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Query: UMLS:C0027497 (nausea)
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In England, health providers conducted a prospective study of 150 consecutive women 14-43 years old who sought emergency hormonal contraception (EHC) (50 mcg ethinyl estradiol + 500 mcg norgestrel) at the genitourinary medicine clinic of The Royal London Hospital in the Whitechapel section of London. 50% had also used EHC in the past. 23% had experienced at least 1 induced abortion. The reasons for EHC use were contraceptive failure for 100 (66%) women, unprotected sexual intercourse for 48 (32%) women, and rape for 2 women. 93% of the women reporting contraceptive failure were using a condom during the index sexual intercourse. The remaining women recognized the possibility of failure of their oral contraceptives (e.g., concurrent use of an antibiotic and forgotten pill). 50 (33%) and 21 (14%) women returned to the clinic for follow-up within 1 month and 1-3 months of initial presentation, respectively. Nine of these women had attended the family planning advisory clinic. 3.3% of the 71 women who returned to the clinic were pregnant. 22 (31%) of the women who returned to the clinic reported side effects (10 nausea and vomiting, 9 nausea, 5 abdominal pain, 1 breast tenderness, and 1 a panic attack). More than 31% of returning women reported an abnormal period after using EHC. 51% of returning women said that their preferred future method of contraception would be condoms. 10% either had not yet decided to use contraception or were planning to become pregnant. Clinic staff screened only 13% of all 150 women for sexually transmitted diseases (STDs) within 1 month of unprotected intercourse. None of them had an STD. Six of the 150 women returned for a second EHC prescription within 3 months. These findings indicate the need for clinicians to address future contraceptive plans at the time of EHC prescription, since most women did not return for follow-up or family planning advice. They should also screen for STDs during this initial contact considering the high rate of unprotected intercourse.
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PMID:Emergency hormonal contraception usage in genitourinary medicine clinic attenders. 870 28

The objective of a double-blind randomized multicenter trial enrolling 60 women was to determine the suppressive effect on ovarian activity of 20 mcg ethinyl estradiol plus 75 mcg gestodene administered for 21 or 23 days. The sites were at the Department of Obstetrics and Gynecology, University of Manchester, UK, and the Institute for Sterility Treatment, Vienna, Austria. The 60 women were healthy volunteers 19-35 years old, and they were randomized with 30 subjects each entering the treatment phase for either the 21-day regimen or the 23-day regimen. A pre-treatment cycle, 3 treatment cycles, and a post-treatment period were monitored by ovarian ultrasound and by measurements of luteinizing hormone (LH), follicle stimulating hormone (FSH), 17-beta-estradiol, and progesterone every other day. Two women on the 21-day regimen forgot to take 1 pill each. Side effects were minor including breast tension, vomiting, nausea, acne, and weight loss or weight gain. Withdrawal bleeding commenced in the 23-day group 2 days later than in the 21-day group. The frequency of intracyclic bleeding decreased when progressing from treatment cycle 1 to 3. No ovulation and no luteinized, unruptured follicle were observed. After stopping the medication, spontaneous ovulations were observed in all volunteers in the 23-day regimen. Suppression of ovarian activity was more pronounced in the 23-day regimen. 17-beta-estradiol serum levels during the last 6 days of a cycle and during the first 6 days of the next cycle were significantly less (p 0.05) in the 23-day regimen. The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown. The observed differences in the 17-beta-estradiol levels and follicular development between the 21-day and 23-day preparations suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations.
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PMID:Shorter pill-free interval in combined oral contraceptives decreases follicular development. 884 82

The side effects of oral contraceptives (OCs) can be minimized by appropriate OC selection. Side effects or perceived side effects that manifest themselves physically--e.g., weight gain, breakthrough bleeding (BTB), nausea, headache, breast tenderness, mood swings, acne, and hirsutism--are the most common causes of premature discontinuation of oral contraception. The relative androgenicity of the progestin component of combination OCs has become an important differential in selecting OC formulations. Several studies have indicated that preparations with less androgenic potential can minimize some of the "physical" side effects and adverse metabolic effects traditionally associated with oral contraception. Acne and hirsutism, common pre-existing conditions that are clearly related to the androgenicity of the progestin component, can be eliminated or improved by use of OCs with low androgenic activity. Many women perceive that OCs cause weight gain; although weight gain is to some extent androgen related, most studies comparing low-androgenic OCs with medium- or high-androgenic preparations have found little or no change in weight regardless of formulation. BTB, which usually subsides within a few months, is related to the dose, potency, and ratio of the estrogen and progestin in the OC formulation. Low-estrogen-dose OCs (< or = 35 micrograms ethinyl estradiol [EE]) containing less androgenic progestins are associated with bleeding patterns as acceptable as older low-estrogen-dose formulations. The same analysis found that smoking cigarettes promotes BTB in women who use OCs. There is no convincing evidence that the use of one progestin or another is less likely to cause or exacerbate headache; however, changing preparations sometimes reduces the incidence. Women with persistent headaches during the pill-free interval may benefit from a longer cycle of OC treatment. Nausea and breast tenderness are primarily estrogen-related effects; if a women experiences persistent nausea, switching to an OC formulation containing 20 micrograms EE may be appropriate as long as the patient is cautioned that BTB is more likely. Mood changes are a common, highly subjective complaint whose relationship to OC use is hard to assess. Concerns about the potentially deleterious effects of combination OCs on lipid/lipoprotein and carbohydrate metabolism have been substantially diminished by new epidemiologic findings relative to cardiovascular disease as well as by the development of low-androgenic progestins. Formulations containing these progestins lower LDL cholesterol and increase HDL cholesterol; they do not affect carbohydrate metabolism as much as older, more androgenic formulations.
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PMID:OC practice guidelines: minimizing side effects. 916 75

Use of vitamin B-6 has been recommended for the treatment of side effects associated with combined oral contraceptive (OC) use. To evaluate this recommendation, a randomized, triple-blinded controlled trial of 124 women recruited from 2 health centers in Zacatecas, Mexico, was conducted. 62 women received 150 mg of vitamin B-6 daily for 30 days, while the remaining 62 received a placebo. All cases and controls were new or continuing users of an OC containing 30 mcg of norgestrel and 30 mcg of ethinyl estradiol. Women rated the severity of 6 common OC side effects (nausea, headache, vomiting, dizziness, depression, and irritability) on a scale from 0 to 3 at baseline and 30 days after admission. There was a decrease in the severity of all 6 symptoms in both groups. Although higher proportions of women in the vitamin B-6 group reported decreases in OC-related side effect severity between admission and the 30-day follow-up visit, these differences were appreciable only for headache and dizziness and none was statistically significant. No evidence of vitamin B-6 toxicity was observed. However, this study failed to substantiate a clinically important pharmacologic effect of vitamin B-6 on OC side effects.
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PMID:Effect of vitamin B6 on the side effects of a low-dose combined oral contraceptive. 917 57

A cross-sectional study involving 60 women from Sydney, Australia, and 99 women from Los Angeles, California (US), evaluated the impact of three different insertion regimens on the transient nausea associated with the contraceptive vaginal ring. The ring released 20 mcg of ethinyl estradiol and 1 mg of norethindrone acetate per day. 128 women completed the 6-month study, providing 831 woman-months of exposure. The one pregnancy recorded during the 6-month study occurred during the 7-day break between cycles 5 and 6. 53% of women experienced nausea in at least one cycle. No significant differences in side effects were noted based on insertion group: 1) early evening (5-7 p.m.); 2) late night (10 p.m. to midnight); and 3) early evening insertion, removal at bedtime, and reinsertion the next morning. In each insertion group, the incidence of nausea was greatly reduced (to 6-9%) in the second cycle of use. 9% of women experienced transient vomiting in the 24 hours after first insertion of a new ring. The remaining side effects--headache, dizziness, uterine cramps, breakthrough bleeding, weight gain, and expulsion--were rare and occurred with equal frequency in all three insertion groups. Women at both study sites expressed a high degree of satisfaction with the vaginal ring, primarily because of its convenience and effectiveness. Overnight soaking of the ring before first use has the potential to reduce the side effect of transient nausea, presumed attributable to the accumulation of ethinyl estradiol on the ring surface during storage.
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PMID:Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring. 940 4

The contraceptive efficacy, cycle control, and safety of a new low-dose oral contraceptive (OC) containing 20 mcg of ethinyl estradiol and 100 mcg of levonorgestrel were investigated in a multicenter clinical study involving 805 German women (average age, 25.6 years) and a total of 4400 treatment cycles. There was one case of method failure, yielding a Pearl index of 0.29. A regular withdrawal bleed occurred in 95.5% of all treatment cycles. Cycle length and the duration and intensity of withdrawal bleeding were not significantly altered by use of the low-dose OC. Spotting alone occurred in 12.4% of treatment cycles and breakthrough bleeding alone was reported in 4.5%; both symptoms occurred in 1.4% of cycles. Headache, breast tension, and nausea were reported by 17.3%, 11.0%, and 7.7% of women, respectively. Only 8.4% of women discontinued OC use due to adverse events. Finally, there were no clinically relevant changes in laboratory parameters, blood pressure, or body weight. Overall, these findings suggest that substantial reductions in the estrogen and progestogen doses of OCs do not compromise contraceptive efficacy or cycle control.
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PMID:A multicenter, uncontrolled clinical investigation of the contraceptive efficacy, cycle control, and safety of a new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel over six treatment cycles. 943 56

The contraceptive safety and efficacy of long-term use of the oral contraceptive Belara (30 mcg ethinyl estradiol and 2 mg chlormadinone acetate) were assessed in an open, noncontrolled phase III study. Of particular interest was the effect of the anti-androgenic activity of this formulation on clinical signs of androgenization. Belara was taken by 1655 German women (mean age, 25.9 years), for a total of 22,337 cycles. A total of 12 pregnancies occurred, yielding a theoretical Pearl index of 0.269 (95% confidence interval, 0.109-0.600). No withdrawal bleeding occurred in 1655 cycles (7.4%), while spotting was documented in 2565 (11.5%) and breakthrough bleeding in 786 (3.5%). After 12 cycles of use, acne on the face/neck improved in 64.1% of affected women and completely disappeared in 53.4%. Seborrhea improved after 12 cycles in 67.9% of affected women and was cured in 58.0%. Side effects included headache (37.4%), nausea (23.1%), breast tenderness (21.7%), and vaginal discharge (19.4%). Of the 62 serious adverse events reported by 59 women, only the 2 cases of deep venous thrombosis could be linked to Belara use. Overall, these findings suggest that Belara is a well-tolerated oral contraceptive with minor side effects comparable to those associated with use of other low-dose pills.
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PMID:Efficacy and safety of the new antiandrogenic oral contraceptive Belara. 958 37

A study supported by the World Health Organization's Task Force on Postovulatory Methods of Fertility Control compared the efficacy of the Yuzpe and levonorgestrel-only methods of emergency contraception (EC). Enrolled in this double-blind, randomized trial were 1998 women from 21 centers around the world who requested EC within 72 hours of unprotected intercourse. The pregnancy rate was 1.1% for levonorgestrel alone and 3.2% for the combined ethinyl estradiol-levonorgestrel regimen. The crude relative risk of pregnancy was 0.36 (95% confidence interval, 0.18-0.70) for levonorgestrel compared with the Yuzpe regimen. The former method prevented 85% of expected pregnancies, while the latter prevented only 57%. Finally, side effects such as nausea, vomiting, dizziness, and fatigue were significantly less common in the levonorgestrel group. Although these findings document the superiority of the levonorgestrel regimen for EC, the 0.75 mg tablets are not currently manufactured in the US.
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PMID:Combined oral contraceptives versus levonorgestrel for emergency contraception. 1062 86

A double-blind, randomized controlled trial conducted at 21 centers in 14 countries compared the effectiveness and side effects of the traditional Yuzpe method of emergency contraception (200 mcg of ethinyl estradiol and 1 mg of levonorgestrel divided into 2 equal doses) and levonorgestrel alone (2 doses of 0.75 mg each). 1955 women (979 in the Yuzpe group and 976 in the levonorgestrel group) completed the study. 42 women had subsequent pregnancies, although at least 4 women were pregnant at the time of treatment. The pregnancy rate was 1.1% (95% confidence interval [CI], 0.6-2.0) for the levonorgestrel group and 3.2% (95% CI, 2.2-3.5) for the Yuzpe regimen. The relative risk of pregnancy was 0.36 (95% CI, 0.18-0.70). Levonorgestrel prevented 85% of expected pregnancies while the Yuzpe method prevented only 57%. Efficacy increased when the regimen was initiated within 24 hours and decreased as the time after unprotected intercourse approached 72 hours. Women in the levonorgestrel group reported less nausea, vomiting, dizziness, and fatigue than their counterparts in the Yuzpe group. Overall, 57% of women started bleeding within 3 days of their expected menses and the mean duration of menses of 4.7 days in both groups. Results of this study support use of levonorgestrel alone as an alternative for emergency contraception.
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PMID:Levonorgestrel versus the "Yuzpe" regimen. New choices in emergency contraception. 1009 1

This study determines the ovarian effects, contraceptive efficacy, and effects on serum levels of norethindrone acetate (NET-Ac) and ethinyl estradiol (EE) among women using a single contraceptive vaginal ring (CVR) cyclically over a period of 1 year. A total of 60 women were enrolled and used the ring according to a schedule of 3 weeks "in" and 1 week "out." Assays of serum norethindrone acetate (NET-Ac) ethinyl estradiol (EE) levels were taken twice weekly in cycles 6, 9, and 13. Despite luteal activity in some cycles, no pregnancies were noted within the 12-month study period. Heavier body weight was associated with increased probability of luteal activity. Mean serum levels decreased over the last 3 months of CVR use, accounting for the increase in luteal activity and possible ovulations in cycle 13. Among women in Sydney, by contrast with women in the other centers, a difference in the effect on lipids was seen. However, the changes in lipid levels were very small. The side effects were a little different from those experienced by women using a combined pill. Nausea and vomiting were largely confined to early cycles and most common in the first days of the first cycle. Weight gain was also not a problem, although there was a small mean increase in body weight over the 12-month treatment period. This study indicates that use of a single CVR releasing EE and NET-Ac over a period of 12 months constitutes an acceptable, safe and effective contraceptive method.
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PMID:Efficacy, bleeding patterns, and side effects of a 1-year contraceptive vaginal ring. 1049 85


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