Use Of Low-dose Oral Contraceptives Research Articles

Bone impact after two years of low-dose oral contraceptive use during adolescence.

Data regarding the use and effect of hormonal contraceptives on bone mass acquisition during adolescence are contradictory. The present study was designed to evaluate bone metabolism in two groups of healthy adolescents using combined oral contraceptives (COC). A total of 168 adolescents were recruited from 2014 to 2020 in a non-randomized clinical trial and divided into three groups. The COC1 group used 20 μg Ethinylestradiol (EE)/150 μg Desogestrel and the COC2 group used 30 μg EE/3 mg Drospirenone over a period of two years. These groups were compared to a control group of adolescent non-COC users. The adolescents were submitted to bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers, bone alkaline phosphatase (BAP), and osteocalcin (OC) at baseline and 24 months after inclusion in the study. The three groups studied were compared at the different time points by ANOVA, followed by Bonferroni's multiple comparison test. Incorporation of bone mass was greater in non-users at all sites analyzed (4.85 g in lumbar Bone mineral content (BMC)) when compared to adolescents of the COC1 and COC2 groups, with a respective increase of 2.15 g and loss of 0.43g in lumbar BMC (P = 0.001). When comparing subtotal BMC, the control increased 100.83 g, COC 1 increased 21.46 g, and COC 2 presented a reduction of 1.47 g (P = 0.005). The values of bone markers after 24 months are similar for BAP, being 30.51 U/L (± 11.6) for the control group, 34.95 U/L (± 10.8) for COC1, and 30.29 U/L for COC 2 (± 11.5) (P = 0.377). However, when we analyzed OC, we observed for control, COC 1, and COC 2 groups, respectively, 13.59 ng/mL (± 7.3), 6.44 ng/mL (± 4.6), and 9.48 ng/mL (± 5.9), with P = 0.003. Despite loss to follow-up occurring in the three groups, there were no significant differences between the variables in adolescents at baseline who remained in the study during the 24-month follow-up and those who were excluded or lost to follow-up. Bone mass acquisition was compromised in healthy adolescents using combined hormonal contraceptives when compared to controls. This negative impact seems to be more pronounced in the group that used contraceptives containing 30 μg EE. http://www.ensaiosclinicos.gov.br, RBR-5h9b3c. "Low-dose combined oral contraceptive use is associated with lower bone mass in adolescents".

Low-dose gonadotropin-releasing hormone agonist therapy (draw-back therapy) for successful long-term management of adenomyosis associated with cerebral venous and sinus thrombosis from low-dose oral contraceptive use

The patient was a 38-year-old nulligravida with a history of smoking. She presented to this hospital with dysmenorrhea and postmenstrual lower abdominal pain. Adenomyosis was diagnosed using ultrasound and magnetic resonance imaging. She was instructed to stop smoking and was administered low-dose OCs. CVST occurred 18 months later. OC therapy was halted, and only antiplatelet therapy was administered. After six months, her chief complaint symptoms intensified, therefore GnRHa draw-back therapy was administered after obtaining informed consent. No uterine enlargement was observed, and the abdominal pain resolved. During 2.5 years of therapy, her bone density levels remained within normal limits. CVST did not recur and no other thromboses were observed.

Vocal Range in the Speech of Users of Low-Dose Oral Contraceptives

The study aimed to investigate the vocal range of oral contraceptive (OC) users aged between 20 and 30 years. This is a cross-sectional study. Forty-eight women aged 20-30 years who used low-dose OCs and 24 age-matched women who did not use oral monophasic contraceptives (w/oOC) were enrolled. Acoustic analysis was performed using the Motor Speech Profile program, Model 4341 (Kay Elemetrics Corp). Data were analyzed using generalized estimating equation. In the w/oOC group, the highest vocal tones in the sentence uttered using exclamatory intonation were similar in the follicular phases of two cycles (F1: 289 ± 46 Hz; F2: 284 ± 61 Hz). In the luteal phase of the first cycle, the vocal tones were lower, whereas in the second cycle they were higher than the tones in both follicular phases (L1: 274 ± 42 Hz; L2: 291 ± 62 Hz) (P = 0.056). In the highest vocal tones of the same sentence uttered using exclamatory intonation, the OC group showed lower tones (284 ± 53 Hz) than the w/oOC group (298 ± 44 Hz) (P = 0.048). In the lowest vocal tones of utterances of joy, the OC group showed higher values (180 ± 39 Hz) than the w/oOC group (169 ± 44 Hz) (P = 0.024). The close proximity of the highest to the lowest values of utterances of joy in the OC group (321 ± 59 Hz and 180 ± 39 Hz), when related to the w/oOC group (338 ± 65 Hz and 169 ± 44 Hz), suggests a reduced vocal modulation. The present findings demonstrate that the use of low-dose OCs influences the vocal range of women during menacme.

Low dose oral contraceptive use and the risk of thrombosis in polycystic ovary syndrome

Low dose oral contraceptive use and the risk of thrombosis in polycystic ovary syndrome

The use of low-dose oral contraceptives (OCPs) may be used effectively to treat dysmenorrhoea

The use of low-dose oral contraceptives (OCPs) may be used effectively to treat dysmenorrhoea

Effect of Reproductive Factors and Oral Contraceptives on Breast Cancer Risk inBRCA1/2Mutation Carriers and Noncarriers: Results from a Population-Based Study

Multiparity and breast-feeding reduce breast cancer risk, whereas oral contraceptive use may slightly increase breast cancer risk in the general population. However, the effects of these factors in BRCA1 and BRCA2 mutation carriers are less clear. Case patients were 1,469 women from Los Angeles County ages 20 to 49 years with newly diagnosed breast cancer. Control subjects were 444 women without breast cancer, individually matched to a subset of cases on race, age, and neighborhood. BRCA1/2 genes were sequenced in the cases, and odds ratios of breast cancer associated with various reproductive and hormonal factors in BRCA1/2 mutation carriers and noncarriers were estimated using multivariable logistic regression. Ninety-four women had a deleterious BRCA1 or BRCA2 mutation. Number of full-term pregnancies was inversely associated with breast cancer risk regardless of BRCA1/2 mutation status. Longer breast-feeding duration was protective among noncarriers but not among mutation carriers; however, this apparent effect modification was not statistically significant (P = 0.23). Neither oral contraceptive use overall nor the use of low-dose oral contraceptives was associated with an increased risk of breast cancer in any subgroup. Our results suggest that parity protects against breast cancer in BRCA1/2 mutation carriers, whereas breast-feeding does not. Our data suggest no association between oral contraceptive use and breast cancer risk in BRCA1/2 mutation carriers. Further confirmation that currently available low-dose oral contraceptives do not increase breast cancer risk in carriers is important from a public health perspective given the high prevalence of oral contraceptive use in the United States.

Oral Contraceptives and Breast Cancer–Reply–I

Oral Contraceptives and Breast Cancer–Reply–I

Migraine With Aura and Ischemic Stroke

See related article, pages 2438–2445. Migraine with aura has been consistently associated with increased risk of ischemic stroke.1–3 Most studies suggest that this association is particularly strong for younger women. Although several potential biological mechanisms have been proposed to explain the migraine-stroke association, the precise mechanisms remain unknown. Because migraine is particularly prevalent in an age group in which ischemic stroke, even among migraineurs with aura, is very rare, it seems likely that factors in addition to migraine with aura must be present to lead to an increased risk of stroke. In this issue of Stroke , MacClellan and colleagues4 evaluate several additional features that may help to identify patients with migraine with aura who are at particular increased risk of ischemic stroke. In this population-based case-control study of 386 women aged 15 to 49 with a first- ever ischemic stroke event and 614 age and ethnicity-matched controls, migraine and visual aura symptoms were ascertained using a standardized headache questionnaire. Participants could be classified into patients with probable migraine with visual aura (PMVA), probable migraine without visual aura, and patients without migraine. Compared with nonmigraineurs, …

Influence of endogenous and synthetic female sex hormones on human blood cells in vitro studied with comet assay

The comet assay has been conducted with numerous cell lines to assess in vitro genotoxicity. In order to use the comet assay as part of an in vitro test for evaluating genotoxicity, however, there are cell-specific factors that need to be better understood. In this present study we have evaluated some factors that may impact upon the DNA damage detected in whole blood (WB) cells and lymphocytes (ILs). Experiments were conducted comparing responses of both cells, and investigating the effects of the female hormonal cycle, and oral contraceptive (OC) use on DNA damage detection in the in vitro comet assay, at three sampling time. No significant differences were detected in the basal levels of DNA damage detected in ILs and WB cells from women OC users and non-users and from men. Basal DNA damage in ILs was unaffected by gender and stage of the menstrual cycle or the stage of the treatment schedule. Our results also indicated that the H 2O 2 induces DNA damage in human lymphocytes independently of gender, low-dose OC use and hormonal fluctuation. However, data showed that in 3rd sampling of menstrual cycle, lymphocytes were more resistant to H 2O 2-induced DNA damage than those from OC users and men.

Acceptability and satisfaction using Quick Start with the contraceptive vaginal ring versus an oral contraceptive

Background Many women discontinue their use of hormonal contraception, and even those who continue so may have difficulty using oral contraceptive pills consistently. New delivery systems, including the vaginal ring, may be easier to use, but user acceptability and satisfaction with these new methods may be affected by women's experience with their bodies. Materials and Methods Data for this study were collected as part of a randomized clinical trial on 201 women comparing immediate start of vaginal ring use with immediate start of low-dose oral contraceptive use. We assessed user satisfaction and method continuation 3 months after ring or pill initiation. Results At 3 months, 174 of 201 subjects (87%) had follow-up interviews. Among the 174 study participants with follow-up data, 61% of ring subjects and 34% of pill subjects were very satisfied with their methods (p=.003). For posttrial contraception, 79% of ring subjects chose to continue with the ring whereas 59% of pill subjects chose to continue with the pill (p<.001). Women who reported greater comfort in touching their genitals, greater frequency of masturbation, more comfort with intercourse and past use of vaginal contraceptives and products were not more likely than others to be satisfied with the ring or to continue using it for birth control. Conclusion Women who were allocated to vaginal ring use, regardless of their baseline characteristics or behavior, were likely to be highly satisfied with the method and to continue its use.

Prospective cohort study of the association between use of low-dose oral contraceptives and stroke in Chinese women

To clarify the association between use of widely distributed low-dose combined oral contraceptives (COCs) in China and the risk of stroke in order to decrease adverse reactions to COCs. A prospective surveillance cohort study was undertaken in 25 towns in two counties in Jiangsu Province, China. Women (44,408 ) on hormonal contraceptives (HC) and 75,230 women with an intrauterine device (IUD) were followed up from July 1997 to June 2000 to study the difference in the incidence of stroke. The incidence of haemorrhagic stroke (age- and county-standardised rate) was far higher than that of ischaemic stroke (34.74 vs. 11.25 per 100,000 person years) among HC cohort. The relative risk (RR) of incidence of haemorrhagic stroke in the HC cohort (52 cases) was 2.72 times compared with that in the IUD cohort (23 cases). Compared with IUD users, the current users of HC had a higher RR of 4.20 (95%CI, 2.11-8.36) of haemorrhagic stroke, and still reached 2.17 (95%CI, 1.16-4.06) among past users after they stopped taking COCs for more than 10 years. The RR of haemorrhagic stroke was 3.09 (95%CI, 1.26-7.57) among women who had last used low-dose COCs during the previous 5 years. In women aged less than 45 years, compared to IUD users, the haemorrhagic stroke was strongly associated with current use of low-dose combined norethisterone pills, with RR being 19.06 (95%CI, 3.08-118.03). There is an increased risk of haemorrhagic stroke among Chinese users of long-term low-dose oral contraceptives, which appears to persist long after discontinuation.

Association between the Current Use of Low-Dose Oral Contraceptives and Cardiovascular Arterial Disease: A Meta-Analysis

The long-term cardiovascular safety of widely used oral contraceptives (OCs) is still debated, and no meta-analysis assesses the modern use of OCs and the associated cardiovascular risks. We aimed to assess the risk of cardiovascular diseases associated with current use of low-dose combined OCs. All studies published between January 1980 and October 2002 were searched using MEDLINE, BIOSIS, and Scientific Citations. Original studies were selected independently by two investigators (J.P.B., P.A.E.) based on inclusion criteria: low-dose combined OC (<50 mug of ethinyl-estradiol); more than 10 cases in low-dose users; clear definition of cases; concurrent controls; and control for age. A third investigator (J.E.N.) adjudicated disagreements. From 2715 identified articles, 14 independent studies were included. All data were abstracted by one investigator (J.P.B.) in a systematic manner. Classification of OCs and types of exposure were directly abstracted from studies. Current use was defined as use at the time of the event or within 3 months. Only peer-reviewed studies with definition of events as definite or possible, based on prespecified criteria, were included. The summary risk estimates associated with current use of low-dose OCs were 1.84 [95% confidence interval (CI) = 1.38, 2.44] for myocardial infarctions and 2.12 (95% CI = 1.56, 2.86) for ischemic strokes. The overall summary odds ratio for both outcomes was 2.01 (95% CI = 1.63, 2.48). Second generation OCs were associated with a significant increased risk of both myocardial infarction and ischemic stroke events [1.85 (95% CI = 1.03,3.32) and 2.54 (95% CI = 1.96,3.28), respectively]; and third-generation OCs, for ischemic stroke outcome only [2.03 (95% CI = 1.15,3.57)]. In conclusion, a rigorous meta-analysis of the literature suggests that current use of low-dose OCs significantly increases the risk of both cardiac and vascular arterial events, including a significant risk of vascular arterial complications with third generation OCs.

Risk of ischemic stroke associated with low-dose oral contraceptive use: a meta-analysis

Risk of ischemic stroke associated with low-dose oral contraceptive use: a meta-analysis

Oral Contraceptives, Tubal Sterilization, and Functional Ovarian Cyst Risk

In Brief OBJECTIVE To determine whether current contraceptive method affects functional ovarian cyst risk, with emphasis on oral contraceptives (OCs) and tubal sterilization. METHODS We conducted a case–control study of 18–39-year-old health maintenance organization enrollees with a functional ovarian cyst diagnosed between January 1, and June 30, 1994, and age-matched female controls randomly selected from enrollment files. In-person interviews as well as medical and pharmacy records were obtained for 78% of cases and 82% of controls; these analyses were based on 392 cases and 623 controls. Odds ratios (ORs) calculated with unconditional logistic regression were used to estimate the risk of a functional ovarian cyst diagnosis associated with current contraceptive method. RESULTS In multivariable analyses adjusting for age, education, number of live births, and reference year, the overall OR was 0.72 (95% confidence interval [CI] 0.53, 0.99) for current OC use, compared with use of nonsurgical nonhormonal contraception or no contraception. The risk associated with use of 35 μg ethinyl estradiol monophasic OCs (OR 0.69; 95% CI 0.44, 1.10) was slightly lower than that associated with less than 35 μg ethinyl estradiol monophasic (OR 0.79; 95% CI 0.43, 1.47) or multiphasic OCs (OR 0.76; 95% CI 0.49, 1.19). Women with tubal sterilization had a substantially increased risk of a functional ovarian cyst diagnosis (OR 1.70; 95% CI 1.05, 2.75) compared with women using nonhormonal or no contraception. CONCLUSION Our findings suggest that low-dose OC use has little or no effect on functional ovarian cyst likelihood. The increased risks we found associated with tubal sterilization merit further investigation. Low-dose oral contraceptive use has little or no effect on functional ovarian cyst likelihood, whereas tubal sterilization is associated with substantially increased risk.

A meta-analysis on the correlation between ovarian activity and the incidence of intermenstrual bleeding during low-dose oral contraceptive use

A meta-analysis on the correlation between ovarian activity and the incidence of intermenstrual bleeding during low-dose oral contraceptive use

A survey on low-dose oral contraceptive transactions at pharmacies.

Low-dose oral contraceptives (OCs) were approved by the Japanese Ministry of Health, Labor and Welfare in 1999. However, few women use low-dose OCs (married 1.9%, unmarried 0.7%). A survey of pharmacies was conducted to determine the current status of OC transactions. Of the 449 pharmacies randomly selected from each prefecture in Japan, 408 agreed to be interviewed. The survey results indicated that few pharmacies (15.1% of the total) stocked low-dose OCs. Even among pharmacies where they were available, only a few (13.5%) offered a wide variety of low-dose OCs for immediate dispensing. The price of low-dose OCs varied widely (yen 1,167-yen 7,000). In many pharmacies, the amount of space and interior structure were not adequate for users to seek advice on and receive low-dose OCs. The survey revealed that the current environment of many pharmacies is not adequate for users to visit, consult on OC use, and receive their prescriptions. To promote wider use of low-dose OCs, the facilities of pharmacies as well as the behavior of pharmacists need to be improved to safeguard the privacy of users.

Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral contraceptive use in young women

With the aim to determine whether bone metabolism in young women using low-dose oral contraception is influenced by vitamin D receptor (VDR) genotype, we designed the prospective clinical study of 41 healthy women aged 20–27 years. Twenty-one women of the study group were prescribed an oral contraceptive (30 μg ethynyl estradiol and 150 μg levonorgestrel) and 20 women of the control group a nonhormonal contraceptive or none. Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline) and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the study group, the BB genotype subgroup showed significantly decreased osteocalcin (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p = 0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no changes were observed. In the control group, there were no significant changes in markers of bone metabolism regarding VDR genotype. In conclusion, our study shows that in young women VDR gene polymorphism could influence bone metabolism during low-dose oral contraceptive use.

Venous and arterial thrombosis during oral contraceptive use: risks and risk factors.

Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two- to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 microg to 20-30 microg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis.

A meta-analysis on the correlation between ovarian activity and the incidence of intermenstrual bleeding during low-dose oral contraceptive use

We aimed to evaluate potential correlation between ovarian activity during use of combined oral contraceptives and the incidence of intermenstrual bleeding. Data from seven prospective clinical studieswith five different combined low-dose oral contraceptives were retrospectively analyzed to determine ovarian activity measured by the Hoogland Score (follicle diameter and endogenous hormone levels) andcycle control. A total of 227 young fertile women were evaluated over three treatment cycles each. Women with intermenstrual bleeding had statistically significantly higher estradiol levels than those withoutintermenstrual bleeding. Also ,women with intermenstrual bleeding had significantly larger follicle-like structures than those without intermenstrual bleeding. For example ,in the second treatment cyclethe difference of the mean follicle diameters between women without intermenstrual bleeding (12.5 mm) and women with spotting (16.9 mm) or breakthrough bleeding (16.1 mm) was statistically significant (p= 0.0179). Less than 17% of women with Hoogland Score 1 ,2 or 3 (low ovarian activity) reported intermenstrual bleeding. On the other hand ,35.2% of women with Hoogland Score 4 (active follicle-like structures)reported intermenstrual bleeding. The association between bleeding and Hoogland Score was statistically significant (p < 0.0011). The findings of this retrospective analysis provide evidence that highovarian suppression is positively correlated with improved cycle control in terms of less frequent intermenstrual bleeding - slight and heavy.

Low-dose oral contraceptive use and the risk of myocardial infarction

Background Studies of oral contraceptives (OCs) containing 50 µg or more of estrogen suggest an increased risk of myocardial infarction (MI) among current users, particularly if they smoke heavily. Objective To assess whether use of the newer lower-dose OCs increases the risk of MI. Methods A case-control study was conducted from January 1985 through March 1999 in 75 hospitals in the greater-Boston and greater-Philadelphia areas. Data on OC use and MI risk factors were obtained by interview from 627 women with a nonfatal first MI (cases) and 2947 female hospital controls younger than 45 years. Results The overall odds ratio (OR) for current OC use relative to never used was 1.3 (95% confidence interval [CI], 0.8-2. 2). The OR was elevated, 2.5 (95% CI, 0.9-7.5), among heavy smokers (≥25 cigarettes per day) but close to 1.0 among lighter smokers (OR = 0.8) and nonsmokers (OR = 1.3). For current OC use together with heavy smoking relative to nonuse and nonsmoking, the OR was 32 (95 % CI, 12-81), considerably greater than that for heavy smoking alone, 12 (95% CI, 8.6-16). The ORs did not vary according to the type of formulation or the dose of estrogen; there were too few users to assess the new 20-µg preparations. Past OC use was unrelated to risk. Conclusion Current use of low-dose OCs in the United States is unrelated to an increased risk of MI among nonsmokers and light smokers, but users who smoke heavily may be at greatly increased risk.