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Background
In recent years, several new oral contraceptives have become available. In some ways, they represent an evolution in terms of individualization and compliance on the part of women. The new formulations make it increasingly possible to prescribe a specific hormonal contraceptive on an individual basis.
Methods
A systematic literature sea...
Context in source publication
Context 1
... COCs do not work, it is possible to associate anti-androgens with contraceptives to reinforce their effect (Fig. 2). Anti-androgens are compounds that interfere with androgens, compete with them for receptors or reduce peripheral 5α-reductase activity. They include cyproterone acetate (CPA), a powerful progestin that may be administered with EE as a contraceptive pill: EE 35 µg + CPA 2 mg 21/7 regime or 12.5, 25 or 50 mg CPA + 20-30 µg EE with a ...
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Background
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Background: Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disease among women of childbearing age, affecting women throughout life on their reproductive, metabolic and cardiovascular health, as well as psychological health. Aerobic exercise is an important solution used to manage PCOS, due to its multiple benefits. Yi...
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Citations
... Evidence suggests that modern contraception contributes to improved women's health by reducing unintended and high-risk pregnancies, both of which can be stressful for any person [4]. Additionally, it is known that women who practice appropriate spacing of pregnancies and births (> 18 months) can focus more on their own physical and mental health as well as the health of other children and other family members [5]. Moreover, the impact of contraception on women's socioeconomic status is well documented. ...
Background
Contraceptive use is the principal method by which women avoid unintended pregnancy. An unintended pregnancy can induce long-term distress related to the medical, emotional, and social consequences of carrying that pregnancy to term.
Objectives
This review investigates the effects of modern contraception techniques such as birth control pills, long-acting reversible contraceptives (e.g., intrauterine devices, implants), and condoms on mental health status.
Methods
We searched multiple databases from inception until February 2022, with no geographical boundaries. RCTs underwent a quality assessment using the GRADE approach while the quality of observational studies was assessed using the Downs and Black scoring system. Data were analyzed through meta-analysis and relative risk and mean difference were calculated and forest plots were created for each outcome when two or more data points were eligible for analysis.
Main results
The total number of included studies was 43. In women without previous mental disorders, both RCTs (3 studies, SMD 0.18, 95% CI [0.02, 0.34], high quality of evidence) and cohort studies (RR 1.04 95% CI [1.03, 1.04]) detected a slight increase in the risk of depression development. In women with previous mental disorders, both RCTs (9 studies, SMD − 0.15, 95% CI [-0.30, -0.00], high quality of evidence) and cohort studies (SMD − 0.26, 95% CI [-0.37, -0.15]) detected slight protective effects of depression development. It was also noticed that HC demonstrated protective effects for anxiety in both groups (SMD − 0.20, 95% CI [-0.40, -0.01]).
Conclusions
Among women with pre-existing mental disorders who use hormonal contraceptives, we reported protective association with decreased depressive symptoms. However, the study also draws attention to some potential negative effects, including an increase in the risk of depression and antidepressant use among contraceptive users, a risk that is higher among women who use the hormonal IUD, implant, or patch/ring methods. Providers should select contraceptive methods taking individual aspects into account to maximize benefits and minimize risks.
... Building on previous research, in the present studies we sought to directly explore the relation between OC use and self-control. We focused specifically on OC use rather than the broader category of hormonal contraceptive use because 1) as we noted, OCs are the most commonly used hormonal contraceptive (16), and 2) oral delivery of exogenous hormones could be associated with different metabolic and cognitive effects than other delivery methods (30). Importantly, as the present investigation is one of the first to directly examine the relation between OC use and self-control, we aimed to simply determine whether OC use and self-control are correlated with one another, leaving issues of causality to be addressed by future studies. ...
In two studies we examined the relation between oral contraceptive (OC) use and self-reported levels of self-control in undergraduate women using OCs (Study 1: OC group N = 399, Study 2: OC group N = 288) and naturally cycling women not using any form of hormonal contraceptives (Study 1: Non-OC group N = 964, Study 2: Non-OC group N = 997). We assessed the self-overriding aspect of self-control using the Brief Self-Control Scale (BSCS) and strategies for self-regulation using the Regulatory Mode Scale (RMS), which separately measures the tendency to assess one’s progress towards a goal (assessment), and the tendency to engage in activities that move one towards an end goal (locomotion). In Study 1, we found no significant differences between OC and non-OC groups in their levels of self-overriding or self-regulatory assessment. However, we found that those in the OC group reported significantly greater levels of self-regulatory locomotion compared to those in the non-OC group, even after controlling for depression symptoms and the semester of data collection. The findings from Study 2 replicated the findings from Study 1 in a different sample of participants, with the exception that OC use was also related to higher levels of assessment in Study 2. These results indicate that OC use is related to increases in self-regulatory actions in service of goal pursuit and perhaps the tendency to evaluate progress towards goals.
... Previous consideration of androgenic effects of contraceptives such as oily skin, acne [1], hirsutism, android obesity, androgenic alopecia, unfavourable lipid profiles, diabetes and hypertension, has tended to focus on the direct androgenic effects of the exogenous progestins [2] rather than secondary effects on endogenous androgens. Minimizing androgenic side-effects is considered a key factor in the acceptability and continuation of hormonal contraception [3]. ...
Background
Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods.
Methods
In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant.
The primary outcome was free testosterone at 6 months.
Results
We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p < 0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference − 22.98, p < 0.001).
Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference − 50.04, p < 0.001 and than DMPA (mean percentage difference − 39.45, p < 0.001).
Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001).
Conclusions
This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study.
ECHO trial registration
ClinicalTrials.gov, number NCT02550067 15/09/2015.
Plain English summary
Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method.
Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users’ own circulating sex hormones, both the ‘female’ and the ‘male’ sex hormones (androgens).
In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years.
We measured the participants’ androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods.
This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.
... Su particular régimen cuadrifásico y la potente actividad uterotrópica explica su óptimo control del ciclo y sangrado de suspensión más breve, con mejores niveles de hemoglobina. Esta combinación VE/DNG, reduce sustancialmente la abundancia de flujo menstrual con respecto a otros AOC (9). ...
... La amenorrea inducida por cualquier método es beneficiosa para el tratamiento de la dismenorrea. Los anticonceptivos orales (especialmente las píldoras con progestágenos uterotrópicos) son particularmente eficaces contra la dismenorrea porque reducen el espesor y maduración del endometrio, disminuyen el flujo menstrual, inhiben la producción de prostaglandinas, e interfieren con la acción enzimática de la ciclooxigenasa 2, con una disminución subsiguiente de la presión y contractilidad uterina (3,9). ...
... Our results confirm the anti-androgenic effect of OHC with cyproterone acetate, as we found a statistically significant decrease in free testosterone and an increase in SHBG [22][23][24][25][26]. Since these are hormones that regularly follow the same patterns of concentration changes in various endocrinological diseases and dysfunctions, it can be assumed that similar patterns in the changes in the concentrations of DHEAS and total testosterone after OHC could also be shown in a larger sample. ...
... The increase in SHBG concentration was relatively expected considering the already mentioned inhibition of the hypothalamus-pituitary-ovary feedback loop and is comparable to other studies [24,25,27,28]. The increase in SHBG concentration, which leads to a decrease in free androgens concentration and a drop in testosterone concentration, is a consequence of the estrogenic component of OHC. ...
Aim: To investigate the effects of three-month use of oral hormonal contraception (OHC) on hormonal status and ovarian reserve indicator (anti-Müllerian hormone, AMH) in patients with polycystic ovary syndrome (PCOS). Methods: 19 patients with diagnosed PCOS and clinical and laboratory signs of hyperandrogenism without additional comorbidities and co-medication were included in the study. All participants received therapy with the same oral hormonal contraceptive (fixed combination of 0.035 mg ethinyl estradiol and 2 mg cyproterone acetate). The main outcomes were the concentrations of reproductive hormones measured before starting therapy and in the first cycle following therapy. Hormone concentrations were analysed using the immunochemical electrochemiluminescence (ECLIA) method. Results: Initial concentrations of total and free testosterone and AMH were elevated, while initial concentrations of other reproductive hormones were within reference values. By applying the therapy, the concentrations of AMH, luteinizing hormone (LH) and estradiol decreased by more than 20% and those of free testosterone by 85%. The concentration of sex hormone binding globulin (SHBG) increased by 44%. Conclusions: Three months of oral hormonal contraception with 35 μg ethinyl estradiol and 2 mg cyproterone acetate reduced elevated concentrations of AMH and free testosterone in PCOS patients. The decrease in serum AMH concentration indicates a temporary interruption of folliculogenesis as well as the selection of follicles from preantral to antral, and the decrease in androgens has a positive effect on the clinical condition and symptoms of patients with PCOS.
... Several types of progestins exist, each with its own unique chemical structure and pharmacological properties: first-generation progestins (norethisterone, lynestrenol, norethynodrel), second-generation progestins (levonorgestrel, norgestrel), third-generation progestins (desogestrel, gestoden, norgestimate), fourth-generation progestins (drospirenone, dienogest). Each progestin can have varying degrees of androgenic, estrogenic, and antiandrogenic properties, which can influence their specific applications in different medical treatments (De Leo et al., 2016;Sitruk-Ware, 2004). For example, progestins with higher androgenic activity may lead to side effects such as acne, hirsutism (excessive hair growth), and other androgen-related symptoms (Darney, 1995;Jones, 1995;Sitruk-Ware and Nath, 2013). ...
... Within the realm of OC, two major types are prescribed: progestinonly oral contraceptives (POC) and combined oral contraceptives (COC) (De Leo et al., 2016). COC, commonly known as the "micropill," contain both EE and progestins and are taken following a 21-day cycle with a 7-day pause to mimic the natural menstrual cycle. ...
... Studies were included if they met all the following criteria: (1) published between 2000 and June 2022. In recent years, since ~2000, newer OC with reduced doses of synthetic estrogen, known for their decreased side effects, have been introduced and are now widely prescribed and utilized (De Leo et al., 2016;Sondheimer, 2008) (2) in English or German language (3) human study, (4) experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, longitudinal studies, prospective and retrospective cohort studies, case-control studies and cross-sectional studies comparing groups of women using no OC such as naturally cycling women or females on other HC with females using OC including COC and POC, (5) participants older than twelve years, (6) type of progestin and (7) (self-reported) clinically relevant symptoms of mental disorders measured with a formal psychological instrument, for example Beck Depression Inventory (BDI) (Beck et al., 2011) or the Symptom-Checklist-90 (SCL-90) (Derogatis and Unger, 2010), a diagnosis of a mental disorder, or psychotropic drug use. All in-and exclusion criteria for studies are completely presented in Supplementary Material 2. ...
... Estrogen options currently available in COCs include ethinylestradiol (EE), and the natural estrogens: estradiol valerate (E2V), 17-beta estradiol (E2), and estetrol (E4) [7]. Estrogens play an important role in COCs [7,8]. The most widely used estrogen in COCs is EE due to its good oral bioavailability (38-48%) compared to E2 (5%) [8]). ...
... Estrogens play an important role in COCs [7,8]. The most widely used estrogen in COCs is EE due to its good oral bioavailability (38-48%) compared to E2 (5%) [8]). It is 15 to 20 times more active than estradiol after oral administration. ...
... COCs with 20 mcg of EE were introduced as an option for individuals who could not tolerate 30-35 mcg and with the idea of reducing risks, mainly thromboembolic [4,5]. These reductions were possible thanks to the availability of gestagens with high anti-gonadotrophic activity and to new administration regimens [8,9]. ...
Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users.
Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety.
Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: ‘oral contraceptives’, ‘estroprogestins’ and ‘combined oral contraceptives’.
Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman.
Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.
... A recent study found a 10% lower median plasma PLP level in oral contraceptive users compared to non-users 27 , an observation in agreement with our results. Oral contraceptives with estrogens have been reported to reduce the level of several vitamins, including B6 and B2 [28][29][30][31] , however most of these studies were published more than 40 years ago when the level of estrogen in oral contraceptives were much higher 32 . The lower levels of B6 vitamin in oral contraceptive users have also been suggested to be due to tissue redistribution of PLP, rather than actual vitamin B-6 deficiency 27,28,30 . ...
Changes in kynurenine metabolites are reported in users of estrogen containing contraception. We have assessed kynurenines, vitamin B6, vitamin B2 and the inflammation markers, C-reactive protein (CRP) and neopterin, in healthy, never-pregnant women between 18 and 40 years (n = 123) and related this to their use of hormonal contraception. The population included 58 women, who did not use hormonal contraceptives (non-users), 51 users of estrogen-containing contraceptives (EC-users), and 14 users of progestin only contraceptives (PC-users). EC-users had significantly lower plasma kynurenic acid (KA) and higher xanthurenic acid (XA) levels compared to non-users. Serum CRP was significantly higher and negatively associated with both vitamin B6 and B2 status in EC-user compared to non-users. No significant differences in any parameters were seen between PC-users and non-users (p > 0.1). The low KA and high XA concentration in users of estrogen containing contraception resemble the biochemical profile observed in vitamin B6 deficiency. The hormonal effect may result from interference with the coenzyme function of vitamin B6 and B2 for particular enzymes in the kynurenine metabolism. KA has been suggested to be neuroprotective and the significantly reduced concentration in EC-users may be of importance in the observed increased risk of mood disorders among users of oral contraceptives.
... Hormonal contraceptives (HCs), which involve the administration of exogenous sex hormones that affect endocrine regulation of the female reproductive system [5,6], are used by a sizeable proportion of individuals in both general (~ 28-43%) [7,8] and athletic (~ 40-51%) [9][10][11] populations. HCs are classified according to the hormones employed; combined HCs have both oestrogenic and progestin components, whereas other HCs have a progestinonly component. ...
Background
Resistance exercise training is widely used by general and athletic populations to increase skeletal muscle hypertrophy, power and strength. Endogenous sex hormones influence various bodily functions, including possibly exercise performance, and may influence adaptive changes in response to exercise training. Hormonal contraceptive (HC) use modulates the profile of endogenous sex hormones, and therefore, there is increasing interest in the impact, if any, of HC use on adaptive responses to resistance exercise training.
Objective
Our aim is to provide a quantitative synthesis of the effect of HC use on skeletal muscle hypertrophy, power and strength adaptations in response to resistance exercise training.
Methods
A systematic review with meta-analysis was conducted on experimental studies which directly compared skeletal muscle hypertrophy, power and strength adaptations following resistance exercise training in hormonal contraceptive users and non-users conducted before July 2023. The search using the online databases PUBMED, SPORTDiscus, Web of Science, Embase and other supplementary search strategies yielded 4669 articles, with 8 articles (54 effects and 325 participants) meeting the inclusion criteria. The methodological quality of the included studies was assessed using the “Tool for the assessment of study quality and reporting in exercise”.
Results
All included studies investigated the influence of oral contraceptive pills (OCP), with no study including participants using other forms of HC. The articles were analysed using a meta-analytic multilevel maximum likelihood estimator model. The results indicate that OCP use does not have a significant effect on hypertrophy [0.01, 95% confidence interval (CI) [− 0.11, 0.13], t = 0.14, p = 0.90), power (− 0.04, 95% CI [− 0.93, 0.84], t = − 0.29, p = 0.80) or strength (0.10, 95% CI [− 0.08, 0.28], t = 1.48, p = 0.20).
Discussion
Based on the present analysis, there is no evidence-based rationale to advocate for or against the use of OCPs in females partaking in resistance exercise training to increase hypertrophy, power and/or strength. Rather, an individualised approach considering an individual’s response to OCPs, their reasons for use and menstrual cycle history may be more appropriate.
Registration
The review protocol was registered on PROSPERO (ID number and hyperlink: CRD42022365677).
... With advancements in managing patients with PCOS, emerging medications have been utilized, providing clinical specialists with a broader range of options. New OC preparations containing natural estrogens (estradiol valerate, estetrol) instead of synthetic EE are thought to have a lower impact on coagulation and fibrinolytic systems (De Leo et al., 2016). Novel antidiabetic medications, including glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, are also used to promote weight loss and prevent the development of prediabetes or diabetes (Conway et al., 2014). ...
Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic ovary syndrome (PCOS). However, unclear risk-benefit profiles jeopardize their appropriate clinical applications. This study aimed to quantitatively evaluate the effects of the aforementioned medications and to compare their risk-benefit profiles. Randomized controlled trials published until 14th March, 2022 were searched in PubMed and Embase. A model-based meta-analysis was developed to examine the time-effect profiles of each medication. The maximal percentage change of the effect (Emax) and time to achieve half of Emax (T50) were estimated. Primary outcomes included menstruation, hirsutism score, free androgen index (FAI), body mass index (BMI), insulin sensitivity, and lipid profiles. Overall, 200 studies (9,685 patients and 385 arms) were identified for modeling. OCs performed exceptionally well in improving menstruation (Emax: 149%; T50: 7.44 weeks), hirsutism score (Emax: 66.2%; T50: 26.2 weeks), and FAI (Emax: 75.7%; T50: 0.51 weeks). However, OCs elevated the triglyceride (TG) level (Emax: 12.6%; T50:1.19 weeks). After 12-week OC treatment, the TG level of approximately 30% of patients, whose baselines were normal, exceeded the reference limit. This suggested that OC-induced dyslipidemia should be routinely monitored. The maximal BMI-lowering effect of metformin was similar to that of placebo (Emax: 3.80%); however, metformin had a shorter T50 (6.67 weeks versus 12.9 weeks). Further, active lifestyle intervention plus placebo significantly decreased BMI (Emax: 8.78%). Adding metformin to active lifestyle intervention accelerated the BMI-lowering effect within 24 weeks, whereas with the extension of this addition beyond 24 weeks, BMI did not reduce further, which indicated that benefits were limited from this prolonged addition. AAs were less potent in reducing hirsutism score (Emax: 40.2% versus 66.2%) and FAI (Emax: 34.5% versus 75.7%) compared to OCs. OC plus metformin combined OC-derived androgen-suppressing effects and metformin-derived insulin-sensitizing effects, and partially relieved the OC-induced TG increase (Emax: 9.76%). Baseline dependency was found in most clinical responses, implying that pharmacotherapies tailored based on baselines achieved more clinical improvements. This study presents new quantitative evidence on pharmacotherapies for PCOS. Currently, long-term risk-benefit profiles and emerging therapies are inadequately reported and require more further research.
