Monophasic Oral Contraceptives Research Articles

Decreased submaximal oxygen uptake during short duration oral contraceptive use: a randomized cross-over trial in premenopausal women

Long-term oral contraceptive (OC) use is known to be associated with changes in haemostasis, cardiovascular dynamics, and carbohydrate and lipid metabolism. Less well documented are the short-term variations in cardiorespiratory responses to exercise during the menstrual cycle of OC users. In this study the short-term effects of the usage of OC on cardiorespiratory and ventilatory responses to submaximal exercise were examined. Ten women (age= 23 ± 3 years) on monophasic OC were tested at three different times during their ‘cycle’ : during menstruation, off OC use (off OC: days 2 –; 4), early on OC use (EOC: days 7 – 9) and late on OC use (LOC: days 19 – 21). Times of testing were assigned randomly. On each occasion participants performed a continuous 12-min run exercise on a treadmill at three submaximal intensities (averaging 7, 8 and 9 km h−1), each for 4 min. Heart rate, ventilation ([Vdot]E), oxygen uptake ([Vdot]O2), carbon dioxide output ([Vdot]CO2), respiratory exchange ratio and running economy were assessed in the last minute of each stage of exercise. No significant variations were observed between the different times for heart rate, [Vdot]E, and [Vdot]CO2 irrespective of the stage of exercise (p > 0.05). Using two-way analysis of variance (ANOVA) with repeated measures on both factors (three stages and three times), [Vdot]O2 (ml kg−1 min−1) was lower by 3% to 5.8% when participants were on early and late OC use compared to off OC regardless of the stage of the exercise (F(2,18)= 6.3; p= 0.008). Running economy (ml O2 kg−1 km−1) was significantly improved (lower values) when women were on late OC use compared to off OC regardless of the stage of exercise. No significant interaction effect between stage of exercise and time of pill usage was demonstrated in any of the parameters studied. Results suggest that oral contraceptive users may expect lower [Vdot]O2 and better running economy during the pill ingestion phase and consequently have implications for exercise performances.

Oral Contraceptives Prior to Controlled Ovarian Hyperstimulation: Effect of Dose on the Timing of the Return of Ovarian and Pituitary Function During the Pill-Free Interval (PFI)

Objectives: The use of oral contraceptives (OCs) prior to controlled ovarian hyperstimulation (COH) allows for convenient cycle scheduling as well for ovulation suppression so that subsequent GnRH-agonist treatment cannot stimulate residual corpus luteum function. Although residual ovarian activity is known to exist during OC therapy, it is not clear how different OC formulations influence the degree of this suppression as well as the timing of the return of ovarian function when therapy is stopped. This question is important in the selection of an OC and in determining the optimal day for the initiation of COH. The objective of this study was to compare pituitary and ovarian activity during the seven day PFI among users of one of six different formulations of monophasic combined OCs.

Influence of the menstrual cycle phase and menstrual symptoms on maximal anaerobic performance

This study was designed to analyze the effect of the menstrual cycle phase on maximal anaerobic performance during short-term anaerobic tests. Seven eumenorrheic women (NOC) and 10 women using monophasic oral contraceptives (OC) performed three anaerobic tests (force-velocity, multi-jump, and squatting jump tests) during menstruation (M: between days 1 and 4), the midfollicular phase (F: between days 7 and 9), and the midluteal phase (L: between days 19 and 21) of the ovarian cycle. Follicular and luteal phases were confirmed by serum progesterone levels. The order of testing sessions was randomly assigned and a 15-min standardized warm-up preceded each testing session. Rectal temperatures were taken before (Trec(b)) and after (Trec(a)) warm-up. No significant differences were observed among M, F, and L in Trec(b), Trec(a) maximal cycling power (Pmax(c)), maximal jumping power (Pmax(j)), or maximal height of jump (h(j)) in either NOC or OC. Ten of the women suffered premenstrual or menstrual symptoms (MS); the other seven did not report any premenstrual or menstrual discomfort (NMS). Presence or absence of symptoms was not correlated with oral contraceptive use. No significant differences were observed among the three stages of the menstrual cycle in Pmax(c), Pmax(j), or h(j) in NMS. In MS, only Pmax(j) decreased by 8% in M compared with that in F (P < 0.05). Although there were no significant differences in maximal anaerobic performance during different menstrual cycle phases, results of this study suggest that the presence or absence of premenstrual or menstrual syndrome symptoms may have an effect, possibly through an action on the stretch-shortening cycle of tendons and ligaments.

Renewed Interest in Haemostasis Changes Induced by Oral Contraceptives (OCs)

Oral contraceptives (OCs) are used by millions of women and have proven to be very effective in contraception. To a large extent as a consequence of the cardiovascular side effects, in recent years the oestrogen concentration has been reduced and the type of progestagen has been changed. The more recent OCs are presently referred to as second and third generation, for which however the definitions are not uniform. Most commonly the second generation refers to OCs with approximately 30-35 µg ethinyloestradiol and the progestagen levonorgestrel, and the third generation to OCs with the progestagens desogestrel or gestodene and sometimes also norgestimate. Monophasic and multiphasic OCs are frequently not distinguished.

Influence of Menstrual Cycle Phase and Oral Contraceptive Use on the Time-of-Day Effect on Maximal Anaerobic Power

This study was designed to analyse the time-of-day effect in maximal anaerobic power, and the influence of menstrual cycle phase and oral contraceptive use on any diurnal effect. Diurnal variations in maximal cycling power were studied in 11 eumenorrheic women and 10 women using monophasic oral contraceptives. Subjects were tested at 09:00, 14:00 and 18:00 hours, assigned randomly on separate days, in the mid-follicular or pseudo-follicular phase (days 7, 8, 9) and in the mid-luteal or pseudo-luteal phase (days 19, 20, 21) of the menstrual cycle. The order of test sessions was randomly assigned. Body mass was measured before, and rectal temperature after, a standardized 15-min warm-up. Maximal cycling power (Pc) was determined by a force-velocity test. Rectal temperature significantly increased from morning (09:00) to afternoon (14:00 and 18:00) in follicular and luteal phases for eumenorrheic subjects, and in days 7–9 and days 19–21 for contraceptive users (p < 0.05). No significant interaction effects (time of day × group × cycle phase) were observed for rectal temperature. In eumenorrheic subjects, Pc increased significantly from 09:00 to afternoon during the follicular phase (P < 0.05). In contrast, no significant time-of-day effects were observed during the luteal phase in eumenorrheic subjects, and at any cycle phase in contraceptive users. Analysis of variance failed to reveal any significant interaction effects for Pc. This study suggested that the time-of-day effect on maximal anaerobic power could be damped during the luteal phase of eumenorrheic women or at any cycle phase by oral contraceptive use.

An open label, randomized study to evaluate the effects of seven monophasic oral contraceptive regimens on hemostatic variables: Outline of the protocol

Complementary to the epidemiological knowledge on the association between oral contraceptive use and the occurrence of venous thromboembolism, a study was designed to obtain more conclusive data regarding the effect of estrogen dose and progestogen type of oral contraceptives on risk markers for the occurrence of venous thromboembolism. The protocol for this multicenter, randomized, open label, parallel group, comparative study is outlined in the present article. A total of 730 healthy, nonsmoking, nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested in this study. The effects of progestogen type (desogestrel, gestodene, levonorgestrel, and norgestimate) and the effects of ethinyl estradiol dose (50, 30, and 20 μg) on various hemostatic variables was assessed, including the key components of the anticoagulant and fibrinolytic system, as well as the coagulation system. The primary outcome variables in the study were prothrombin fragment 1+2 and d-dimer.

Clinical comparison of triphasic norgestimate/35 μg ethinyl estradiol and monophasic norethindrone acetate/20 μg ethinyl estradiol: Cycle control, lipid effects, and user satisfaction

This six-cycle, multicenter, open-label, randomized study compared the clinical experience of two low-dose oral contraceptives (OC): a triphasic OC containing norgestimate (NGM) and 35 μg ethinyl estradiol (EE) (Ortho Tri-Cyclen®) and a monophasic OC containing norethindrone acetate (NETA) and 20 μg EE (Loestrin® Fe 1/20). Cycle control, lipid and androgen profiles, and user satisfaction were studied in new-start OC users (ie, no prior use within 60 days). Breakthrough bleeding or breakthrough spotting (BTB/BTS) occurred in a significantly smaller percentage of NGM/EE users than NETA/EE users during each of six cycles (p ≤0.002). The incidence of BTB/BTS ranged from 3.7% to 13.5% for NGM/EE users and from 23.5% to 49.7% for NETA/EE users. Significantly fewer NGM/EE users than NETA/EE users experienced absence of menses at cycles 2 through 6 (p ≤0.003). The percentages of women having no menses at each cycle ranged from 0.9% to 4.7% for NGM/EE users and from 10.3% to 21.3% for NETA/EE users. NGM/EE users reported a significantly (p <0.001) higher level of satisfaction with their OC at the end of six cycles than did NETA/EE users, but there was no significant difference in compliance, discontinuation rates, or adverse events between the two groups. NGM/EE produced a significantly (p ≤0.001) greater beneficial effect on HDL-C, HDL 2, and apo A-I than did NETA/EE. No statistically significant treatment differences were found for total cholesterol, LDL-C, triglycerides, or apo-B. Both OC increased sex hormone binding globulin and decreased free testosterone, but NGM/EE had a significantly greater effect (p <0.009).

Effects of two monophasic oral contraceptives containing 150 mcg of desogestrel in combination with 20 or 30 mcg of ethinylestradiol on adolescent girls with oligomenorrhea and ovarian hyperandrogenism

Adolescent girls in the early years after their first menstruation are characterized by frequent irregular menstrual cycles and absence of ovulation, often associated with clinical signs of hyperandrogenism, including hirsutism and acne. Often in these adolescent girls, both the ovarian structure and endocrine characteristics do not allow to distinguish the disease from polycystic ovarian syndrome (PCOS) observed in adults.

A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 μg ethinylestradiol and either 2 mg chlormadinone acetate or 150 μg desogestrel

Objectives To determine the effect of two low-dose monophasic oral contraceptives containing either 2 mg chlormadinone acetate or 150 μg desogestrel on blood clotting and fibrinolysis.Methods In vivo markers of intravascular coagulatory and fibrinolytic activity were measured in 45 volunteers randomly assigned to a 6-month treatment with one of the two study preparations.Results During oral contraceptive use, the procoagulatory activity increased (increased prothrombin fragment 1+2), the anticoagulatory capacity changed (increased protein C activity, decreased activated protein C sensitivity, decreased protein S activity and decreased antithrombin III activity) and the fibrinolytic system was activated (increased concentrations of plasmin-antiplasmin complexes and d-dimer as well as total fibrin degradation products). There were no relevant differences between the two medication groups.Conclusion Our results demonstrate that both oral contraceptive preparations have comparable effects on the hemostatic system. There was a shift towards a new equilibrium of hemostatic activities, both coagulatory and fibrinolytic, at a higher turnover rate. Changes did not exceed the range of normal variation and were comparable to the published effects of other low-dose oral contraceptives. There was no evidence of a differential risk of deep vein thrombosis between the two preparations.

Cyproterone Acetate (CA) Versus a Continuous Low-Dose Monophasic Oral Contraceptive (OC) in the Treatment of Recurrent Pelvic Pain After Conservative Surgery for Symptomatic Endometriosis

Cyproterone Acetate (CA) Versus a Continuous Low-Dose Monophasic Oral Contraceptive (OC) in the Treatment of Recurrent Pelvic Pain After Conservative Surgery for Symptomatic Endometriosis

The Effects on Carbohydrate Metabolism of a 21-day Monophasic Oral Contraceptive Containing Levonorgestrel 100 mcg and Ethinyl Estradiol 20 mcg

After treatment with high dose oral contraceptives, alterations in carbohydrate metabolism including decreased glucose tolerance and increased insulin resistance have been described. The purpose of this study was to determine the effects of a monophase oral contraceptive preparation of levonorgestrel 100 mcg and ethinyl estradiol 20 mcg (LNG/EE 100/20) on carbohydrate metabolism. LNG/EE 100/20 was administered orally once daily for 21 days followed by placebo for 7 days. Glucose tolerance was evaluated with the use of a standard 3-hour glucose tolerance test (GTT after administration of a 75-g loading dose of glucose. The GTT was performed dUring the prestudy period between menstrual cycle days 17 and 26. Testing was repeated during the third and sixth treatment cycles between tablet days 15 and 21. Mean changes from baseline values in glucose and insulin were calculated for each collection time. Forty healthy women were enrolled at a single university outpatient center. Data were available for analysis for 15 subjects who had complete data through 6 cycles. Two subjects with abnormally high pretreatment insulin values were excluded from the analysis. Except for a small mean increase in the 30-minute glucose value at cycle 6, there were no statistically significant changes from baseline in glucose or insulin values for the remaining 13 subjects. These changes were not believed to be clinically important because all individual values remained within the normal range. The results of this study show that this preparation of LNG/EE 100/20 has no clinically important effects on carbohydrate metabolism.

A comparative randomized trial on the impact of two low-dose oral contraceptives on ovarian activity, cervical permeability, and endometrial receptivity

In a double-blind randomized study, the suppression of ovarian activity and anti-conceptive effects on the cervix and endometrium were assessed during administration of two low-dose monophasic oral contraceptives (20 μg ethinyl estradiol [EE], 500 μg norethisterone—Eve 20 ® [Grünenthal, Aachen, Germany]; 20 μg EE, 150 μg desogestrel—Lovelle ® [Organon, Munich, Germany]). One hundred eighteen healthy women (ages: 18–35 years) were studied in 10 investigation centers during medication with either Eve 20 (n = 59) or Lovelle (n = 59). During three treatment cycles, ovarian activity was evaluated by somographic determination of follicle-like structures (FLS) and by simultaneous assessment of serum endocrine profiles (gonadotropins LH and FSH, ovarian steroids estradiol [E 2] and progesterone [P]). While on either treatment, no ovarian activity (as judged by no FLS and/or reduced sex steroid levels) was found in 90.8% (Eve 20) and 97.2% (Lovelle) of all investigated cycles. Follicular activity or cyst formation were detected in 18 of 173 cycles (Eve 20) and in 5 of 175 cycles (Lovelle), respectively. Gonadotropin levels were suppressed (LH < 6 IU/L, FSH < 8 IU/L) in most treatment cycles (Eve 20 76.6% vs. Lovelle: 84.8%). Serum E 2 concentrations exceeding 0.1 nmol/L indicated residual follicular activity in 19.3% (Eve 20) versus 12.2% (Lovelle) of all cycles. As estimated by serum P levels over 5 nmol/L, ovulation had presumably occurred in 4.1% (Eve 20) versus 2.9% (Lovelle) of treatment cycles. However, when the sonographical and endocrinological data were combined, no ovulation was documented in any pill cycle. The quality and quantity of the cervical mucus was found to be minimal in the majority of women. Moreover, the endometrial layer was determined to be low by ultrasound during most pill cycles, indicating equally strong suppressive effects on endometrial receptivity by the two contraceptives. These observations suggest that ovarian activity is suppressed in the majority of cycles during use of low-dose contraceptives. This effect may mainly be mediated by pronounced suppression of serum gonadotropin levels. Strong anti-conceptive effects of these formulations on both cervical permeability and endometrial receptivity are additional factors ensuring the contraceptive efficacy of these formulations.

Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives.

Epidemiological studies have shown that women who use third-generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate have a higher risk of venous thrombosis than women who use second-generation OC containing levonorgestrel. It is also known that a mutation in factor V (factor V(Leiden)), which results in resistance to activated protein C (APC) and which is the most common cause of hereditary thrombophilia, potentiates the prothrombotic effect of OC. Effects of APC on thrombin generation in the plasma of women using OC were compared to the response to APC in non-OC users and in individuals that were heterozygous or homozygous for factor V(Leiden). The response towards APC was evaluated on basis of the ratio (APC-sr) of the time integrals of thrombin formation determined in the presence and absence of APC. Compared with women not using OC, women who used OC exhibited a significantly decreased sensitivity to APC (P<0.001), independent of the kind of OC used. Women who used third-generation monophasic OC were significantly less sensitive to APC than women using second-generation OC (P<0.001) and had APC-sr that did not significantly differ from heterozygous female carriers of factor V(Leiden) who did not use OC. Women who were heterozygous for factor V(Leiden) and used OC had APC-sr in the range of homozygous carriers of factor V(Leiden). Two women who started OC therapy had significantly elevated APC-sr within 3 d. Acquired APC resistance may explain the epidemiological observation of increased risk for venous thrombosis in OC users, especially in women using third-generation OC.

The effects of monophasic and triphasic oral contraceptives on ovarian function and endometrial thickness

Objective To analyze and compare the effects of seven low-dose oral contraceptives (OCs) on ovarian function and endometrial thickness.Methods Cross-sectional study of users of one of five monophasic OCs, one of two triphasic OCs and a control group of non-users. Ovarian function, endometrial thickness and serum hormone levels were monitored during days 10–12 and 16–18 of the cycle.Results Serum estradiol was suppressed in OC users to a greater degree during days 16–18 than during days 10–12, whereas serum progesterone during days 16–18 was in the anovulatory range with each preparation. Ovarian activity as measured by follicular size was lowest with desogestrel-containing OCs, whereas greater activity was seen with triphasic levonorgestrel/ ethinylestradiol and triphasic norgestimate/ethinylestradiol. Endometrial thickness in OC users was significantly smaller than in controls.Conclusions All preparations demonstrated profound suppression of ovarian activity and effectively prevented ovulation. Ovarian suppression with desogestrel/ethinylestradiol 150/ 20 did not differ from that of other OCs despite its lower ethinylestradiol content. The use of both triphasic OCs, having a relatively low progestogenic activity, was associated with a higher ovarian activity than that of the monophasic OCs.

Inhibition of follicular growth by two different oral contraceptives (monophasic and triphasic) containing ethinylestradiol and gestodene

Objective To evaluate the inhibition level of ovarian follicular growth produced by a triphasic oral contraceptive (OC) containing ethinylestradiol and gestodene vs. the level produced by a monophasic OC containing the same components.Methods A randomized, blind, cross-over trial was performed in a sample of 56 women. The follicular diameters were measured in 56 cycles under triphasic contraceptive treatment, and the other 56 under monophasic contraceptive treatment, using vaginal ultrasound. The statistical analysis was performed using the Student's t test.Results The mean follicular diameter under monophasic OC treatment was found to be 8.16 mm (standard deviation 4.5), and while under triphasic OC treatment was found to be 7.44 mm (standard deviation 2.8) (p > 0.05). In 17 out of 112 cycles (15%), a certain degree of follicular activity was found (follicular diameter more than 10 mm), 10 cycles under monophasic OC and 7 cycles under triphasic OC.Conclusions The triphasic OC provides good inhibition of follicular growth and excellent contraceptive efficacy.

Investigation of the influence of two low-dose monophasic oral contraceptives containing 20 μg ethinylestradiol/75 μg gestodene and 30 μg ethinylestradiol/75 μg gestodene, on lipid metabolism in an open randomized trial

An open comparison at a single center was performed in volunteers (n=58) randomly allocated to two treatment groups, one receiving tablets containing 20 μg ethinylestradiol (EE) + 75 μg gestodene, and the other 30 μg EE + 75 μg gestodene. The study consisted of three treatment-free precycles, followed by thirteen 28-day treatment cycles. Analysis of results revealed that there were no statistically significant differences between the two groups with regard to the plasma levels of HDL-cholesterol and its subfractions, LDL-cholesterol and apolipoproteins. There was, however, a trend toward a more favorable effect on HDL-cholesterol in the 20 μg EE group, where levels increased by 3% compared with the 30 μg EE group, where levels decreased by 9%. There was a statistically significant difference between the adjusted mean values of total triglycerides in the two groups in favor of the 20 μg EE group (+21%), compared with the 30 μg EE group (+64%) (p=0.029). Two serious adverse events were reported (lymphadenopathy and vertigo), but neither were considered to be causally related to either study medication. The formulation containing 75 μg gestodene and 20 μg EE was shown to be a reliable and well tolerated oral contraceptive, with a favorable lipid profile.

Pituitary function varies during different phases of the same cycle in women with ovarian hyperandrogenism treated with either continuous or cyclic monophasic oral contraceptives or a GnRH agonist.

Pituitary function varies during different phases of the same cycle in women with ovarian hyperandrogenism treated with either continuous or cyclic monophasic oral contraceptives or a GnRH agonist.

The role of triphasic levonorgestrel in oral contraception: a review of metabolic and hemostatic effects.

Epidemiological studies suggesting a possible association between the use of combined oral contraceptives and an increased risk of cardiovascular disease have led to extensive investigations into the effect of oral contraceptives on lipid and carbohydrate metabolism, and on hemostasis. Since this association was originally suggested, the steroid dose in oral contraceptives has been significantly reduced and new progestogens have been developed. Also, triphasic formulations have been introduced which offer a well-balanced estrogen/progestogen ratio, allowing a further reduction in the progestogen dose per cycle, and thus helping to minimize unwanted metabolic and hemostatic effects. The metabolic interactions of triphasic levonorgestrel, the first triphasic formulation to be introduced, have received particular attention. Lipid metabolism appears to be largely unaffected by triphasic levonorgestrel, most studies reporting no significant change in high- (HDL-C) or low-density lipoprotein-cholesterol (LDL-C) levels. Several studies have reported a decrease in the lipoprotein subfraction HDL2-C levels, but in most cases measurements of the LDL-C/HDL-C and apolipoprotein A-1/B ratios reveal no clinically significant effects. Concerning lipids, most studies suggest that triphasic levonorgestrel has less metabolic impact than the monophasic formulation. In common with all currently available oral contraceptives, triphasic levonorgestrel appears to have some effect on carbohydrate metabolism. The study results vary, however; some investigators have found an impairment of glucose tolerance, whereas others have not detected any significant effect. Compared with lipid and carbohydrate metabolism, fewer studies have investigated the effect of triphasic levonorgestrel on hemostasis. In common with all estrogen-containing oral contraceptives, levonorgestrel appears to stimulate some procoagulant activity, elevating the levels of factors VII and X, and fibrinogen. However, the effect of triphasic levonorgestrel appears to be balanced, with most studies reporting a corresponding increase in anti-coagulant-fibrinolytic activity. Although most of the studies reviewed here reported some statistically significant metabolic interactions, many authors comment that the changes are probably not clinically relevant in terms of an altered risk of cardiovascular disease. The true risk of vascular disease associated with modern low-dose oral contraceptives remains to be confirmed when sufficient epidemiological data eventually become available.

Contraceptive efficacy and safety of a monophasic oral contraceptive containing 150 μg desogestrel and 30 μg ethinyl estradiol: United States clinical experience using a “Sunday start” approach

To report on experience in the United States with a monophasic oral contraceptive (OC) containing 150 micrograms desogestrel and 30 micrograms ethinyl E2 (EE). The results of a multicenter evaluation of efficacy, cycle control, and safety over 6 months of exposure using a "Sunday start" regimen is evaluated. Multicenter. Open noncomparative study. Study subjects were a mean age of 25 years, and the majority were educated, nonobese, white, nulliparous, and previously had used OCs. A total of 809 women were exposed to study medication for a total of 4,096 cycles (equivalent to 341.3 women-years of use). Efficacy was excellent. One user-failure pregnancy occurred (Pearl index 0.32); there were no method-failure pregnancies. Study medication was well tolerated; 6.6% of the subjects discontinued treatment because of drug-related adverse events. The study medication exhibited no adverse effects on blood pressure, body weight, or laboratory variables. Cycle control was evaluated in 697 subjects. In a total of 3,640 cycles, the incidences of intermenstrual bleeding, breakthrough bleeding, breakthrough spotting, and absence of withdrawal bleeding were 9.8%, 1.7%, 8.1%, and 1.4%, respectively, indicating appropriate cycle control. Patient acceptability was high; seven subjects (1%) discontinued the study because of menstrual irregularity (metrorrhagia). The results of this study, comparable to those demonstrated in a recent European multicenter study, add further documentation to the published data on the safety, efficacy, cycle control, and acceptability of this monophasic desogestrel-containing combined OC using a "Sunday start" approach.

Primary infertility and oral contraceptive steroid use

To determine the association between combined monophasic oral contraceptive (OC) use and primary infertility. Case-control. Women serving as controls of the Cancer and Steroid Hormone Study. Women were 19 to 40 years of age at first conception or infertility diagnosis. Based on 24 consecutive months of unprotected intercourse without a recognized conception, 419 nulligravid women had primary infertility; controls were 2,120 fertile women. A calendar of each woman’s reproductive history was used to determine fertility status and contraceptive use before infertility diagnosis or first conception. Primary infertility. Combined monophasic OC use was associated with a lower frequency of primary infertility, particularly among younger (age 20 years) compared with older women (age 30 years) after adjusting for barrier method use and education. A similar association was found for duration of OC use. When adjusted for age at first conception or infertility and barrier method, both higher (> 50 μ g) and lower (≤ 550 μ g) estrogen dose use were associated with decreased risk of primary infertility. Combined monophasic OC use was associated with a lower frequency of primary infertility.