Ethinyl Estradiol; Norelgestromin

What it is

This is an adhesive skin patch containing two synthetic hormones: norelgestromin, a progestin, and ethinyl estradiol, an oestrogen. One patch is worn for a week, replaced weekly for three weeks, then one patch-free week. It delivers roughly 150 mcg of norelgestromin and 35 mcg of ethinyl estradiol per day. Because the hormones bypass the gut and liver on first pass, total ethinyl estradiol exposure over a cycle is about 60% higher than with a 35 mcg oral pill, although the peak concentration is about 25% lower.

What the research says

As contraception it works about as well as a pill when used as directed. In a 1,417-woman randomised trial the patch's overall Pearl Index was 1.24 pregnancies per 100 person-years versus 2.18 for the comparator pill, a difference that was not statistically significant, and compliance was better with the patch (88.2% versus 77.7% of cycles perfect). The trade-off is thrombosis. A Danish cohort of 1.6 million women found 9.7 confirmed venous thrombosis events per 10,000 exposure years on the patch versus 2.1 per 10,000 woman-years in non-users, a relative risk of 7.9, and about twice the rate seen with levonorgestrel pills. A US claims study found a comparable doubling (40.8 versus 18.3 per 100,000 woman-years). The current US label contraindicates the patch in women with a BMI of 30 kg/m2 or above.

Evidence grade: Well established.

How it works

Drug class: Combined hormonal contraceptive (oestrogen plus progestin) delivered through the skin; norelgestromin is the active metabolite of norgestimate

The patch releases a progestin (norelgestromin) and an oestrogen (ethinyl estradiol) through the skin into the bloodstream, which suppresses the pituitary hormones that trigger ovulation. Ovulation is the main thing it blocks, but it also thickens cervical mucus so sperm find it harder to get through, and thins the lining of the womb so implantation is less likely. (Source 1)

Boxed warning

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS and CONTRAINDICATED IN WOMEN WITH A BMI ≥ 30 kg/m 2 • Cigarette Smoking and Serious Cardiovascular Events Cigarette smoking increases the risk of serious cardiovascular events from hormonal contraceptive use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, CHCs, including Xulane, are contraindicated in women who are over 35 years of age and smoke [see Contraindications (4) and Warnings and Precautions (5.1) ] . • Contraindicated in Women with a BMI ≥ 30 kg/m 2 Xulane is contraindicated in women with a BMI ≥ 30 kg/m 2 . The risk of VTE may be greater with Xulane in women with a BMI > 30 kg/m 2 compared to women with a lower BMI. [see Contraindications (4) and Warnings and Precautions (5.1 )] .

(Source 2)

What it is used for

• A randomised trial against a pill found comparable efficacy (Pearl Index 1.24 versus 2.18, not significantly different) with better compliance, and the manufacturer's three phase 3 trials gave 1.07 pregnancies per 100 woman-years. Effectiveness appears lower in women weighing 198 lbs or more. Evidence: established. (Source 3)
• Cochrane found combined oral contraceptives reduce period pain (standardised mean difference -0.58, high-quality evidence), but the trials were of pills, not the patch. In the patch's own trials dysmenorrhoea was reported as an adverse reaction in 7.8% of users and was significantly more common than with the comparator pill, so evidence specific to the patch is not supportive. Evidence: limited. (Source 4)
• Cochrane found six combined oral contraceptives reduced facial acne lesions versus placebo, but no placebo-controlled trial of the patch for acne was identified, and acne was itself reported in 2.9% of patch users in the phase 3 trials. Evidence: limited. (Source 5)

Interactions

• St John's wort (Hypericum perforatum) (pharmacokinetic study): St John's wort induces the CYP3A4 enzyme that breaks down both hormones in the patch. A systematic review of four comparative studies found three showed more breakthrough bleeding, three showed reduced hormone exposure, and one showed follicular growth and probable ovulation. The practical concern is contraceptive failure. (Source 6)
• St John's wort (Hypericum perforatum) (label): The FDA label lists St John's wort among the enzyme inducers that may make hormonal contraception less effective and directs that a back-up method be used, continuing for 28 days after the inducer is stopped. (Source 7)
• Grapefruit juice (label): Grapefruit juice inhibits CYP3A4 and the label groups it with other CYP3A4 inhibitors that may raise blood hormone levels. Higher oestrogen exposure is what the label links to a higher risk of adverse reactions including venous thromboembolism. (Source 7)
• Vitamin C (ascorbic acid) and paracetamol/acetaminophen (label): Both may raise blood ethinyl estradiol levels, the label suggests by blocking the conjugation step that clears it. The size of the effect is not quantified in the label and we found no outcome study of it. (Source 7)
• Alcohol (pharmacokinetic study): A 54-woman pharmacokinetic study found oral contraceptive steroids did not change how fast alcohol was cleared, though women on them recovered motor function faster. Its authors concluded women taking oral contraceptive steroids should not attempt to drink more than usual. (Source 8)

Stopping it

• There is no withdrawal syndrome and no taper. The thrombosis risk the patch adds is not permanent: the label states the excess risk of thromboembolic disease gradually disappears after use stops. (Source 9)
• Ovarian function returns. One trial measured pituitary and ovarian hormones after stopping and found FSH, LH and estradiol, though suppressed during use, returned to near baseline within six weeks. (Source 10)
• Not all risk falls away at once. In the Danish breast cancer cohort, women who had used hormonal contraception for five years or more still had a higher risk after stopping than women who had never used it. For cervical cancer the pooled reanalysis found risk declined after use ceased and had returned to never-user levels by ten years. (Source 11)
• The label also warns that the venous thromboembolism risk is highest in the first year of use and when restarting after a break of four weeks or longer, so stopping and restarting is not risk-neutral. (Source 9)

What goes wrong

In a national cohort of 1.6 million Danish women, patch users had 9.7 confirmed venous thrombosis events per 10,000 exposure years, a 7.9-fold rate compared with non-users of hormonal contraception. (Source 12)

• Cohort study, Moderate certainty.
• Size: 1,626,158 women, 9,429,128 woman years, 3,434 confirmed first venous thrombosis events.
• Who: all non-pregnant Danish women aged 15-49 free of previous thrombotic disease or cancer, 2001-2010.
• How long: 10 years.
• Result: patch relative risk 7.9 (95% CI 3.5 to 17.7) versus non-users; 9.7 events per 10,000 exposure years versus 2.1 per 10,000 woman years in non-users. Versus levonorgestrel combined oral contraceptives the adjusted relative risk was 2.3 (1.0 to 5.2).
• Funding: not stated in the abstract (independent registry study)

Limit of this finding: One sentence in the recorded passage says the risk of venous thrombosis 'was increased' in women using subcutaneous implants, and gives 1.4 with a range of 0.6 to 3.4. That range includes 1, so the implant result is not statistically significant: the data fit no increase at all just as well as an increase, and the paper's own wording overstates it. The patch and vaginal ring figures quoted in this finding do not have that problem - their ranges stay well above 1.

the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10,000 exposure years were 9.7 and 7.8 events.

A US insurance-claims study with record confirmation found venous thromboembolism rates more than doubled on the patch compared with a norgestimate 35 mcg pill. (Source 13)

• Cohort study, Low certainty.
• Size: 49,048 woman-years of patch exposure versus 202,344 woman-years of norgestimate pill exposure.
• Who: US women in UnitedHealthcare claims data, April 2002 to December 2004.
• How long: about 3 years of claims.
• Result: incidence rate ratio 2.2 (95% CI 1.3-3.8); 40.8 per 100,000 woman-years on the patch versus 18.3 on the pill. Nested case-control odds ratio 2.4 (1.1-5.5). Myocardial infarction IRR 1.8 (0.5-6.8); no strokes among patch users versus 10 among pill users. The authors state that acute myocardial infarction and stroke occurred too rarely to ascertain precise risk estimates.
• Funding: not stated in the abstract (this programme of work was manufacturer-sponsored; a reviewer should confirm)

Limit of this finding: The doubled clot rate is the one result this study can carry. The heart attack and stroke counts behind it are tiny - three heart attacks on the patch against seven on the pill, and no strokes on the patch against ten on the pill - and the authors say plainly that "Acute myocardial infarction and stroke occurred too rarely to ascertain precise risk estimates." So do not read the zero strokes as the patch protecting against stroke, and do not read the 1.8 heart-attack figure as a real increase: with numbers that small either direction is compatible with the data.

There was a more than two-fold increase in the venous thromboembolism rate (incidence rate ratio 2.2, 95% confidence interval [CI] 1.3-3.8) among transdermal contraceptive system users (20 cases, 40.8 per 100,000 woman-years) compared with norgestimate-containing oral contraceptives users (37 cases, 18.3 per 100,000 woman-years).

A randomised pharmacokinetic comparison found ethinyl estradiol exposure from the patch was higher than from a 30 mcg oral pill and 3.4 times higher than from the vaginal ring. (Source 14)

• Blood level study, Low certainty.
• Size: a small open-label randomised crossover-style comparison of three products (participant number not given in the abstract)
• Who: healthy women synchronised on a combined oral contraceptive for 2-8 weeks beforehand.
• How long: 21 days of each treatment.
• Result: EE area under the curve in the NuvaRing group was 3.4 times lower than in the patch group (p < .05) and 2.1 times lower than in the pill group (p < .05); serum EE varied much less with the ring than with the patch or pill.
• Funding: not stated in the abstract (study of a manufacturer's vaginal ring; a reviewer should check for sponsor involvement)

Analysis of area under the EE concentration-versus-time curve (AUC) during 21 days of treatment showed that exposure to EE in the NuvaRing group was 3.4 times lower than in the patch group (p < .05) and 2.1 times lower than in the pill group (p < .05).

The current label states ethinyl estradiol exposure is about 60% higher with the patch than with a 35 mcg oral contraceptive, and links higher oestrogen exposure to venous thromboembolism risk. (Source 15)

• Official position, Certainty not rated.
• Size: not stated.
• Who: women using the patch versus oral contraceptives containing EE 35 mcg.
• How long: not stated.
• Result: EE AUC approximately 60% higher with the patch; peak concentration approximately 25% lower.
• Funding: regulatory label.

The Area Under the Curve (AUC) for ethinyl estradiol (EE) is approximately 60% higher in women using XULANE compared to oral contraceptives containing EE 35 mcg.

In the manufacturer's phase 3 trials the commonest adverse reactions were breast symptoms, headache, nausea and application-site problems, each affecting roughly one in five to one in six women. (Source 16)

• Official position, Certainty not rated.
• Size: 3,322 women with safety data across three phase 3 trials.
• Who: sexually active women aged 18 to 45, predominantly white (91%)
• How long: 6 or 13 cycles.
• Result: Breast symptoms 22.4%, headache 21.0%, application site disorder 17.1%, nausea 16.6%, abdominal pain 8.1%, dysmenorrhea 7.8%, vaginal bleeding and menstrual disorders 6.4%, mood, affect and anxiety disorders 6.3%, vomiting 5.1%, diarrhoea 4.2%, vaginal yeast infection 3.9%, dizziness 3.3%, acne 2.9%, migraine 2.7%, weight increased 2.7%, fatigue 2.6%, pruritus 2.5%.
• Funding: regulatory label summarising manufacturer trials.

Limit of this finding: Every woman counted in this table was using the patch - the label's table has no placebo or comparison group. So these percentages are how often each symptom was reported by patch users, not how much of it the patch caused. Headache, nausea, period pain and mood symptoms all occur in women using no contraception at all, and this table cannot separate the two. The randomised comparison against a pill, recorded separately here, is what shows which problems were genuinely more common on the patch.

Dysmenorrhea 7.8% Vaginal bleeding and menstrual disorders 6.4% Gastrointestinal disorders Nausea 16.6% Abdominal pain 8.1% Vomiting 5.1% Diarrhea 4.2% Nervous system disorders Headache 21.0% Dizziness 3.3% Migraine 2.7% General disorders and administration site conditions Application site disorder 17.1%

In the head-to-head randomised trial, application site reactions, breast discomfort and dysmenorrhoea were significantly more common with the patch than with the pill. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 1,417 women.
• Who: healthy adult women.
• How long: 6 or 13 cycles.
• Result: application site reactions, breast discomfort and dysmenorrhea significantly more common in the patch group; 1.8% (300/16,673) of patches completely detached.
• Funding: not stated in the abstract.

however, application site reactions, breast discomfort, and dysmenorrhea were significantly more common in the patch group.

Compared with women who had never used hormonal contraception, current or recent users had a 20% higher relative risk of breast cancer in a 1.8 million-woman Danish cohort, an absolute excess of 13 cases per 100,000 person-years. (Source 11)

• Cohort study, Moderate certainty.
• Size: 1.8 million women, 19.6 million person-years, 11,517 breast cancers.
• Who: Danish women aged 15 to 49 with no prior cancer, venous thromboembolism or infertility treatment.
• How long: mean 10.9 years.
• Result: Versus never-users of hormonal contraception: relative risk 1.20 (95% CI 1.14 to 1.26), rising from 1.09 (0.96-1.23) at under 1 year of use to 1.38 (1.26-1.51) beyond 10 years; absolute increase 13 (10 to 16) per 100,000 person-years, about 1 extra breast cancer per 7,690 women using hormonal contraception for 1 year.
• Funding: Funded by the Novo Nordisk Foundation.

The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.

Pooled individual data from 24 studies found cervical cancer risk rose with current oral contraceptive use and fell back to never-user levels about ten years after stopping. (Source 17)

• Meta-analysis, Moderate certainty.
• Size: 16,573 women with cervical cancer and 35,509 without, from 24 studies.
• Who: women worldwide, adjusted for number of sexual partners, age at first intercourse, parity, smoking and screening.
• How long: lifetime exposure histories.
• Result: relative risk 1.90 (95% CI 1.69-2.13) for 5 or more years' current use versus never use; ten years' use from age 20 to 30 estimated to raise cumulative incidence by age 50 from 3.8 to 4.5 per 1000 in more developed countries.
• Funding: not stated in the abstract (academic collaborative reanalysis)

10 years' use of oral contraceptives from around age 20 to 30 years is estimated to increase the cumulative incidence of invasive cervical cancer by age 50 from 7.3 to 8.3 per 1000 in less developed countries and from 3.8 to 4.5 per 1000 in more developed countries.

What the evidence supports

In a randomised trial against a combined oral contraceptive, the patch's Pearl Index was numerically lower than the pill's but not statistically different, and compliance was better. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 1,417 women (812 patch, 605 oral contraceptive)
• Who: healthy adult women of child-bearing potential at 45 clinics in the US and Canada.
• How long: 6 or 13 cycles.
• Result: overall Pearl Index 1.24 patch versus 2.18 pill; method-failure 0.99 versus 1.25 (P =.57 and .80). Perfect compliance in 88.2% of patch cycles versus 77.7% of pill cycles (P <.001).
• Funding: not stated in the abstract (trial of a manufacturer's product, open-label)

Overall and method-failure Pearl Indexes were numerically lower with the patch (1.24 and 0.99, respectively) vs the OC (2.18 and 1.25, respectively); this difference was not statistically significant (P =.57 and.80, respectively).

Pooled data from 45 studies found long-term protection against ovarian cancer from oral contraceptives, persisting more than 30 years after use stopped. (Source 18)

• Meta-analysis, Moderate certainty.
• Size: 23,257 women with ovarian cancer and 87,303 controls from 45 studies in 21 countries.
• Who: women worldwide, stratified by study, age, parity and hysterectomy.
• How long: follow-up more than 30 years after use ceased.
• Result: risk reduction 29% (95% CI 23-34%) per 5 years of use that had ceased under 10 years previously; 10 years of use estimated to cut ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100.
• Funding: not stated in the abstract (academic collaborative reanalysis)

In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100

What the evidence does not support

Pharmacokinetic study found no detectable effect of oral contraceptive steroids on how fast the body clears alcohol. (Source 8)

• Blood level study, Low certainty.
• Size: 54 healthy women aged 18 to 40.
• Who: light and moderate drinkers, with and without oral contraceptive steroids at 30/35 or 50 mcg oestrogen.
• How long: 6 hours after 0.9 g/kg ethanol.
• Result: no significant differences in mean peak plasma ethanol concentration, time to peak, AUC or rate of ethanol disappearance between any of six subgroups.
• Funding: not stated.

There were no significant differences between any of the six subgroups in mean peak plasma ethanol concentration, mean time to peak, mean AUC, or mean rate of ethanol disappearance.

Where the evidence is mixed

Across three 12-month trials the pregnancy rate was 1.07 per 100 woman-years, but pregnancies clustered in heavier women. (Source 19)

• Official position, Certainty not rated.
• Size: 3,330 women completing 22,155 cycles.
• Who: women aged 18 to 45 in North America, Europe and South Africa; 91% Caucasian.
• How long: 12 months.
• Result: pregnancy rate 1.07 (95% CI 0.60, 1.76) per 100 woman-years in women aged 18 to 35; 5 of the 15 pregnancies occurred in women weighing 198 lbs or more, who were under 3% of the study population.
• Funding: regulatory label summarising manufacturer trials.

the pregnancy rate in women aged 18 to 35 years was 1.07 (95% confidence interval 0.60, 1.76) per 100 woman-years of norelgestromin and ethinyl estradiol transdermal system use

For thrombotic stroke and myocardial infarction the patch estimate was raised but too imprecise to be conclusive, in the same Danish cohort programme. (Source 20)

• Cohort study, Low certainty.
• Size: 1,626,158 women, 14,251,063 person-years, 3,311 thrombotic strokes and 1,725 myocardial infarctions.
• Who: Danish women aged 15 to 49 with no history of cardiovascular disease or cancer.
• How long: 15 years.
• Result: transdermal patch relative risk 3.2 (95% CI 0.8 to 12.6) for thrombotic stroke and 0.0 for myocardial infarction; background rates 21.4 strokes and 10.1 myocardial infarctions per 100,000 person-years.
• Funding: Funded by the Danish Heart Association.

For transdermal patches, the corresponding relative risks were 3.2 (0.8 to 12.6) and 0.0, and for a vaginal ring, 2.5 (1.4 to 4.4) and 2.1 (0.7 to 6.5).

Where the research disagrees

Whether the patch carries a higher venous thrombosis risk than combined pills

• Lidegaard and colleagues, Danish national cohort (2012), national registry cohort, 1,626,158 women, 9.4 million woman years, diagnoses confirmed by at least four weeks of anticoagulation: Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) (Source 12)
• The FDA label for the patch (2026), regulatory position citing a general CHC frequency of 3 to 12 cases per 10,000 woman-years without separating the patch: Based on results from a few studies, there is some evidence that this is true for non-oral products as well. (Source 9)

How much

• Reference intake: Dosing is set by the prescriber, not by the reader. As a position, the FDA label describes a 28-day cycle: a new patch each week for three weeks, then a patch-free fourth week, with every patch applied on the same day of the week. (Source 21)
• Upper limit: No upper limit in the nutritional sense applies. The label's limit is categorical rather than numerical: it contraindicates the patch in women with a BMI of 30 kg/m2 or above, and states the patch may be less effective in women weighing 198 lbs (90 kg) or more. (Source 2)
• Studied: The randomised trial against an oral contraceptive used three consecutive 7-day patches followed by one patch-free week, for 6 or 13 cycles. (Source 3)
• Studied: The manufacturer's three phase 3 trials gave 3,330 women 22,155 cycles of the patch over 12 months. (Source 19)

A common belief, and what the research shows

The belief: A patch is gentler than a pill because the hormones do not go through your stomach.

What the research shows: Bypassing the gut raises oestrogen exposure rather than lowering it. The label states ethinyl estradiol AUC is about 60% higher with the patch than with a 35 mcg pill, and a randomised pharmacokinetic study found patch exposure higher than a 30 mcg pill's. The Danish cohort measured 9.7 confirmed venous thrombosis events per 10,000 exposure years on the patch against 2.1 per 10,000 woman years in non-users, about twice the rate with levonorgestrel pills, and a US claims study found the same doubling. What the patch does improve is adherence: 88.2% of cycles were used perfectly versus 77.7% with the pill.

Questions and answers

What is it?

It is a thin adhesive patch worn on the skin that contains two synthetic hormones, the progestin norelgestromin and the oestrogen ethinyl estradiol. One patch is worn for a week and changed on the same day each week for three weeks, followed by a patch-free week when a withdrawal bleed is expected. It is a prescription combined hormonal contraceptive, not a supplement. (Source 21)

What does it do in the body?

The two hormones suppress the pituitary signals that drive ovulation, so in most cycles no egg is released. They also change cervical mucus so sperm have more difficulty entering the uterus, and change the lining of the uterus so implantation is less likely. (Source 1)

Is it good or bad for you?

Both, and which dominates depends on the person. It prevents pregnancy about as well as a pill, with better adherence, and oral contraceptives of this class carry long-term protection against ovarian cancer. Against that, Danish national data put confirmed venous thrombosis at 9.7 per 10,000 exposure years on the patch versus 2.1 in non-users, and the label now contraindicates it at a BMI of 30 kg/m2 or above and in women over 35 who smoke. For most young non-smoking women the absolute risk stays small; for a smoker over 35, or someone with a clotting history, it is the wrong method. (Source 12)

How do you get more of it?

These are prescription-only synthetic hormones with no food or supplement source. The only documented ways blood levels rise are pharmacological: CYP3A4 inhibitors including grapefruit juice, and ascorbic acid or acetaminophen, which the label says may raise ethinyl estradiol concentrations. Higher oestrogen exposure is a risk, not a goal: the label ties it to a greater chance of adverse reactions including venous thromboembolism. (Source 15)

If it is harmful, what reduces it?

Removing the patch is all it takes, and clearance is quick compared with most drugs: one trial found pituitary and ovarian hormones returned to near baseline within six weeks of stopping. The excess clotting risk also fades - the label states it gradually disappears after use is discontinued - although the breast cancer signal in the Danish cohort persisted for a time in women who had used hormonal contraception for five years or more. (Source 9)

Why might someone be low in it or missing it?

Not applicable in the nutrient sense; no one is deficient in a contraceptive. Hormone levels can fall below the contraceptive range for practical reasons: a patch that detaches (about 2% detached completely and 3% partially in the trials), a missed patch change, or an enzyme-inducing drug or herb such as St John's wort, rifampicin or certain anti-seizure medicines, which the label says calls for a back-up method continued for 28 days after the inducer stops. (Source 7)

Which whole foods contain it or feed it?

No food contains norelgestromin or ethinyl estradiol. Food matters only through interactions: the label lists grapefruit juice as a CYP3A4 inhibitor that may raise hormone levels, and ascorbic acid, the vitamin C in food and supplements, as another substance that may raise ethinyl estradiol concentrations. Alcohol does not appear to change the hormones' handling, and a pharmacokinetic study found the hormones did not change alcohol clearance either. (Source 7)

What happens if you do not have it?

Without contraception, pregnancy is the outcome at issue. In US survey data the failure rate for all hormonal methods combined was 6% in the first year of typical use, while condoms were 13% and withdrawal 20%; with no method at all, roughly 85% of women conceive within a year. Some non-contraceptive effects are also lost: this class of drug carries long-term protection against ovarian cancer, estimated at a fall from 1.2 to 0.8 ovarian cancers per 100 users before age 75 after 10 years of use. (Source 22)

How can you test for it?

There is no routine blood test for the patch's hormones and no need for one; contraceptive adequacy is judged by correct use, not by levels. The label's own monitoring instruction is clinical: blood pressure checks and attention to warning signs of clotting. Ethinyl estradiol and norelgestromin concentrations can be measured in research settings, which is how the 60% higher exposure versus a 35 mcg pill was established, but no validated clinical test tells an individual whether she is protected. (Source 15)

References

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3. JAMA. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial.. 2001. PMID 11343482, DOI 10.1001/jama.285.18.2347. Read the source
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13. Obstetrics and gynecology. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users.. 2007. PMID 17267834, DOI 10.1097/01.aog.0000250968.82370.04. Read the source
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17. Lancet (London, England). Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies.. 2007. PMID 17993361, DOI 10.1016/s0140-6736(07)61684-5. Read the source
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22. Perspectives on sexual and reproductive health. Contraceptive Failure in the United States: Estimates from the 2006-2010 National Survey of Family Growth.. 2017. PMID 28245088, DOI 10.1363/psrh.12017. Read the source