Resistance training is well known to increase strength and lean body mass, and plays a key role in many female athletic and recreational training programs. Most females train throughout their reproductive years when they are exposed to continuously changing female steroid hormone profiles due to the menstrual cycle or contraceptive use. Therefore, it is important to focus on how female hormones may affect resistance training responses.
OBJECTIVE
The aim of this systematic review is to identify and critically appraise current studies on the effect of the menstrual cycle and oral contraceptives on responses to resistance training.
METHODS
The electronic databases Embase, PubMed, SPORTDiscus and Web of Science were searched using a comprehensive list of relevant terms. Studies that investigated the effect of the menstrual cycle phase or oral contraceptive cycle on resistance training responses were included. Studies were also included if they compared resistance training responses between the natural menstrual cycle and oral contraceptive use, or if resistance training was adapted to the menstrual cycle phase or oral contraceptive phase. Studies were critically appraised with the McMasters Universities Critical Review Form for Quantitative Studies and relevant data were extracted.
RESULTS
Of 2007 articles found, 17 studies met the criteria and were included in this systematic review. The 17 included studies had a total of 418 participants with an age range of 18-38 years. One of the 17 studies found no significant differences in acute responses to a resistance training session over the natural menstrual cycle, while four studies did find changes. When assessing the differences in acute responses between the oral contraceptive and menstrual cycle groups, two studies reported oral contraceptives to have a positive influence, whilst four studies reported that oral contraceptive users had a delayed recovery, higher levels of markers of muscle damage, or both. For the responses to a resistance training program, three studies reported follicular phase-based training to be superior to luteal phase-based training or regular training, while one study reported no differences. In addition, one study reported no differences in strength development between oral contraceptive and menstrual cycle groups. One further study reported a greater increase in type I muscle fibre area and a trend toward a greater increase in muscle mass within low-androgenic oral contraceptive users compared with participants not taking hormonal contraceptives. Finally, one study investigated androgenicity of oral contraceptives and showed greater strength developments with high androgenic compared with anti-androgenic oral contraceptive use.
CONCLUSIONS
The reviewed articles reported conflicting findings, and were often limited by small participant numbers and methodological issues, but do appear to suggest female hormones may affect resistance training responses. The findings of this review highlight the need for further experimental studies on the effects of the menstrual cycle and oral contraceptives on acute and chronic responses to resistance training.
Topics: Body Composition; Contraceptives, Oral; Female; Humans; Menstrual Cycle; Muscle Strength; Resistance Training
PubMed: 31677121
DOI: 10.1007/s40279-019-01219-1 -
Annals of Internal Medicine Feb 2015This issue provides a clinical overview of Perimenopause focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In... (Review)
Review
This issue provides a clinical overview of Perimenopause focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.
Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Diagnosis, Differential; Female; Hot Flashes; Humans; Mood Disorders; Perimenopause; Prevalence; Risk Factors; Sexual Dysfunction, Physiological; Sleep Wake Disorders; Uterine Hemorrhage
PubMed: 25643316
DOI: 10.7326/AITC201502030 -
Journal of Science and Medicine in Sport Jul 2023Menstrual health represents a state of complete physical, mental, and social well-being in relation to a woman's menstrual cycle. From a health literacy perspective,... (Review)
Review
Menstrual health represents a state of complete physical, mental, and social well-being in relation to a woman's menstrual cycle. From a health literacy perspective, knowledge acquisition and expertise are dependent upon the degree to which an individual can find, access, understand, critically analyse, and apply health information. Therefore, menstrual health literacy can be used to describe the state of knowledge acquisition and application specific to menstrual health-related issues. Menstrual health literacy is low among female athletes, their coaches, and practitioners, and few evidence-informed education or implementation strategies exist to improve menstrual health literacy in sport. Moreover, athletes seldom discuss their menstrual cycles or hormonal contraceptive use with their coaches, despite experiencing menstrual symptoms and/or disturbances and perceiving their menstrual cycles/hormonal contraceptive use to affect performance. Barriers to communication about menstrual cycle- and hormonal contraceptive-related topics include a perceived lack of knowledge among athletes, coaches, and practitioners, concerns about how conversations on these issues will affect interpersonal relationships, and a lack of formal and informal discussion forums. Whilst evidence relating to the effects of the menstrual cycle phase and hormonal contraceptive use on training and performance is currently limited, with existing studies often lacking methodological rigour, impactful steps can still be made to support female athletes. This cornerstone review highlights the current state of menstrual health literacy among athletes, coaches, and practitioners, and provides recommendations for improving menstrual health literacy in sport.
Topics: Humans; Female; Health Literacy; Sports; Athletes; Contraceptives, Oral; Menstrual Cycle
PubMed: 37407335
DOI: 10.1016/j.jsams.2023.06.007 -
Osteoporosis International : a Journal... Dec 2019Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity... (Review)
Review
Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.
Topics: Age Factors; Androstenes; Bone Density; Bone Development; Bone Remodeling; Bone Resorption; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Estradiol; Estrogens; Female; Humans; Progestins
PubMed: 31446440
DOI: 10.1007/s00198-019-05103-6