Low-dose Combined Oral Contraceptives Research Articles

High-dose oral contraceptives induce hyperinsulinemia without altering immune activation in diet-induced obesity which persists even following a dietary low-fat diet intervention

Combined oral contraceptives (COCs) are known to cause weight gain and alter metabolic and immunological pathways. However, modifications in arterial or venous thrombotic risk profiles of women of reproductive ages on COC remain unclear. The study aimed at assessing the impact of COC on immune activation in diet-induced obesity. We further established whether the dietary intervention of switching from a high-fat diet (HFD) to a low-fat diet (LFD) attenuates immunological responses. Twenty (n=20) five-week-old female Sprague Dawley rats were randomly divided into two diet groups of HFD (n=15) and LFD (n=5) and were monitored for eight weeks. After eight weeks, animals in the HFD group switched diets to LFD and were randomly assigned to receive high-dose COC (HCOC) or low-dose COC (LCOC) for six weeks. Animals on HFD significantly gained weight and had a higher lee index when compared to the LFD group (p < 0.05). Moreover, the triglyceride-glucose index, insulin, and other metabolic parameters also increased in the HFD group compared to the LFD group (p < 0.001). Consistently, the levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), were elevated in the HFD group when compared to the LFD group (p < 0.05). Upon switching from a high-fat to a low-fat diet, insulin levels persistently increased in animals receiving HCOC treatment compared to the LFD and HFD/LFD groups (p < 0.05). Thus, in a rat model of HFD-feeding, short-term HCOC treatment induces long-term metabolic dysregulation, which persists despite dietary intervention. However, further studies are recommended to confirm these findings.

Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

КОНТРАЦЕПЦИЯ ПОСЛЕ АБОРТА: ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ

It is important to choose a combined oral contraceptive (COC) after an abortion operation, since the requirements for a contraceptive prescribed during this period have their own specifics. It is necessary to stop as many negative consequences for the woman's body caused by the termination of pregnancy and, in addition, to ensure maximum safety of the prescribed drug. The relevance of this topic is due to the need to choose the safest and most effective contraceptive. A study was conducted of the effect of monophasic low-dose COCs, which is a combination of 0.15 mg levonorgestrel and 0.03 mg eeinylestradiol 0.03 mg in each tablet (PlaniGenslevo) on the state of the body and endothelial function in 22 women of reproductive age using the drug for 3 months after an artificial abortion and belonging to the first category of acceptability of COCs. As a control, the results of a test with reactive hyperemia were evaluated in 22 healthy women aged 19 to 35 years. As a result of the study, there was no increase in body mass index, blood pressure, changes in metabolic parameters in the biochemical analysis of blood, as well as an increase in the duration of menstrual bleeding, the absence of intermenstrual bleeding, as well as breast swelling, headaches, dyspeptic phenomena and other adverse events that may be caused by taking COCs in women using Women's Left within 3 months. The conducted study demonstrated the absence of adverse events on the part of the body of women taking after abortion Plani Women left. In addition, there were no statistically significant changes compared to the control group in the results of the test with reactive hyperemia, reflecting the absence of endothelial dysfunction in women using the contraceptive Plani Women left, which can serve as confirmation of the absence of a negative effect of the drug on the cardiovascular system.

Эффективность и безопасность комбинированного контрацептива с хлормадинона ацетатом при обильных менструальных кровотечениях и дисменорее в реальной клинической практике

This article presents the results of the prospective study involving 70 patients of reproductive age with heavy menstrual bleeding (HMB) and dysmenorrhea, interested in reliable contraception. Objective. To study the safety and efficacy of the low-dose combined oral contraceptive (COC) containing chlormadinone acetate (CMA) for the treatment of dysmenorrhea and HMB in real clinical practice. Patients and methods. Among 90 women who sought a method of contraception, we identified a group of 70 patients aged 18–45 years (mean age = 31.0 ± 7.7 [95% CI 29.2–32.9]) with complaints for HMB (n = 23) and/or dysmenorrhea (n = 65): primary (n = 37) and secondary (n = 28). For contraception, COC containing 0.03 mg ethinyl estradiol and 2 mg CMA was recommended. After 3 months, the dynamics of the volume of menstrual blood loss, pain severity (according to the Numeric Rating Scale (NRS)), as well as the frequency of side effects were assessed. Results. Among 90 women of reproductive age, 70 (78%) had HMB and/or dysmenorrhea of varying severity. After 3 months of using a low-dose CMA-containing COC, 87% of patients with HMB showed a statistically significant decrease in menstrual blood loss (p &lt; 0.001); in 72% of patients, a significant decrease in pain severity was observed: mean NRS value before taking COC was 6.2 ± 2.1 [95% CI 5.7–6.7]), it decreased to 3.5 ± 1.8 [95% CI 3.0-3.9]) (p &lt; 0.001) after 3 months. There were no significant differences in efficacy between the groups with primary and secondary dysmenorrhea. Conclusion. The prevalence of HMB and dysmenorrhea in a random sample of women of reproductive age is consistent with the data of systematic reviews (26% and 72%, respectively). The results obtained in real clinical practice confirm the additional therapeutic efficacy of the low-dose CMA-containing COC in HMB and dysmenorrhea. The frequency and severity of side effects during the COC use do not depend on the initial body mass index, but with an increase in the waist-to-hip ratio, there is a tendency to reduce the chance of developing side effects of using COC, which corresponds to the data on the metabolic neutrality of chlormadinone. Key words: chlormadinone, heavy menstrual bleeding, dysmenorrhea

Effects of Combination Oral Contraceptives on Bone Mineral Density and Metabolism in Perimenopausal Korean Women.

ObjectivesA retrospective cohort study was conducted to evaluate the effects of combination oral contraceptives (COCs) on bone mineral density (BMD) and metabolism in perimenopausal Korean women.MethodsThe study subjects comprised two groups. The COC group included 55 women who took low-dose COC for at least one year to control vasomotor symptoms. Another 55 women who had annual checkups without history of COC use served as controls. BMD and bone turnover markers were assessed periodically.ResultsIn the control group, 12-month BMD values at the lumbar spine (LS) and total hip (TH) significantly decreased with a greater magnitude at LS, and bone resorption (BR) and formation (BF) markers increased concurrently with a larger change in BR. COCs increased BMD at LS after 12 months and prevented BMD decline at TH. Multivariable linear regression revealed a significant difference in LS BMD between groups at 12 months. In the COC group, there were significant negative correlations between baseline BMD and Z-score at LS and corresponding changes at 12 months. COCs did not alter BR markers, whereas BF markers were significantly decreased at 3 months. Group comparison at 12 months, as tested with adjusted linear regression, disclosed significant differences in both BR and BF makers.ConclusionsBone loss associated with activated bone turnover is evident during the menopausal transition, and COCs might prevent BMD decrease and suppress bone turnover markers in perimenopausal Korean women. Significant increase in LS BMD and decreases in BF makers suggest underlying mechanisms of greater impact on BF.

Papillary Thyroid Cancer-Promoting Activities of Combined Oral Contraceptive Components

Background: Thyroid cancer is more common in women at reproductive age, suggesting the relationship between its high-incidence and therapeutic use of hormonal medications, such as oral contraceptives (OCPs). The aim of this study was to identify the effect of low-dose combined OCP (LD-COC) on proliferation, apoptosis, and migration of human papillary thyroid cancer (PTC) BCPAP cell line. Materials and Methods: BCPAP cells were cultured and treated with the combination of 90nM levonorgestrel (LNG) and 20nM ethinylestradiol (EE) for 48 hours. Afterward, using 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay, the proliferation of the cells was measured. Apoptosis was determined by using a Caspase-3 ELISA kit. Migratory properties of combined LNG and EE were studied through wound scratch assay. The expression levels of pro-apoptotic factor BAX, anti-apoptotic factor Bcl2, and proliferation marker Ki67 were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting. Results: Upon treatment with the combination of LNG and EE, proliferation and migration of BCPAP cells were significantly enhanced. However, LNG and EE remarkably inhibited apoptosis of these cells. Furthermore, treating PTC cells with combined LNG and EE caused a marked increase in the expression of Bcl2 and Ki67 and a considerable decrease in BAX levels (P˂ 0.05). Conclusion: Our data linked the use of COCs and the progression and aggressiveness of PTC, suggesting the role of these hormonal compounds as promoting factors for PTC tumors. Despite these observations, further investigations will be required to fully establish the pathogenic impact of these medications on PTC. [GMJ.2020;9:e1648]

Papillary Thyroid Cancer-Promoting Activities of Combined Oral Contraceptive Components.

Background: Thyroid cancer is more common in women at reproductive age, suggesting the relationship between its high-incidence and therapeutic use of hormonal medications, such as oral contraceptives (OCPs). The aim of this study was to identify the effect of low-dose combined OCP (LD-COC) on proliferation, apoptosis, and migration of human papillary thyroid cancer (PTC) BCPAP cell line. Materials and Methods: BCPAP cells were cultured and treated with the combination of 90nM levonorgestrel (LNG) and 20nM ethinylestradiol (EE) for 48 hours. Afterward, using 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay, the proliferation of the cells was measured. Apoptosis was determined by using a Caspase-3 ELISA kit. Migratory properties of combined LNG and EE were studied through wound scratch assay. The expression levels of pro-apoptotic factor BAX, anti-apoptotic factor Bcl2, and proliferation marker Ki67 were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting. Results: Upon treatment with the combination of LNG and EE, proliferation and migration of BCPAP cells were significantly enhanced. However, LNG and EE remarkably inhibited apoptosis of these cells. Furthermore, treating PTC cells with combined LNG and EE caused a marked increase in the expression of Bcl2 and Ki67 and a considerable decrease in BAX levels (P˂0.05). Conclusion: Our data linked the use of COCs and the progression and aggressiveness of PTC, suggesting the role of these hormonal compounds as promoting factors for PTC tumors. Despite these observations, further investigations will be required to fully establish the pathogenic impact of these medications on PTC.

Oral contraceptive use, bone mineral density, and bone turnover markers over 12months in college-aged females.

The purpose of this study was to compare bone mineral density (BMD) and bone turnover markers between combined oral contraceptive (COC) and non-COC users over 12months. COC users (n = 34, age = 19.2 ± 0.5) and non-COC users (n = 28, age = 19.3 ± 0.6) provided serum at baseline, 6months, and 12months. C-terminal telopepetides (CTX) and pro-collagen type 1N-terminal propeptides (P1NP) were determined using ELISA. BMD was measured at the three time points using dual-energy x-ray absorptiometry (DXA). COC users had greater CTX than non-COC users at baseline (18.6 ± 8.2 vs. 13.8 ± 5.3ng/mL, P = 0.021) and 6months (20.4 ± 10.3 vs. 14.2 ± 8.5ng/mL, P = 0.018). Controlling for lean mass, groups were similar in BMD. Over 12months, non-COC users maintained BMD at the spine, while the COC users declined 2.2% in lateral spine BMD (0.773 ± 0.014 to 0.756 ± 0.014g/cm2, P = 0.03) and 0.7% in anterior-posterior spine BMD (1.005 ± 0.015 to 0.998 ± 0.015g/cm2, P = 0.069). Non-COC users increased in BMD of the whole body over 12months (P < 0.001) while COC users had no change. Women who began COCs within 4years after menarche had lower BMD at the hip and whole body. Women taking very low dose COCs (20 mcg ethinyl estradiol, EE) significantly declined in CTX, P1NP, and lateral spine BMD in comparison to participants using low dose COCs (30/35 mcg EE). College-aged women who did not use COCs increased BMD of the whole body, while COC users had elevated bone turnover, declines in spinal BMD, and lack of bone acquisition of the whole body over 12months. Young females who initiate COC use early after menarche may experience skeletal detriments.

Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study.

The association between low-dose combined oral contraceptives (COCs) and anticoagulation factors in Japanese women has been rarely studied. A total of 394 Japanese women with a new beginning cycle of COC use were enrolled, of whom 335 women visited the clinic within 4weeks after starting the first cycle of COC. Visits occurred in the active phase (272 women) and the placebo phase (63 women). Free protein S (PS) antigen and activity levels and antithrombin activity levels decreased significantly in both the active and placebo phase groups. Protein C (PC) activity levels increased significantly in both groups. Larger reductions in free PS antigen and activity levels occurred with COC comprising either 30µg ethinylestradiol/desogestrel or 20µg ethinylestradiol/drospirenone than that comprising 35µg ethinylestradiol/norethisterone. In four women with the Japanese-specific PS K196E mutation, mean PS activity was 65% before COC use and 57% during COC use, indicating further decrease with COC use. In conclusion, decreased antigen and activity levels of PS and antithrombin and increased activity levels of PC were observed even during the first cycle of low-dose COC use. The effects on PS and PC activities were also observed in the hormone-free interval.

A comparative study of norethisterone and combined oral contraceptive pill in the treatment of dysfunctional uterine bleeding

Background: A significant percentage of women in India suffer from dysfunctional uterine bleeding (DUB), which has a negative impact on physical and social life. Norethisterone and low-dose combined oral contraceptive (COC) pills are used in the treatment of DUB. Aim: The aim of this study was to compare the efficacy and safety of norethisterone and low-dose COC pills in reduction of blood loss in DUB. Materials and Methods: A prospective randomized interventional study was conducted with patients with DUB. Pretreatment pictorial blood loss assessment chart (PBAC) and hemoglobin in blood were obtained from patients. Then, Group I (n = 50) and Group II (n = 50) patients were provided treatment with norethisterone and low-dose COC pills, respectively. Posttreatment PBAC and hemoglobin level in blood was obtained after 6 months of treatment. Improvements in PBAC and hemoglobin level (difference between posttest and pretest value) were compared by unpaired t-test with α = 0.05. Results: Mean age of Group I and Group II patients was 28.62 ± 9.84 and 28.42 ± 10.08 years, respectively. Improvement in PBAC score in patients treated with norethisterone versus low-dose COC pill was −98.62 ± 7.82 versus −96.44 ± 8.74 (P = 0.19). Improvement in hemoglobin level in patients treated with norethisterone versus low-dose COC pill was 2.75 ± 1.06 gm/dL versus 2.71 ± 0.86 gm/dL (P = 0.84). Conclusion: Norethisterone and low-dose COC pills were found to be equally efficacious in reducing bleeding in DUB. Hence, any one of the drugs can be used in the treatment of DUB according to patients' profile. However, considering the side effects, low-dose COC pills may be a better choice.

Plasma Renin in Women Using and not Using Combined Oral Contraceptive

Abstract Backgroud: Recent studies show that women on combined oral contraceptives (COC) present abnormal fasting lipid profile, increased postprandial lipemia, plasma C-reactive protein (CRP) and blood pressure (BP) compared to women not on combined oral contraceptives. Plasma renin is one of the factors responsible for abnormal BP. Objectives: To assess plasma renin levels in women using or not using COC, the correlation between renin and CRP, as well as divergences in lipid profile. Methods: A cross-sectional study with apparently healthy women aged 20 to 30, eutrophic, irregularly active, and with fasting triglycerides < 150 mg/dL. The sample was stratified into two groups: the No Combined Oral Contraceptive Group (NCOCG), comprised of women who did not use any type of hormone contraceptive, and the Combined Oral Contraceptive Group (COCG) comprised of women on low-dose COC for at least one year. After a 12-hour fast, 5 ml of blood was collected for renin dosing and PCR. Data were analyzed by the t-Test and bidirectional Mann-Whitney Test, both with significance < 0.05. Results: We evaluated 44 women equally distributed between the groups, age 23 ± 1.2 years, BMI 21.0 ± 3.2 kg/m2. Median and interquartile deviation of renin in the NCOCG and the COCG were, respectively, 0.5 (0.1-1.0) and 3.0 (2-6) (p < 0.01). A positive correlation between PCR and renin (p < 0.01 and r = 0.68) was found. Conclusion: The plasma renin levels of women using COC were higher, with a strong correlation with CRP.

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives

ObjectiveThe objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. MethodsThis was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n=42) (20μg EE/150μg desogestrel), oral contraceptives 2 (n=66) (30μg EE/3mg drospirenone), and a control group (n=70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. ResultsAt study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. ConclusionAdolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Effect of low dose combined oral contraceptives on prothrombin time

A 35 females used low dose combination oral contraceptive were enrolled in addition to 20 age matched healthy females included as a healthy control group.PT was estimated in plasma of all subjects.It was found significantly prolonged PT in users when compared with nonusers,and the results indicated prolong PT in the first 2 years of drug used and the alteration of PT disappear with continuous used. The results demonstrated the effect of low dose combination oral contraceptives on PT.

A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception.

BackgroundCombined oral contraceptives (COCs) containing various progestogens could be associated with differential risks for venous thromboembolism (VTE).ObjectiveTo evaluate the comparative risks of VTE associated with the use of low‐dose (less than 50 μg ethinyl estradiol) COCs containing different progestogens.Search strategyPubMed and the Cochrane Library were searched from database inception through September 15, 2016, by combining search terms for oral contraception and venous thrombosis.Selection criteriaStudies reporting VTE risk estimates among healthy users of progestogen‐containing low‐dose COCs were included.Data collection and analysisA random‐effects model was used to generate pooled adjusted risk ratios and 95% confidence intervals; subgroup and sensitivity analyses assessed the impact of monophasic‐COC use and study‐level characteristics.Main resultsThere were 22 articles included in the analysis. The use of COCs containing cyproterone acetate, desogestrel, drospirenone, or gestodene was associated with a significantly increased risk of VTE compared with the use of levonorgestrel‐containing COCs (pooled risk ratios 1.5–2.0). The analysis restricted to monophasic COC formulations with 30 μg of ethinyl estradiol yielded similar findings. After adjustment for study characteristics, the risk estimates were slightly attenuated.ConclusionsCompared with the use of levonorgestrel‐containing COCs, the use of COCs containing other progestogens could be associated with a small increase in risk for VTE.

How to reduce the number of side effects produced by COCs and improve adherence: simple tips for practitioners

The frequency and severity of side effects induced by the use of combined oral contraceptives (COCs) are the most common causes of withdrawal (64.4%). Better adherence can be achieved through adequate counselling on the choice of contraception and use of extended-regimen low-dose COCs with estrogen component and natural hormones containing novel selective progestins (dienogest, drospirenone) with minimum side effects. The choice of vitamin and mineral supplements based on the relevant micronutrient disbalance in women using COCs and "quick starting" could also contribute to compliance with the chosen method of oral contraception.

Pharmacokinetic Interactions Between Mirabegron and Metformin, Warfarin, Digoxin or Combined Oral Contraceptives

Mirabeg ron is a selective β3-adrenoceptor agonist approved for the treatment of overactive bladder (OAB). Four phase 1 studies were conducted in healthy subjects to evaluate the potential for pharmacokinetic interactions between mirabegron and metformin, warfarin, digoxin, or a combination oral contraceptive (COC). Thirty-two male subjects received metformin (500mg twice daily) or mirabegron (160mg once daily) alone, in combination or with placebo. Twenty-four male and female subjects received single doses of warfarin (25mg) alone and in combination with mirabegron (100mg once daily). Twenty-five male and female subjects were administered digoxin (0.25mg) alone and in combination with mirabegron (100mg once daily). Thirty female subjects received low-dose COC containing ethinylestradiol (EE)/levonorgestrel (LNG) (30/150µg once daily) in combination with mirabegron (100mg once daily) or placebo. Pharmacokinetic parameters were determined by non-compartmental methods. Absence of a Pharmacokinetic interaction was concluded if the 90% confidence intervals (CI) of geometric least-squares means ratio of area under the curve (AUC) and maximum concentration (C max) were contained within the standard 80-125% no-effect boundaries. The effect of mirabegron on warfarin International Normalized Ratio (INR) was also assessed. Mirabegron increased digoxin AUC and Cmax by 27 and 29%, respectively, indicating that mirabegron is a weak inhibitor of P-glycoprotein (P-gp) in vivo. Co-administration of mirabegron did not affect the pharmacokinetics of metformin, warfarin, EE and LNG, or warfarin INR, except for a slight extension of the 90% CI for the C max ratio for metformin (lower limit 79%). Metformin decreased mirabegron AUC and C max by 21%. Most treatment-emergent adverse events were mild, and all resolved by study end. No dose adjustment of either drug is required when mirabegron is administered concomitantly with metformin, warfarin or COC. Patients receiving mirabegron with digoxin may require additional monitoring of digoxin concentrations with dose adjustments where necessary, due to its narrow therapeutic index.

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability.

Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period

BackgroundLow-dose combined oral contraceptives (COCs) can interfere with bone mass acquisition during adolescence. This study aimed to evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) over a 1-year period and to compare their data with those of healthy adolescents from the same age group not taking COCs.MethodsThis was a non-randomized parallel-control study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years, divided into COC users (n = 41) taking 20 μg ethinylestradiol/150 μg desogestrel and COC non-user controls (n = 26), were evaluated by bone densitometry examinations at baseline and after 12 months. Comparisons between the groups at the study onset were performed using the Mann–Whitney test with the significance level fixed at 5% or p < 0.05. Comparisons between the groups at the study onset and after 12 months were based on variations in the median percentages for bone mass variables.ResultsThe COC users presented with low bone mass acquisition in the lumbar spine, and had BMD and BMC median variations of 2.07% and +1.57%, respectively, between the measurements at baseline and 12 months. The control group had median variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC showed similar evolutions during the study in both groups. Statistical significance (p < 0.05) was seen for the BMC percentage variation between COC users and non-users.ConclusionsUse of a low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) was associated with lower bone mass acquisition in adolescents during the study period.Trial registrationRegistry Number, RBR-5h9b3c.

Ovulatory effects of three oral contraceptive regimens: a randomized, open-label, descriptive trial

ObjectiveThis study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive (COC) regimen that included only ethinyl estradiol (EE) during the traditional hormone-free interval (HFI) and two commercially available 28-day regimens, a 24/4 and a 21/7 regimen. Study designThe randomized, open-label, parallel-group descriptive study was conducted at two US sites. Healthy, reproductive-aged women (n=146) were randomized to one of three groups for three consecutive 28-day cycles, as follows: treatment 1 (n=39 completed): 21/7-active COC [21days of 150 mcg desogestrel (DSG)/20 mcg EE, followed by 7days of 10 mcg EE (DSG/EE+7days EE)], treatment 2 (n=39 completed): 24days of 3mg drospirenone (DRSP)/20 mcg EE, followed by 4 placebo (PBO)-pill days (DRSP/EE+4days PBO) and treatment 3 (n=42 completed): 21days of 100 mcg levonorgestrel (LNG)/20 mcg EE, followed by 7 PBO-pill days (LNG/EE+7days PBO). The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogland and Skouby (H/S) method. ResultsOvarian activity rate (H/S grade 4 or 5) was low for all three treatments: 0% [95% confidence interval (CI) 0–2.8] for DSG/EE+7days EE, 1% (95% CI 0.2–5.2) for DRSP/EE+4days PBO and 1% (95% CI 0–3.9) for LNG/EE+7days PBO. All three treatments showed similar suppression of serum progesterone, 17β-estradiol, follicle-stimulating hormone and luteinizing hormone levels. ConclusionsThe 21/7-active low-dose COC regimen (DSG/EE+7days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4days PBO) and 21/7 (LNG/EE+7days PBO) regimens. ImplicationsThe 21/7-active low-dose COC regimen (DSG/EE+7days EE) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 (DRSP/EE+4days PBO) and the 21/7 (LNG/EE+7days PBO) comparator regimens.

Efficacy of fennel and combined oral contraceptive on depot medroxyprogesterone acetate-induced amenorrhea: a randomized placebo-controlled trial

ObjectivesWe aimed to determine the efficacy of fennel and low-dose combined oral contraceptive (LD-COC) on inducing menstrual bleeding and method continuation in women using depot medroxyprogesterone acetate (DMPA) who had no menstrual bleeding within the previous 45 to 140 days. Study designIn this double-blind double-dummy trial, 78 married women referred to public health centers in Hamadan, Iran, who complained of menstrual cessation induced by DMPA were randomly assigned into fennel, LD-COC or placebo groups with an allocation ratio of 1:1:1. All participants received two fennel or placebo capsules and one placebo or LD-COC pill daily for 21 days. We evaluated menstrual bleeding using the Higham pictorial chart within 40 days following initiating intervention. Data were analyzed using chi-square or analysis of variance. ResultsThere was no loss to follow-up. Significantly more women in the fennel (73%) and LD-COC (81%) groups experienced menstrual bleeding compared to the placebo (19%) group [relative risk (RR) 3.1, 95% confidence interval (CI) 1.6 to 6.2; RR 4.2, 95% CI 1.9 to 9.4, respectively]. Mean amount of menstrual bleeding among those who experienced menstruation was significantly higher in the fennel group (21 cc) than both the LD-COC (14 cc) and placebo (12 cc) groups. Also, women using fennel (73%) and LD-COC (65%) were significantly more likely than those using placebo (31%) to have subsequent DMPA injection [RR 2.5 (95% CI 1.3 to 4.9) and RR 2.0 (95% CI 1.1 to 3.7), respectively]. ConclusionsFennel and LD-COC can resolve DMPA-induced amenorrhea and increase continuation rate of this contraceptive method.