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Research · Medication

Hormonal birth control

Pills, patch and ring failed in about 4.6 per 100 women a year in a US cohort, against 0.27 for IUDs and implants. Pills eased acne and period pain. Clots rose about threefold on levonorgestrel pills and more on newer progestins and the patch, still rare. Breast cancer rose slightly, ovarian and endometrial cancer fell, and fertility returned.

Add to Bio HackChecked 2026-11-13
Status
FDA-approved to prevent pregnancy. Most are prescription products in the US. Opill (norgestrel 0.075 mg) is sold over the counter. Some pills are also approved for moderate acne or premenstrual dysphoric disorder, and Mirena for heavy menstrual bleeding. Combined pill and patch labels carry a boxed warning about smoking and serious cardiovascular events.
Also called
birth control pill, the pill, combined oral contraceptives, COC, ethinyl estradiol, levonorgestrel, norethindrone, norgestimate, desogestrel, drospirenone, Yaz, Yasmin, Loestrin, Sprintec, progestin-only pill, mini-pill, Opill, Slynd, Camila, norgestrel, contraceptive patch, Xulane, Twirla, vaginal ring, NuvaRing, Annovera, implant, Nexplanon, etonogestrel, hormonal IUD, levonorgestrel intrauterine system, Mirena, Kyleena, Liletta, Skyla
Taken for
preventing pregnancy, acne, period pain, heavy periods, fibroids, PMDD, regular periods, lowering ovarian cancer risk, lowering endometrial cancer risk, high testosterone symptoms, PMS, endometriosis pain, PCOS

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help13

Reported risks12

What people take it for, and what was found

Shown to help13

LimitedStudied in women

Preventing pregnancy

Linked to 4.55 unintended pregnancies per 100 women a year on pills, patch or ring, against 0.27 on IUDs and implants, in a large US cohort.

Compared with IUDs and implants [1]; no comparison group in the label trials [2][3]

The numbers and sources
Effect
The failure rate was 4.55 per 100 participant-years on pills, patch or ring and 0.27 on long-acting methods (adjusted HR 21.8, 95% CI 13.7 to 34.9). Women under 21 on pills, patch or ring had almost twice the risk of older women [1]. In the label trial of drospirenone 3 mg with ethinyl estradiol 0.02 mg, the Pearl Index was 1.41 pregnancies per 100 woman-years [2]. In Mirena's extension, the cumulative pregnancy rate over years 6 to 8 was 0.68% [3].
Population
7,486 women given their choice of method at no cost in St. Louis [1]; 1,027 women aged 17 to 36 [2]; Mirena extension users [3].
Sources
[1], [2], [3]
Caveats
An observational cohort in which women chose their method [1]. Label trials have no control group.
ModerateStudied in women

Acne

Shown to reduce acne lesions and severity in women more than placebo, in all nine placebo-controlled trials with data, across several progestin types.

Compared with placebo, other combined pills and an antibiotic [4]

The numbers and sources
Effect
Every placebo-controlled trial found fewer acne lesions and lower severity. A levonorgestrel pill cut total lesions by about 10 (MD -9.98, 95% CI -16.51 to -3.45) and a norgestimate pill by 9.32. Clear or almost clear skin was more likely on a drospirenone pill (OR 3.02). Differences between progestins were less clear [4]. The drospirenone pill Yaz is FDA-approved for moderate acne in women who also want contraception [2].
Population
12,579 participants in 31 trials [4].
Sources
[4], [2]
Caveats
Data for any single comparison between pills were limited [4].
ModerateStudied in womenVery common

Period pain

Shown to reduce period pain in women more than placebo, with improvement in 37% to 60% against 28%, along with more irregular bleeding, headache and nausea.

Compared with placebo or no treatment [5]

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Combined pills reduced pain more than placebo (SMD -0.58, 95% CI -0.74 to -0.41, high quality) and raised the chance of improvement (RR 1.65), from 28% to between 37% and 60%. Extra medication and missed work fell (RR 0.63 each). Continuous pill use may reduce pain more than the standard regimen [5].
Population
3,723 women in 21 trials [5].
Sources
[5]
Caveats
The dichotomous pain result was low quality [5].
ModerateStudied in women

Heavy periods (hormonal IUD)

Shown to lower heavy menstrual blood loss more than other medicines, about 67 mL more, with fewer treatment failures, on the levonorgestrel IUD in women with heavy periods.

Compared with oral progestins, combined pills, mefenamic acid, tranexamic acid or usual medical treatment [6]; medroxyprogesterone acetate [3]

The numbers and sources
Effect
Against other medical therapy, the levonorgestrel IUD lowered menstrual blood loss (MD 66.91 mL, 95% CI 42.61 to 91.20, low certainty), led to fewer treatment failures (RR 0.34) and fewer withdrawals (RR 0.49), and slightly raised quality of life [6]. In the label trial, Mirena reduced blood loss more than medroxyprogesterone acetate over 6 cycles [3].
Population
2,511 women in 25 trials [6]; 160 women with blood loss of 80 mL or more [3].
Sources
[6], [3]
Caveats
Attrition bias and small numbers in several trials [6].
ModerateStudied in women

Heavy periods (combined pill)

Shown to return heavy periods to normal in 12% to 77% of women on the combined pill, against 3% on placebo. The hormonal IUD lowered blood loss more.

Compared with placebo, NSAIDs, the levonorgestrel IUD, the vaginal ring and long-course progestogens [25]

The numbers and sources
Effect
Against placebo, a combined pill with a step-down estrogen and step-up progestin regimen raised the odds of periods returning to normal (OR 22.12, 95% CI 4.40 to 111.12, 2 trials, 363 participants) and of lower blood loss (OR 5.15, 95% CI 3.16 to 8.40, 2 trials, 339 participants), at moderate quality. Where 3% improved on placebo, 12% to 77% would improve on the pill. Breast pain and other minor adverse events were more common on the pill. The levonorgestrel IUD lowered blood loss more than the pill (OR 0.21, 95% CI 0.09 to 0.48, 2 trials, 151 participants, low quality). The pill and the vaginal ring did not clearly differ, and evidence against NSAIDs was insufficient [25].
Population
805 women with heavy periods and regular cycles in 8 trials [25].
Sources
[25]
Caveats
Apart from the two placebo trials, the evidence was low to very low quality, mainly from lack of blinding and imprecision. The review covered heavy bleeding with no other gynecological or systemic disease behind it, so it does not test bleeding from fibroids [25].
LimitedStudied in women

Heavy bleeding with fibroids (hormonal IUD and combined pill)

Limited evidence: in women with fibroids, the hormonal IUD lowered bleeding and raised hemoglobin more than the combined pill in one small trial, without clearly shrinking fibroids.

Compared with a low-dose combined pill and oral norethisterone acetate [27]; the levonorgestrel IUD and placebo [28]; comparisons in 11 studies the source abstract does not describe [29]

The numbers and sources
Effect
In one trial of 44 women with fibroids, the levonorgestrel IUD reduced bleeding on the alkaline hematin test by 77.50% more than a low-dose combined pill (95% CI 70.44 to 84.56) and raised hemoglobin by 1.50 g/dL more (95% CI 0.85 to 2.15) at 12 months. Fibroid size did not clearly differ (MD 1.90%, 95% CI -12.24 to 16.04). Against oral norethisterone acetate, the IUD improved a visual bleeding score and raised hemoglobin by 10.14% more at 6 months, and spotting was more common (64.3% against 30%) [27]. A review of 2 trials found the combined pill did less than the levonorgestrel IUD for bleeding, quality of life and hemoglobin, and in a single trial at high risk of bias it shrank fibroids more than placebo [28]. A review of 11 studies of 10 to 104 women each found the levonorgestrel IUD reduced menstrual blood loss and raised hemoglobin, ferritin and hematocrit, with no evidence that fibroids shrank. Expulsion was uncommon and linked to fibroids larger than 3 cm [29].
Population
221 premenopausal women with fibroids in 4 trials [27]; women with fibroids and heavy bleeding in 2 trials [28]; premenopausal women with symptomatic fibroids in 11 studies [29].
Sources
[27], [28], [29]
Caveats
The Cochrane reviewers rated all of this evidence very low quality and wrote that they were uncertain of the effects [27]. The combined pill findings rest on single trials [28]. The 11-study review abstract does not describe the studies' designs [29].
ModerateStudied in women

Ovarian cancer

Linked to lower ovarian cancer risk in women, 15% to 29% lower for every 5 years of pill use, with protection lasting over 30 years after stopping.

Compared with women who never used the pill [8]

The numbers and sources
Effect
Risk fell more with longer use, by 29% per 5 years of use that had stopped under 10 years before, 19% for 10 to 19 years and 15% for 20 to 29 years. Ten years of use was estimated to lower ovarian cancer before age 75 from 1.2 to 0.8 per 100 users [8].
Population
23,257 women with ovarian cancer and 87,303 controls in 45 studies [8].
Sources
[8]
Caveats
Observational. Most use was of older, higher-dose pills, though the reduction was similar across decades [8].
ModerateStudied in women

Endometrial cancer

Linked to lower endometrial cancer risk in women, about 24% lower for every 5 years of pill use, lasting over 30 years after stopping.

Compared with women who never used the pill [9]

The numbers and sources
Effect
Each 5 years of use carried a risk ratio of 0.76 (95% CI 0.73 to 0.78). Ten years of use was estimated to lower endometrial cancer before age 75 from 2.3 to 1.3 per 100 women in high-income countries [9].
Population
27,276 women with endometrial cancer and 115,743 controls in 36 studies [9].
Sources
[9]
Caveats
Observational, with the strongest effect for carcinomas [9].
ModerateStudied in women

Fertility after stopping

Shown that 83% of women became pregnant within 12 months of stopping contraception, with no difference between hormonal methods and IUDs or by length of pill use.

Compared with other contraceptive methods, including IUDs [10]

The numbers and sources
Effect
The pooled pregnancy rate within 12 months of stopping was 83.1% (95% CI 78.2 to 88). It did not differ significantly between hormonal methods and IUDs, and neither progestin type nor length of pill use changed it [10]. Pregnancies occurred as early as 7 to 14 days after implant removal [11].
Population
14,884 women in 22 studies [10]; implant trial participants [11].
Sources
[10], [11]
Caveats
Studies varied, and the review included the contraceptive injection, which is not covered on this page.
StrongStudied in women

PMS and PMDD

Shown to ease overall premenstrual symptoms more than placebo, mostly in women with PMDD on a drospirenone pill. Depressive symptoms alone did not clearly differ.

Compared with placebo or another combined pill [30][31]

The numbers and sources
Effect
In two placebo-controlled trials in women with PMDD, a pill with drospirenone 3 mg and ethinyl estradiol 20 µg lowered premenstrual symptom scores after 3 months (MD -7.92, 95% CI -11.16 to -4.67) and eased impairment of productivity, social activities and relationships. Nausea (OR 3.15), bleeding between periods (OR 4.92) and breast pain (OR 2.67) were more common. In a 2-year trial, symptoms on a drospirenone pill matched a desogestrel pill [30]. Across 9 trials (1,205 women), combined pills improved overall premenstrual symptoms more than placebo (SMD 0.41, 95% credible interval 0.17 to 0.67) but not depressive symptoms (SMD 0.22, -0.06 to 0.47), and no pill did better than another [31].
Population
1,920 women in 5 trials [30]; 1,205 women with PMS or PMDD in 9 trials, mean ages 24.6 to 36.5 [31].
Sources
[30], [31]
Caveats
The placebo response was large, and the trials lasted 3 cycles, so longer effects are unknown [30]. Evidence for women with milder symptoms is thin [30].
ModerateStudied in women

Endometriosis pain (combined pill)

Shown to ease endometriosis period pain more than placebo in two small trials, in very low-quality evidence. Pain at 6 months matched goserelin in one trial.

Compared with placebo [32][33]; goserelin [32]; oral progestins and GnRH agonists [33]

The numbers and sources
Effect
Against placebo, combined pills lowered period pain on a visual analogue scale (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women) and on a 0 to 3 verbal scale (MD -1.30, 95% CI -1.84 to -0.76, 1 RCT, 96 women). At 6 months, pain did not differ from goserelin (MD -0.10 on a 1 to 10 scale, 95% CI -1.28 to 1.08, 50 women) [32]. A review of 9 RCTs and 9 observational studies found combined hormonal contraceptives lowered period pain, pelvic pain and pain with sex from baseline in most studies, about as much as or less than oral progestins and GnRH agonists [33].
Population
612 women with surgically confirmed endometriosis in 5 trials, 404 analyzed [32]; women with endometriosis in 18 studies [33].
Sources
[32], [33]
Caveats
Both placebo trials were at high risk of bias, with substantial involvement of the drug company that funded them [32]. Only 2 of the 9 trials in [33] were placebo-controlled, and most were not blinded.
LimitedStudied in women

Endometriosis pain after surgery (hormonal IUD)

Small trials found period pain fell more at 12 months with a hormonal IUD placed after endometriosis surgery than with no further treatment, at low certainty.

Compared with expectant management after surgery [34]

The numbers and sources
Effect
In one trial, the median fall in period pain on a visual analogue scale was 81 with the levonorgestrel IUD against 50 with no further treatment (P = 0.006, 55 women). In another, pain fell 50 points against 30 (P = 0.021, 40 women). The trials could not be pooled. Satisfaction was higher with the IUD, 75% against 50% in one trial [34].
Population
157 women having surgery for endometriosis in 4 RCTs [34].
Sources
[34]
Caveats
Certainty was low to very low, from risk of bias and imprecision. No trial reported overall pain [34].
LimitedStudied in women

Irregular cycles in PCOS

Limited evidence: one review found cycles became regular on the pill in women with PCOS, against none without medical treatment, at low certainty.

Compared with no medical treatment, placebo or lifestyle change [35]

The numbers and sources
Effect
Cycle regularity improved in 100% on the combined pill and 0% without medical treatment, at low certainty. Hirsutism and BMI did not differ from placebo or lifestyle change, weight was 8.0 kg lower than with no treatment, and quality of life was slightly higher, all at very low certainty [35].
Population
Women with PCOS in 4 RCTs, none of which could be pooled [35].
Sources
[35]
Caveats
Only 4 small trials. The review was written for the 2023 international PCOS guideline, whose authors note that pill use in PCOS rests mostly on evidence from the general population [35].

Mixed results2

ModerateStudied in women

Developing fibroids

Mixed results: current pill use was linked to less than half the fibroid risk of never use, while ever use was not significantly linked, in pooled observational studies.

Compared with women who never used the pill [26]

The numbers and sources
Effect
Against never use, ever use of the pill was not significantly linked to fibroids (RR 0.88, 95% CI 0.75 to 1.04), nor was former use (RR 0.96, 95% CI 0.84 to 1.08). Current use was linked to lower risk (RR 0.43, 95% CI 0.25 to 0.73), and 5 or more years of use to 17% lower risk [26].
Population
8,990 women with fibroids among 131,055 participants in 11 cohort and case-control studies [26].
Sources
[26]
Caveats
Observational, with heterogeneity of 64% to 92% [26]. Whether a woman is prescribed the pill can depend on symptoms that fibroids cause, so confounding and reverse causation are possible.
ModerateStudied in women

Excess hair and androgens in PCOS

Mixed results: against metformin, hair growth improved about the same in one review and more on the pill in overweight women in another.

Compared with metformin [36][37]; metformin combined with the pill [36][37]; placebo or lifestyle change [35]; other combined pills [38]

The numbers and sources
Effect
Against metformin, hirsutism did not differ, while free androgen index was 7.08 lower, SHBG 118.61 nmol/L higher and testosterone 0.48 nmol/L lower on the pill. Adding metformin to the pill lowered free androgen index and raised SHBG further [36]. A Cochrane review found metformin may improve hirsutism less than the pill in women with BMI 25 to 30 (MD 1.92, 95% CI 1.21 to 2.64), with an uncertain difference at other BMIs, and the pill plus metformin improved hirsutism more than the pill alone [37]. Hirsutism did not differ from placebo or lifestyle change, at very low certainty [35]. Pills with cyproterone acetate lowered hirsutism and testosterone (MD 0.38 nmol/L) more than conventional pills, and high and low estrogen doses did not differ [38].
Population
36 RCTs in women with PCOS [36]; 44 RCTs with 2,253 women and adolescents with PCOS [37]; 4 RCTs [35]; 19 RCTs comparing two pills [38].
Sources
[36], [37], [35], [38]
Caveats
Cochrane evidence quality was very low to low [37]. The guideline reviewers noted the higher clot risk of cyproterone acetate pills in the general population [38].

Doses studied

Yaz contains drospirenone 3 mg with ethinyl estradiol 0.02 mg [2]. The Nexplanon implant contains 68 mg etonogestrel and lasts up to 5 years [11], and the Mirena IUD releases levonorgestrel [3]. Opill contains norgestrel 0.075 mg [12]. The Danish cohorts grouped combined pills by ethinyl estradiol dose, 20 µg or 30 to 40 µg, and by progestin, listed under Risks.

Risks

Reported risks11

ModerateStudied in womenVery common

Irregular bleeding, headache and nausea

Shown to raise irregular bleeding, headache and nausea on combined pills, irregular bleeding in 39% to 60% against 18% on placebo. Bleeding changes led most implant stops.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Against placebo, combined pills raised irregular bleeding (RR 2.63), from 18% to between 39% and 60%, headache (RR 1.51), nausea (RR 1.64) and any adverse event (RR 1.31) [5]. In implant trials, bleeding pattern changes were the most common reason for stopping (11.1%), and bleeding ranged from none in about 1 in 5 women to frequent or prolonged [11].
Population
Women in dysmenorrhea trials [5]; etonogestrel implant trials [11].
Sources
[5], [11]
Caveats
Heterogeneity was moderate for some outcomes [5].
ModerateUncommon

Hormonal IUD: perforation, expulsion and ectopic pregnancy

The label reports uterine perforation in under 0.1% in trials, and about half of the rare pregnancies with Mirena in place are ectopic.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
Perforation occurred in under 0.1% in trials, which excluded breastfeeding women. In a cohort of 326,658 insertions, perforation was 1.32 per 1,000 insertions with no recent delivery and up to 11.78 per 1,000 between 4 days and 6 weeks after birth. Expulsion may go unnoticed. Ectopic pregnancy occurred at about 0.1% per year in trials, and about half of pregnancies with Mirena in place are likely ectopic [3].
Population
Mirena trial participants and a US cohort of 326,658 insertions [3].
Sources
[3]
Caveats
Rates depend on timing after childbirth and breastfeeding [3].
StrongStudied in womenRare

Blood clots in the veins with combined pills

Shown to raise venous clots about 3.5 times, more with desogestrel, gestodene or drospirenone than levonorgestrel, at 3 to 9 per 10,000 women a year.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
Combined pill use raised venous thrombosis risk against non-use (RR 3.5, 95% CI 2.9 to 4.3). Pills with 30 to 35 µg ethinyl estradiol and gestodene, desogestrel, cyproterone acetate or drospirenone carried 50% to 80% higher risk than levonorgestrel pills, and higher estrogen doses raised risk [14]. In Danish women, relative risks against non-users were 2.9 for levonorgestrel pills, 6.6 for desogestrel, 6.2 for gestodene and 6.4 for drospirenone, and progestin-only pills and hormonal IUDs did not raise it [15]. The label estimates 3 to 9 per 10,000 woman-years on combined pills against 1 to 5 in non-pregnant non-users, highest in the first year and lower than in pregnancy and after birth [2].
Population
26 studies [14]; Danish women aged 15 to 49 over 8,010,290 woman-years [15]; label statement [2].
Sources
[14], [15], [2]
Caveats
Observational studies. Non-users in two cohorts had 0.19 and 0.37 clots per 1,000 person-years [14].
LimitedStudied in womenRare

Blood clots with the patch, ring, implant and hormonal IUD

Linked to venous clots 7.9 times higher on the patch and 6.5 times on the ring than non-use, 8 to 10 per 10,000 years, not on the hormonal IUD.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
Against non-users, confirmed venous thrombosis was raised on the patch (RR 7.9, 95% CI 3.5 to 17.7) and ring (RR 6.5, 95% CI 4.7 to 8.9), at 9.7 and 7.8 events per 10,000 exposure years, against 2.1 in non-users. It was 1.4 (95% CI 0.6 to 3.4) on the implant and 0.6 (95% CI 0.4 to 0.8) on the levonorgestrel IUD. Against levonorgestrel pills, the patch carried 2.3 times and the ring 1.9 times the risk [16]. The patch label warns of possibly greater clot risk at a BMI above 30 [13].
Population
1,626,158 Danish women aged 15 to 49, 9,429,128 woman-years [16].
Sources
[16], [13]
Caveats
One national cohort, observational.
LimitedStudied in womenRare

Stroke and heart attack

Linked to 1.3 to 2.3 times the risk of clot-related stroke and heart attack on pills with 30 to 40 µg ethinyl estradiol, with low absolute rates.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
Overall, thrombotic stroke occurred at 21.4 and heart attack at 10.1 per 100,000 person-years. With 30 to 40 µg ethinyl estradiol, relative risks ranged from 1.5 to 2.2 for stroke and 1.3 to 2.3 for heart attack by progestin. With 20 µg they were 0.9 to 1.7. The vaginal ring carried 2.5 for stroke [17].
Population
1,626,158 Danish women aged 15 to 49, 14,251,063 person-years [17].
Sources
[17]
Caveats
Observational, one cohort.
ModerateStudied in womenRare

Breast cancer

Linked to about 20% higher breast cancer risk in current and recent users, 1 extra case per 7,690 women a year, similar for progestin-only methods including the hormonal IUD.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
Current or recent hormonal contraception raised breast cancer risk against never use (RR 1.20, 95% CI 1.14 to 1.26), from 1.09 with under 1 year to 1.38 with over 10 years. The levonorgestrel IUD carried 1.21. The absolute increase was 13 per 100,000 person-years [18]. In a UK study and meta-analysis, risks were similar for combined pills (OR 1.23), progestin-only pills (RR 1.29), implants (RR 1.28) and IUDs (RR 1.21), with a 15-year excess of 8 per 100,000 users aged 16 to 20 and 265 per 100,000 aged 35 to 39 [19].
Population
1.8 million Danish women followed 10.9 years on average [18]; 9,498 cases and 18,171 controls, plus 12 earlier studies [19].
Sources
[18], [19]
Caveats
Observational. Risk stayed raised after 5 or more years of use [18].
ModerateStudied in womenHow often is not known

Lower testosterone and higher SHBG

Shown to lower total testosterone and cut free testosterone by about 61% in healthy women on combined pills, while SHBG rose about 99 nmol/L.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Total testosterone fell (MD -0.49 nmol/L, 95% CI -0.55 to -0.42), free testosterone fell 61% (relative level 0.39), and SHBG rose (MD 99.08 nmol/L, 95% CI 86.43 to 111.73). Ethinyl estradiol dose and progestin type did not change the testosterone fall, but pills with second-generation progestins or 20 to 25 µg ethinyl estradiol raised SHBG less [7].
Population
1,495 healthy women aged 18 to 40 in 42 studies [7].
Sources
[7]
Caveats
Half the studies were non-comparative. The clinical effects of lower androgens remain unclear [7].
LimitedHow often is not known

FDA boxed warning: smoking and serious cardiovascular events

FDA states smoking raises the risk of serious cardiovascular events with combined hormonal birth control, more with age and over 35.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The combined pill label states that cigarette smoking increases the risk of serious cardiovascular events, rising with age, particularly over 35, and with the number of cigarettes, and that women over 35 who smoke are not to use it [2]. The patch label carries the same warning and contraindicates it at a BMI of 30 or higher because of possibly greater clot risk, and says it may prevent pregnancy less well at 90 kg or more [13].
Population
Label statements [2][13].
Sources
[2], [13]
Caveats
The boxed warning gives no rate.
LimitedHow often is not known

Implant insertion and removal problems

FDA states improper implant insertion raises the risk of complications, including nerve injury, scarring and migration into blood vessels, so Nexplanon is available only through a restricted program.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states improper insertion increases the risk of complications. Reported complications include pain, numbness, bleeding, hematoma, scarring, infection and migration into blood vessels, including lung vessels, sometimes needing surgery. An implant not inserted may go unnoticed and lead to pregnancy [11].
Population
Label statements [11].
Sources
[11]
Caveats
No rate given.
LimitedHow often is not known

High potassium with drospirenone

The label warns drospirenone can raise potassium, comparable to spironolactone 25 mg, and contraindicates it in kidney, liver or adrenal conditions that raise potassium.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Drospirenone 3 mg has anti-mineralocorticoid activity comparable to spironolactone 25 mg, with potential for high potassium in high-risk patients. The label advises checking potassium in the first cycle for women on other long-term drugs that raise potassium [2].
Population
Label statement [2].
Sources
[2]
Caveats
No rate given.
ModerateHow often is not known

Drugs that weaken the pill

The label warns enzyme-inducing drugs such as rifampin, carbamazepine and St. John's wort may weaken combined pills, while common antibiotics showed no effect on pregnancy rates or hormone levels.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Drugs or herbal products that induce CYP3A4, including phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampin, topiramate and St. John's wort, may decrease effectiveness or cause breakthrough bleeding [2]. For non-rifamycin antibiotics, two studies found no difference in pregnancy rates, and no study found changes in ovulation suppression or progestin levels [24].
Population
Label statement [2]; 29 studies [24].
Sources
[2], [24]
Caveats
Data were limited for some antibiotic classes [24].

Mixed results1

ModerateStudied in womenHow often is not known

Depression

Mixed results: a national cohort linked hormonal birth control to more antidepressant use, highest in teens, while randomized trials found no worsening of depressive symptoms in adult women.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against non-users, first antidepressant use was higher on combined pills (RR 1.23), progestin-only pills (RR 1.34), the patch (RR 2.0), the ring (RR 1.6) and the levonorgestrel IUD (RR 1.4), and higher in adolescents on combined pills (RR 1.8) [20]. A network meta-analysis of randomized trials found no worsening of depressive symptoms against placebo (median SMD -0.04) [21].
Population
1,061,997 Danish women aged 15 to 34 followed 6.4 years [20]; 5,833 women in 12 trials [21].
Sources
[20], [21]
Caveats
The cohort is observational [20]. The trials rarely enrolled first-time or adolescent users [21].

Checked, no increase found1

StrongStudied in women

Weight gain

Not shown to cause meaningful weight gain in women on combined methods in placebo-controlled trials. Progestin-only methods other than the injection showed limited change, usually under 2 kg.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Four trials with a placebo or no-intervention group found no evidence that combined pills or the patch cause weight change, and stopping for weight did not differ between groups [22]. Across 22 studies of progestin-only methods, groups mostly did not differ in weight, and mean gain at 6 or 12 months was under 2 kg in most studies. Greater gains were seen with the injection [23].
Population
49 trials of combined methods [22]; 11,450 women in 22 studies [23].
Sources
[22], [23]
Caveats
Low-quality evidence for progestin-only methods [23]. The injection is not covered on this page.

Claims tested and not found

  1. That birth control causes weight gain. Placebo-controlled trials of combined pills and the patch found no causal link to weight change [22], and progestin-only methods other than the injection showed little difference [23].
  2. That hormonal birth control harms later fertility. 83.1% of women conceived within 12 months of stopping, with no difference by method or length of pill use [10].
  3. That common antibiotics make the pill fail. Pregnancy rates, ovulation and progestin levels did not change with non-rifamycin antibiotics [24].

Related

Menopausal hormone therapy

Sources

  1. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. New England Journal of Medicine. 2012. https://doi.org/10.1056/NEJMoa1110855
  2. U.S. Food and Drug Administration. YAZ (drospirenone and ethinyl estradiol) tablets, prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=065f33e4-b587-4e66-b896-ca9ab7b7c876
  3. U.S. Food and Drug Administration. MIRENA (levonorgestrel-releasing intrauterine system), prescribing information. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dcbd6aa2-b3fa-479a-a676-56ea742962fc
  4. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.CD004425.pub6
  5. Schroll JB, Black AY, Farquhar C, Chen I. Combined oral contraceptive pill for primary dysmenorrhoea. Cochrane Database of Systematic Reviews. 2023. https://doi.org/10.1002/14651858.CD002120.pub4
  6. Bofill Rodriguez M, Lethaby A, Jordan V. Progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database of Systematic Reviews. 2020. https://doi.org/10.1002/14651858.CD002126.pub4
  7. Zimmerman Y, Eijkemans MJC, Coelingh Bennink HJT, et al. The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis. Human Reproduction Update. 2014. https://doi.org/10.1093/humupd/dmt038
  8. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. The Lancet. 2008. https://doi.org/10.1016/S0140-6736(08)60167-1
  9. Collaborative Group on Epidemiological Studies on Endometrial Cancer. Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. The Lancet Oncology. 2015. https://doi.org/10.1016/S1470-2045(15)00212-0
  10. Girum T, Wasie A. Return of fertility after discontinuation of contraception: a systematic review and meta-analysis. Contraception and Reproductive Medicine. 2018. https://doi.org/10.1186/s40834-018-0064-y
  11. U.S. Food and Drug Administration. NEXPLANON (etonogestrel implant), prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487f8a62-e142-457c-97cc-2e398fde7594
  12. U.S. Food and Drug Administration. OPILL (norgestrel) tablets 0.075 mg, Drug Facts label. 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=69dfa2ac-6a7e-4587-929c-9acabd97973b
  13. U.S. Food and Drug Administration. XULANE (norelgestromin and ethinyl estradiol transdermal system), prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7848550-086a-43d8-8ae5-047f4b9e4382
  14. de Bastos M, Stegeman BH, Rosendaal FR, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.CD010813.pub2
  15. Lidegaard O, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ. 2011. https://doi.org/10.1136/bmj.d6423
  16. Lidegaard O, Nielsen LH, Skovlund CW, Løkkegaard E. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ. 2012. https://doi.org/10.1136/bmj.e2990
  17. Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and myocardial infarction with hormonal contraception. New England Journal of Medicine. 2012. https://doi.org/10.1056/NEJMoa1111840
  18. Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary Hormonal Contraception and the Risk of Breast Cancer. New England Journal of Medicine. 2017. https://doi.org/10.1056/NEJMoa1700732
  19. Fitzpatrick D, Pirie K, Reeves G, Green J, Beral V. Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis. PLOS Medicine. 2023. https://doi.org/10.1371/journal.pmed.1004188
  20. Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016. https://doi.org/10.1001/jamapsychiatry.2016.2387
  21. de Wit AE, de Vries YA, de Boer MK, et al. Hormonal contraceptive use and depressive symptoms: systematic review and network meta-analysis of randomised trials. BJPsych Open. 2021. https://doi.org/10.1192/bjo.2021.64
  22. Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.CD003987.pub5
  23. Lopez LM, Ramesh S, Chen M, et al. Progestin-only contraceptives: effects on weight. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD008815.pub4
  24. Simmons KB, Haddad LB, Nanda K, Curtis KM. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. American Journal of Obstetrics and Gynecology. 2018. https://doi.org/10.1016/j.ajog.2017.07.003
  25. Lethaby A, Wise MR, Weterings MA, et al. Combined hormonal contraceptives for heavy menstrual bleeding. Cochrane Database of Systematic Reviews. 2019. https://doi.org/10.1002/14651858.cd000154.pub3
  26. Qin J, Yang T, Kong F, Zhou Q. Oral contraceptive use and uterine leiomyoma risk: a meta-analysis based on cohort and case-control studies. Archives of Gynecology and Obstetrics. 2013. https://doi.org/10.1007/s00404-013-2797-9
  27. Sangkomkamhang US, Lumbiganon P, Pattanittum P. Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy). Cochrane Database of Systematic Reviews. 2020. https://doi.org/10.1002/14651858.cd008994.pub3
  28. Moroni RM, Martins WP, Dias SV, et al. Combined oral contraceptive for treatment of women with uterine fibroids and abnormal uterine bleeding: a systematic review. Gynecologic and Obstetric Investigation. 2015. https://doi.org/10.1159/000369390
  29. Jiang W, Shen Q, Chen M, et al. Levonorgestrel-releasing intrauterine system use in premenopausal women with symptomatic uterine leiomyoma: a systematic review. Steroids. 2014. https://doi.org/10.1016/j.steroids.2014.05.002
  30. Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database of Systematic Reviews. 2012. https://doi.org/10.1002/14651858.cd006586.pub4
  31. de Wit AE, de Vries YA, de Boer MK, et al. Efficacy of combined oral contraceptives for depressive symptoms and overall symptomatology in premenstrual syndrome: pairwise and network meta-analysis of randomized trials. American Journal of Obstetrics and Gynecology. 2021. https://doi.org/10.1016/j.ajog.2021.06.090
  32. Brown J, Crawford TJ, Datta S, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.cd001019.pub3
  33. Jensen JT, Schlaff W, Gordon K. Use of combined hormonal contraceptives for the treatment of endometriosis-related pain: a systematic review of the evidence. Fertility and Sterility. 2018. https://doi.org/10.1016/j.fertnstert.2018.03.012
  34. Gibbons T, Georgiou EX, Cheong YC, Wise MR. Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery. Cochrane Database of Systematic Reviews. 2021. https://doi.org/10.1002/14651858.cd005072.pub4
  35. Forslund M, Melin J, Alesi S, et al. Combined oral contraceptive pill compared with no medical treatment in the management of polycystic ovary syndrome: A systematic review. Clinical Endocrinology. 2023. https://doi.org/10.1111/cen.14913
  36. Melin J, Forslund M, Alesi S, et al. Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis. The Journal of Clinical Endocrinology & Metabolism. 2024. https://doi.org/10.1210/clinem/dgad465
  37. Fraison E, Kostova E, Moran LJ, et al. Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome. Cochrane Database of Systematic Reviews. 2020. https://doi.org/10.1002/14651858.cd005552.pub3
  38. Forslund M, Melin J, Alesi S, et al. Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis. European Journal of Endocrinology. 2023. https://doi.org/10.1093/ejendo/lvad082

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