Abstract
Objective:
To evaluate the association of different contraceptive methods on the incidence and severity of acne.
Methods:
Using a de-identified commercial claims database, we performed a retrospective cohort study evaluating the incidence of clinical encounters for acne in the first year after initiation of contraception among female patients aged 12–40 years who were new contraceptive users. To evaluate the association of contraception class with acne severity, a subgroup analysis was performed among a cohort of patients with a history of acne examining the incidence of treatment escalation from topical acne medications to an oral tetracycline-class antibiotic in the year after initiation of contraception.
Results:
Among new contraceptive users with no history of acne (n=336,738), compared to combined oral contraceptives, the copper intrauterine device (HR 1.14; 95% CI 1.01–1.29) and levonorgestrel intrauterine devices (HR 1.09; 95% CI 1.03–1.16) were associated with increased risk of clinical encounters with for acne. Among those with a history of acne (n=21,178), compared to combined oral contraceptives, the copper intrauterine device (HR 1.44; 95% CI 1.00–2.06) and levonorgestrel intrauterine devices (HR 1.34; 95% CI 1.10–1.64) were associated with increased risk of treatment escalation from topical acne medications to an oral tetracycline class antibiotic.
Conclusion:
Combined oral contraceptives appear to be associated with a modest (or small) protective effect with respect to incident acne and treatment escalation compared to other contraceptive methods. However, absolute differences between contraceptive methods were small.
Precis
Combined oral contraceptive use is associated with a lower risk of acne compared to other contraceptive methods, although absolute differences between methods were small.
Introduction
Acne is one of the most common diseases worldwide, affecting 85% of adolescents.1 In addition, acne frequently persists into adulthood, with over 50% of women reporting acne in their 20s and 35% of women reporting acne in their 30s.2 The pathogenesis of acne is multifactorial, with production of androgens and sebogenic hormones playing an important role.3 Given that several forms of contraception can influence these hormonal signaling pathways, choice of contraception may influence the incidence and severity of acne in women.
Several placebo-controlled trials have demonstrated that combined oral contraceptives (COCs) are an effective treatment for acne and patients with acne are frequently prescribed COCs, with three COC products FDA approved for acne.4–9 Although there are multiple COC formulations and COCs containing progestins with antiandrogenic properties such as drospirenone may have greater effectiveness, a recent Cochrane review concluded that there were no important and consistent differences between COCs on acne.8,10–14
However, acne can also be a reason for contraceptive discontinuation and different contraception classes may have differing effects on acne.15–19 Two small randomized trials have found that acne may be more likely to be reported among users of progestin-only methods than COCs.20,21 In addition, a survey study of patient-reported effects of contraception on acne suggests that progestin-only methods, including depot medroxyprogesterone acetate (DMPA) injections, the etonogestrel subdermal implant, and levonorgestrel-releasing intrauterine devices (IUDs) worsened acne, while COCs improved acne.14
Much of the existing literature is limited by its focus on a comparison of only a few contraception classes and reliance on patient report for acne outcomes. In addition, since COCs are an effective treatment for acne, it is possible that some of the incident acne reported with other contraceptives could be due to the discontinuation of prior COCs rather than from the contraceptive method itself. There is also a lack of data on the effects of progesterone-only contraception and long-acting reversible contraception methods on acne. The purpose of this study was to evaluate the association of contraceptive method on the incidence and severity of acne among new contraception users and among women who switched contraceptive methods. Based on their mechanism of action, we hypothesized that combined oral contraceptives would have a beneficial effect, the copper IUD would have a neutral effect, and progesterone-only oral contraceptives, levonorgestrel IUDs, the etonogestrel implant, and DMPA injection would have a negative effect on acne
Methods
This study was a retrospective cohort study of female patients prescribed contraception in the Optum de-identified Clinformatics Data Mart Database, a de-identified commercial claims database for approximately 12–14 million individuals annually in the United States. These data include both medical and pharmacy claims, as well as patient demographic information such as age and gender. The patient population available in the database is similar to the demographics of the United States population with respect to gender, age, and geographic distribution.22
Study inclusion criteria were: (1) women aged 12–40 years; (2) at least one year of continuous enrollment prior to and after the index date, which was defined as the date of the first use of contraception; (3) at least one year of contraception use after the index date. Subjects were excluded if they had a history of pregnancy within one year prior to or one year after the index date.
For the primary analysis of the incidence of clinical encounters for acne in the year after initiation of contraception, additional exclusion criteria were (1) any pharmacy claim for an acne topical (i.e. benzoyl peroxide, topical retinoids, topical antibiotics) prior to the index date; (2) any encounters with an International Classification of Diseases (ICD) 9 or 10 code for acne (706.1, L70.0, L70.1, L70.8, L70.9) prior to the index date.
Contraception classes were defined as COCs, progestin-only oral contraceptives, DMPA injection, etonogestrel implant, levonorgestrel IUDs, and the non-hormonal copper IUD. COCs were identified by their National Drug Codes (NDC). Prescriptions were consolidated into courses of therapy, with prescriptions separated by fewer than 30 days considered to be part of a single course of therapy. DMPA injections were identified by their NDC and Current Procedural Terminology (CPT) codes and injections separated by fewer than 120 days (to allow for potential small gaps of up to 30 days between injections due to logistical issues) were considered part of a single course of therapy. Placement and removal IUDs and the etonogestrel implant were identified by their associated CPT and ICD codes. If the same type of IUD was replaced at the time of IUD removal, these IUDs were considered part of a single course of therapy.
Outcomes were evaluated during one year of follow-up after the index date. For our primary analysis of the incidence of clinical encounters for acne after starting contraception, the outcome was defined as the first encounter with an ICD code for acne after the index date.23
In addition, to evaluate the association of contraception class on acne severity, a subgroup analysis was performed among a cohort of patients with a history of clinical encounters for acne examining the incidence of treatment escalation from topical acne medications to an oral tetracycline-class antibiotic in the year after initiation of contraception. This outcome was chosen as tetracycline-class antibiotics are the most common systemic therapy prescribed for acne.9,24
To evaluate the association of discontinuing a COC on acne, a subgroup analysis was performed evaluating incident clinical encounters for acne among patients who had been using a COC for at least 90 days and then discontinued this COC and either started another form of contraception within 90 days of discontinuation (which could be a different COC) or did not receive any prescription for contraception for the next year. To reduce risk of loss to follow-up for those on no contraception, at least at least one clinical encounter of any type after the index date was required in this analysis.
Age, history of polycystic ovarian syndrome (PCOS), and calendar year in which the contraception was started were evaluated as factors that may influence the incidence of clinical encounters with an ICD code for acne and type of contraceptive prescribed. In addition, the total number of encounters (independent of those for acne) in the year prior to and the year after the index date were evaluated as factors that may influence the likelihood of having a clinical encounter with an ICD code for acne due to increased interaction with the healthcare system.
Multivariable Cox proportional hazard models, adjusting for each of the covariates above, were used to evaluate the association between contraception class and the development of each of the outcomes of interest.25 Results are presented as adjusted hazard ratios (HR), adjusted odds ratios (OR), and 95% confidence intervals (CI). The assumption of proportionality was confirmed using log-log plots.
To evaluate for the potential influence of unmeasured confounding in our primary analysis, a sensitivity analysis was performed using E-values.26 Since ICD-9 codes for acne have a sensitivity and positive predictive value of approximately 85%, there is the possibility that some patients with acne may not receive an ICD code for acne prior to the index date.23 If these patients with acne who did not receive an ICD code prior to index data are also more likely to receive one form of contraception (for example, COCs, since these are FDA-approved for acne) and more likely to receive an ICD code for acne after the index date, it could result in confounding by indication. The E-value represents the minimum strength of association that an unmeasured confounder would need to have with both the treatment and outcome to fully explain away a specific treatment–outcome association. To help contextualize the results, we also evaluated the odds of having a history of acne for each type of contraception, controlling for age, history of PCOS, and calendar year in which the contraception was started. Statistical analyses were performed in Stata 15 (StataCorp, College Station, Texas). This study was deemed exempt by Institutional Review Board of the University of Pennsylvania since it involved de-identified data. This study was conducted in adherence with the STROBE guidelines.27
Results
There were 336,738 subjects that met the study criteria for the primary analysis (Table 1). The most common contraceptives prescribed were COCs (82.9%). Other methods included levonorgestrel IUDs (10.6%), copper IUD (2.1%), etonogestrel implant (1.9%), progestin only oral contraceptive (1.3%), and DMPA injection (1.2%).
Table 1.
Subject Demographics, n=336,738
| Contraception Class | Combined OC | Progestin-only OC | Copper IUD | Levonorgestrel IUD | Etonogestrel Implant | DMPA Injection |
|---|---|---|---|---|---|---|
| n (%) | 279144 (82.9) | 4433 (1.3) | 7203 (2.1) | 35597 (10.6) | 6330 (1.9) | 4031 (1.2) |
| Age, years, mean (SD) | 26.5 (7.4) | 31.5 (6.1) | 31.5 (5.6) | 31.8 (5.8) | 23.3 (6.7) | 26.1 (8.1) |
| <20, years-old, n (%) | 64405 (23.1) | 239 (5.4) | 200 (2.8) | 1168 (3.3) | 2318 (36.6) | 1255 (31.1) |
| 20–24, years-old, n (%) | 56727 (20.3) | 377 (8.5) | 729 (10.1) | 3457 (9.7) | 1764 (27.9) | 616 (15.3) |
| 25–29, years-old, n (%) | 56848 (20.4) | 831 (18.8) | 1553 (21.6) | 6930 (19.5) | 1033 (16.3) | 629 (15.6) |
| 30–34, years-old, n (%) | 47697 (17.1) | 1309 (29.5) | 2244 (31.2) | 10187 (28.6) | 645 (10.2) | 697 (17.3) |
| 35–40, years-old, n (%) | 53467 (19.2) | 1677 (37.8) | 2477 (34.4) | 13855 (38.9) | 570 (9.0) | 834 (20.7) |
| Contraceptive Course Duration, mean (SD) | 797 (489) | 663 (418) | 866 (265) | 858 (268) | 777 (311) | 668 (362) |
| History of PCOS, n (%) | 4132 (1.5) | 95 (2.1) | 117 (1.6) | 684 (1.9) | 84 (1.3) | 26 (0.6) |
| Incident Acne in Year After Index Date, n (%) | 10979 (3.9) | 137 (3.1) | 260 (3.6) | 1240 (3.5) | 228 (3.6) | 126 (3.1) |
| Age <20, years-old, n (%) | 3331 (5.2) | 20 (8.4) | 10 (5.5) | 50 (4.4) | 102 (4.4) | 55 (4.5) |
| Age 20–29, years-old, n (%) | 4801 (4.2) | 45 (3.8) | 96 (4.3) | 432 (4.2) | 102 (3.6) | 36 (2.9) |
| Age 30–40, years-old, n (%) | 2847 (2.8) | 72 (2.5) | 154 (3.3) | 758 (3.2) | 24 (1.9) | 35 (2.3) |
OC: oral contraceptive; IUD: intrauterine device; DMPA: depot medroxyprogesterone acetate
Incident acne was recorded among 2–8% of women in the study, with higher rates among younger women, as shown in Table 1. Compared to COCs, the copper IUD (adjusted HR 1.14; 95% CI 1.01–1.29) and levonorgestrel IUDs (adjusted HR 1.09; 95% CI 1.03–1.16) were associated with increased risk of clinical encounters with an ICD code for acne in the first year after the index date. The etonogestrel implant (adjusted HR 0.83; 95% CI 0.72–0.94) and the DMPA injection (adjusted HR 0.70; 95% CI 0.59–0.84) were associated with decreased risk of incident clinical encounters for acne (Table 2). The unadjusted absolute difference in the proportion of women with acne between contraception classes was <1% (Table 1). The results were similar in a sensitivity analysis excluding all women with a history of PCOS (data not shown).
Table 2.
Influence of contraception class on the development of incident clinical acne and on treatment escalation among those on topical medications for acne
| Incident Acne n=336,738 | Treatment Escalation n=21,178 | |||
|---|---|---|---|---|
| HR (95% CI), crude | HR (95% CI), adj | HR (95% CI), crude | HR (95% CI), adj | |
| Contraception Class | ||||
| Combined oral contraceptive | [Reference] | [Reference] | ||
| Progestin-only oral contraceptive | 0.78 (0.66 to 0.92) | 1.14 (0.96 to 1.35) | 1.03 (0.61 to 1.74) | 1.28 (0.75 to 2.17) |
| Copper Intrauterine Device | 0.91 (0.81 to 1.03) | 1.14 (1.01 to 1.29) | 1.22 (0.86 to 1.74) | 1.44 (1.00 to 2.06) |
| Levonorgestrel Intrauterine Device | 0.88 (0.83 to 0.93) | 1.09 (1.03 to 1.16) | 1.14 (0.96 to 1.37) | 1.34 (1.10 to 1.64) |
| Etonogestrel Implant | 0.91 (0.80 to 1.04) | 0.83 (0.72 to 0.94) | 0.62 (0.39 to 0.98) | 0.66 (0.41 to 1.05) |
| DMPA Injection | 0.79 (0.66 to 0.94) | 0.70 (0.59 to 0.84) | 0.87 (0.50 to 1.54) | 0.85 (0.48 to 1.51) |
| History of polycystic ovarian syndrome | 1.01 (0.88 to 1.16) | 0.96 (0.69 to 1.32) | ||
| Calendar year contraception was started | 1.03 (1.03 to 1.04) | 0.99 (0.97 to 1.01) | ||
| Non-acne visits prior to index date, sqrt | 0.88 (0.87 to 0.89) | 0.98 (0.95 to 1.02) | ||
| Non-acne visits after index date, sqrt | 1.24 (1.23 to 1.26) | 1.09 (1.05 to 1.13) | ||
| Age | ||||
| <20 years-old | [Reference] | [Reference] | ||
| 20–24 years-old | 0.82 (0.78 to 0.87) | 0.83 (0.74 to 0.94) | ||
| 25–29 years-old | 0.82 (0.78 to 0.86) | 1.06 (0.92 to 1.23) | ||
| 30–34 years-old | 0.62 (0.59 to 0.66) | 0.76 (0.63 to 0.92) | ||
| 35–40 years-old | 0.47 (0.44 to 0.50) | 0.67 (0.55 to 0.83) | ||
HR: hazard ratio; CI: confidence interval; DMPA: depot medroxyprogesterone acetate; adj: adjusted
In the analysis to evaluate for the potential influence of unmeasured confounding of contraceptive method on incident acne, the E-Value point estimates ranged from 1.40–2.21 (Table 3). These signify the strength an unmeasured confounder would need to have with both the treatment and outcome to fully explain away the results. For example, the E-Value estimate for the DMPA injection was 2.21, with a lower 1.67 E-Value estimate for the 95% CI. If there were an unmeasured confounder that is associated with both being prescribed a DMPA injection and the development of incident acne with a strength of association of >1.67, the confidence interval could be moved to include the null, and we could no longer conclude that DMPA injection is associated with a lower risk of incident acne than COCs among new contraceptive users. The E-value for the implant and incident acne shows similar results, with possible confounding.
Table 3.
Sensitivity analysis and E-values
| E-value (For Table 2, Incident Acne Results) | Odds of acne if prescribed n=1,174,436 | ||
|---|---|---|---|
| Point estimate | 95% CI | OR (95% CI), adj | |
| Contraception Class | |||
| Combined oral contraceptive | [Reference] | [Reference] | [Reference] |
| Progestin-only oral contraceptive | 1.57 | 1.00 | 0.66 (0.64–0.68) |
| Copper Intrauterine Device | 1.54 | 1.11 | 0.91 (0.86–0.96) |
| Levonorgestrel Intrauterine Device | 1.40 | 1.23 | 0.80 (0.77–0.82) |
| Etonogestrel Implant | 1.70 | 1.32 | 0.52 (0.49–0.55) |
| DMPA Injection | 2.21 | 1.67 | 0.53 (0.51–0.56) |
OR: odds ratio; CI: confidence interval; DMPA: depot medroxyprogesterone acetate; adj: adjusted
The E-value represents the minimum strength of association that an unmeasured confounder would need to have with both the treatment and outcome to fully explain away a specific treatment–outcome association. For example, the DMPA injection E-value for the 95% CI of 1.67 indicates the CI could be moved to include the null by an unmeasured confounder that is associated with both DMPA injection and incident acne by an OR of at least 1.67. Of note, the odds of being prescribed DMPA injection compared to a combined oral contraceptive is 0.53 among those with a history of acne. Taking the inverse of 0.53 (1/0.53=1.89) because it is a negative rather than positive association, we see that 1.89 is greater than 1.67, the E-value for the 95% CI, so it is possible that acne which is not coded could be an unmeasured confounder that could explain away the observed association between DMPA and decreased risk of incident acne. Similarly, the inverse of the OR of being prescribed an implant among those with acne (1/0.52=1.92) is greater than the E-value for the 95% CI 1.32 (as well as the point estimate 1.70).
Compared to COCs, the copper IUD (adjusted HR 1.44; 95% CI 1.00–2.06) and levonorgestrel IUDs (adjusted HR 1.34; 95% CI 1.10–1.64) were associated with increased risk of treatment escalation from topical acne medications to an oral tetracycline class antibiotic in the first year after the index date (Table 2, n=21,178). None of the other comparisons were statistically significant.
Among those who switched from a COC to another form of contraception, compared to COCs, progestin-only oral contraceptives (adjusted HR 1.70; 1.23–2.35), levonorgestrel IUDs (adjusted HR 1.93; 95% CI 1.69–2.22), the etonogestrel implant (adjusted HR 1.45; 95% CI 1.08–1.95), and the copper IUD (adjusted HR 1.70; 95% CI 1.23–2.35) were each associated with increased risk of clinical encounters for acne (Table 4, n=113,708). Switching to DMPA injections or no contraception were not associated with statistically significant differences in the risk of incident clinical encounters for acne.
Table 4.
Influence of switching to a different contraception class on the development of incident clinical acne and treatment escalation (n=113,708)
| Incident Acne | ||
|---|---|---|
| HR (95% CI), crude | HR (95% CI), adj | |
| Contraception Class | ||
| Combined oral contraceptive | [Reference] | |
| Progesterone only oral contraceptive | 1.64 (1.19 to 2.27) | 1.70 (1.23 to 2.35) |
| Copper Intrauterine Device | 1.80 (1.35 to 2.42) | 1.76 (1.31 to 2.36) |
| Levonorgestrel Intrauterine Device | 1.95 (1.70 to 2.23) | 1.93 (1.69 to 2.22) |
| Etonogestrel Implant | 1.68 (1.25 to 2.24) | 1.45 (1.08 to 1.95) |
| DMPA Injection | 0.71 (0.34 to 1.49) | 0.62 (0.29 to 1.30) |
| None | 1.00 (0.92 to 1.09) | 1.03 (0.95 to 1.12) |
| History of polycystic ovarian syndrome | 0.81 (0.67 to 0.98) | |
| Calendar year contraception was started | 1.03 (1.01 to 1.04) | |
| Non-acne visits prior to index date, sqrt | 1.00 (0.98 to 1.03) | |
| Non-acne visits after index date, sqrt | 1.11 (1.09 to 1.14) | |
| Age | ||
| <20 years-old | [Reference] | |
| 20–24 years-old | 0.96 (0.87 to 1.07) | |
| 25–29 years-old | 1.03 (0.93 to 1.14) | |
| 30–34 years-old | 0.93 (0.84 to 1.03) | |
| 35–40 years-old | 0.72 (0.64 to 0.79) | |
HR: hazard ratio; CI: confidence interval; DMPA: depot medroxyprogesterone acetate; adj: adjusted
Discussion
We evaluated the association of contraception method on the development of incident clinical encounters for acne and acne severity among two groups: new contraceptive users, and individuals switching between contraceptive methods. In each of our analyses, women using a copper IUD or a levonorgestrel IUD were slightly more likely than those prescribed COCs to have incident or worsening acne. Women using the etonogestrel implant or the DMPA injection were slightly less likely to have incident clinical encounters for acne, although these contraceptives were not statistically significantly associated with treatment escalation.
It is important to emphasize that although we found some differences in the relative risk of acne between contraceptive methods, they were small. Differences in the absolute risk of acne are small as well. In our study, the frequency of patients seeking care for incident acne varied by contraception type and age as shown in Table 1, but was low overall (<5%), and the absolute difference in incident clinical encounters for acne between contraception classes was <1%. The risk of acne should be weighed alongside other important factors including individual patient preferences and medical history, the effectiveness of the method, bleeding profile, and potential side-effects. In addition, given the potential effects of multiple acne treatments on a developing fetus (i.e. topical retinoids, oral antibiotics, spironolactone, and isotretinoin),24 choosing an effective and patient-centered contraceptive option can help reduce the risk of fetal complications from treatments for acne.
In our analysis among individuals switching from COCs to other contraceptive methods, the hazard ratios for incident acne were generally higher for each contraceptive than they were in our analysis of new contraceptive users. These findings suggest that some of the observed associations in other studies between non-COC contraception classes and acne may be due to prior discontinuation of COCs before starting the non-COC contraception method, and that overall, large differences in the risk of acne between contraceptive classes are unlikely.14
Consistent with a prior randomized trial comparing a COC to a levonorgestrel IUD, we found that acne was more likely to be reported among users of the IUD.21 In contrast, our finding that the etonogestrel implant and DMPA injections were associated with a decreased risk of incident acne among new contraceptive users conflicts with several prior studies.14,20 In addition, these differences were not present in the treatment escalation or treatment switching analyses. While it is possible that these contraception methods may be protective against acne, it is important to consider the possibility of unmeasured confounding. Notably, women who receive the etonogestrel implant and DMPA injections are substantially less likely to have a history of acne, with odds ratios that are greater in magnitude than the associated E-values for the 95% confidence intervals (Table 3). We therefore urge caution in interpretation of these results because if an unmeasured confounder, such as acne that is not coded, was also associated with decreased risk of subsequent acne codes detected in our study, these findings could be biased.
This study has several limitations. The use of electronic claims data can be a powerful tool for understanding subgroup effects like contraceptive class, but can be limited by loss to follow-up, indication bias (e.g. patients with existing acne are more likely to receive COCs), and ascertainment bias. While ICD codes for acne have been validated in a dermatology population, the accuracy of these codes has not been extensively studied in non-dermatology populations.23 If dermatologists prescribe COCs more frequently than other contraceptives and subsequently code for incident acne more frequently than other providers, this could bias our results towards the null (i.e underestimation of the relative benefit of COCs over other contraceptives). Although we controlled for the number of visits before and after the index date to address ascertainment bias, it is possible that unmeasured confounders such as acne that is not coded could influence our observed results. To explore this potential issue, we performed a sensitivity analysis using E-values to quantify the potential magnitude of unmeasured confounding that would be required to influence our results.
Prior research has shown that COCs can reduce acne, and this study highlights that COCs are associated with a beneficial effect with respect to acne compared to other options and that the loss of a beneficial effect from COCs when switching to another method may partially explain why other contraception options have traditionally been felt to worsen acne. However, absolute differences between forms of contraception were small. Overall, patients should be reassured that COCs can reduce acne, and that there are unlikely to be major differences among other contraception classes on acne.
Supplementary Material
Funding Statement:
Funded in part through NIAMS 1P30AR069589-01. John Barbieri is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number T32-AR-007465 and receives partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania.
The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication
Footnotes
Financial Disclosure:
Dr. Mostaghimi receives consulting fees from Pfizer, hims, and 3derm. He has equity in Lucid and hims and receives licensing fees from Pfizer. He is on the medical advisory board for hims. He is a clinical trial investigator for Incyte, Lilly, Aclaris, and Concert. The authors did not report any potential conflicts of interest.
References:
- 1.Stathakis V, Kilkenny M, Marks R. Descriptive epidemiology of acne vulgaris in the community. Australas J Dermatol. 1997;38(3):115–123. [DOI] [PubMed] [Google Scholar]
- 2.Collier CN, Harper JC, Cafardi JA, et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008;58(1):56–59. [DOI] [PubMed] [Google Scholar]
- 3.Layton AM, Eady EA, Whitehouse H, Del Rosso JQ, Fedorowicz Z, van Zuuren EJ. Oral Spironolactone for Acne Vulgaris in Adult Females: A Hybrid Systematic Review. Am J Clin Dermatol. February 2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.George R, Clarke S, Thiboutot D. Hormonal therapy for acne. Semin Cutan Med Surg. 2008;27(3):188–196. [DOI] [PubMed] [Google Scholar]
- 5.Redmond GP, Olson WH, Lippman JS, Kafrissen ME, Jones TM, Jorizzo JL. Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial. Obstet Gynecol. 1997;89(4):615–622. [DOI] [PubMed] [Google Scholar]
- 6.Maloney JM, Dietze P, Watson D, et al. Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial. Obstet Gynecol. 2008;112(4):773–781. [DOI] [PubMed] [Google Scholar]
- 7.Koltun W, Maloney JM, Marr J, Kunz M. Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3mg administered in a 24/4 regimen: a pooled analysis. Eur J Obstet Gynecol Reprod Biol. 2011;155(2):171–175. [DOI] [PubMed] [Google Scholar]
- 8.Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012;(6):CD004425. [DOI] [PubMed] [Google Scholar]
- 9.Barbieri JS, James WD, Margolis DJ. Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: A retrospective analysis, 2004–2013. J Am Acad Dermatol. 2017;77(3):456–463.e4. [DOI] [PubMed] [Google Scholar]
- 10.van Vloten WA, van Haselen CW, van Zuuren EJ, Gerlinger C, Heithecker R. The effect of 2 combined oral Contraceptives containing either drospirenone or cyproterone acetate on acne and seborrhea. Cutis. 2002;69(4 Suppl):2–15. [PubMed] [Google Scholar]
- 11.Kelly S, Davies E, Fearns S, et al. Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study. Clin Drug Investig. 2010;30(5):325–336. [DOI] [PubMed] [Google Scholar]
- 12.Thorneycroft lan H, Gollnick H, Schellschmidt I. Superiority of a combined contraceptive containing drospirenone to a triphasic preparation containing norgestimate in acne treatment. Cutis. 2004;74(2):123–130. [PubMed] [Google Scholar]
- 13.Mansour D, Verhoeven C, Sommer W, et al. Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen. Eur J Contracept Reprod Health Care Off J Eur Soc Contracept. 2011;16(6):430–443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Lortscher D, Admani S, Satur N, Eichenfield LF. Hormonal Contraceptives and Acne: A Retrospective Analysis of 2147 Patients. J Drugs Dermatol JDD. 2016;15(6):670–674. [PubMed] [Google Scholar]
- 15.Darney P, Patel A, Rosen K, Shapiro LS, Kaunitz AM. Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials. Fertil Steril. 2009;91(5):1646–1653. [DOI] [PubMed] [Google Scholar]
- 16.Grunloh DS, Casner T, Secura GM, Peipert JF, Madden T. Characteristics associated with discontinuation of long-acting reversible contraception within the first 6 months of use. Obstet Gynecol. 2013;122(6):1214–1221. doi: 10.1097/01.AOG.0000435452.86108.59 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Ayadi AE, Diamond-Smith N, Harper C, Kohn JE, Rocca C. Young women’s experience of side effects and contraceptive discontinuation. Contraception. 2017;96(4):287–288. doi: 10.1016/j.contraception.2017.07.097 [DOI] [Google Scholar]
- 18.Fan G, Kang S, Ren M, et al. A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population. Contraception. 2017;95(4):371–377. [DOI] [PubMed] [Google Scholar]
- 19.Teal SB, Turok DK, Chen BA, Kimble T, Olariu AI, Creinin MD. Five-Year Contraceptive Efficacy and Safety of a Levonorgestrel 52-mg Intrauterine System. Obstet Gynecol. 2019;133(1):63–70. doi: 10.1097/AOG.0000000000003034 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Bahamondes L, Brache V, Meirik O, et al. A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls. Hum Reprod Oxf Engl. 2015;30(11):2527–2538. [DOI] [PubMed] [Google Scholar]
- 21.Suhonen S, Haukkamaa M, Jakobsson T, Rauramo I. Clinical performance of a levonorgestrel-releasing intrauterine system and oral contraceptives in young nulliparous women: a comparative study. Contraception. 2004;69(5):407–412. [DOI] [PubMed] [Google Scholar]
- 22.Optum.com. Data assets chart sheet. https://www.optum.com/content/dam/optum/resources/productSheets/5302_Data_Assets_Chart_Sheet_ISPOR.pdf. Accessed September 5, 2018.
- 23.Ejaz A, Malaiyandi V, Kim WB, Rogalska T, Alhusayen R. Validating the diagnostic code for acne in a tertiary care dermatology centre. Eur J Dermatol EJD. 2015;25(5):469–471. [DOI] [PubMed] [Google Scholar]
- 24.Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945–973.e33. [DOI] [PubMed] [Google Scholar]
- 25.Schmidt TH, Khanijow K, Cedars MI, et al. Cutaneous Findings and Systemic Associations in Women With Polycystic Ovary Syndrome. JAMA Dermatol. 2016;152(4):391–398. [DOI] [PubMed] [Google Scholar]
- 26.VanderWeele TJ, Ding P. Sensitivity Analysis in Observational Research: Introducing the E-Value. Ann Intern Med. 2017;167(4):268–274. [DOI] [PubMed] [Google Scholar]
- 27.von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet Lond Engl. 2007;370(9596):1453–1457. doi: 10.1016/S0140-6736(07)61602-X [DOI] [PubMed] [Google Scholar]
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