A Primary Care Framework for Classifying and Managing Acne Vulgaris: Focus on Inflammatory and Post-Adolescent Acne
ABSTRACT: Acne vulgaris is the most common skin condition in the United States. Although patients tend to go to dermatologists to treat their acne, particularly when it progresses and becomes inflammatory, many cases can be just as efficiently managed in the primary care setting. This article provides an overview of acne vulgaris, with a focus on inflammatory and post-adolescent acne, and outlines a framework that primary care physicians can use to effectively treat these patients.
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Acne vulgaris, simply referred to as acne, is a multifactorial disorder of the pilosebaceous unit. It is the most common skin condition in the United States, affecting approximately 40 to 50 million individuals annually.1 A patient’s clinical picture can vary greatly from mild comedonal acne (ie, noninflammatory disease) to fulminant disease. The psychological impact can be intense, and the economic costs of treatment can be considerable. Increasing knowledge about the pathogenesis of acne has led to the development of numerous effective treatment regimens that can be tailored to each patient. The lack of standardization for grading acne severity and measuring treatment outcomes has made systematic interpretation of the literature difficult; however, quality evidence-based literature in the field of acne is growing.2,3 This article provides a framework that primary care clinicians can use to categorize and manage acne. The focus is on inflammatory and post-adolescent acne, as these are the most common acne subtypes for which patients seek care, and they can usually be appropriately managed in the primary care setting.
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Epidemiology and Pathogenesis of Acne
Acne typically begins at puberty and is often the first sign of increased sex hormone production, particularly testosterone. It is primarily considered a disease of teenagers—with 85% to 90% of all teenagers having some degree of acne.4 Although acne generally resolves by age 25 years, there is great variability in the age of onset and resolution. One systemic review reported acne to persist into the 20s and 30s in around 64% and 43% of individuals, respectively.5
In addition, acne may emerge in both men and women in the decades beyond adolescence, even manifesting during the 3rd or 4th decades of life and sometimes persisting into the 5th decade. In women, this type of acne often flares prior to menses and is commonly referred to as female hormonal acne; however, because the condition is not always associated with menses, even in women, it is preferable to use the term post-adolescent acne to describe acne that persists after age 25 years.
The following 4 main factors contribute to the pathogenesis of acne6:
•Excess sebum production, which results from androgen-mediated stimulation of the sebaceous glands;
•Abnormal keratinization of the follicles, leading to plugging and comedone formation;
•Colonization by Propionibacterium acnes, a gram-positive, nonmotile bacterium that forms part of the normal flora of the skin; and
•Inflammation of the follicle and the surrounding dermis, which may in part be caused by P acnes.
P acnes may contribute to the inflammatory response in several ways. First, it may stimulate the production of a variety of contributory compounds, including enzymes that may promote follicular rupture, surface proteins that play a role in antigenicity, heat shock proteins that promote inflammation via the innate immune system, and porphyrins that may contribute to adjacent tissue damage.7,8 In addition, toll-like receptor 2, a component of the innate immune system, binds to P acnes and triggers the release of proinflammatory cytokines, including interleukin (IL)-8 and IL-12.9 These cytokines attract neutrophils, which release lysosomal enzymes at the site of inflammation, leading to rupture of the follicular epithelium and further inflammation.9
The precursor to the manifestation of visible acne is formation of the microcomedone, a subclinical lesion caused by abnormal regulation of cells within the hair follicle. This progresses to comedone formation when corneocytes (ie, terminally differentiated keratinocytes) are retained and accumulate in the follicular ostium instead of being extruded. This can result from increased cell cohesiveness, which is modulated by lamellar granules, cell wall membranes, and epidermal lipids, and from accelerated production of corneocytes, which creates a bottleneck phenomenon.
When the follicular opening is small or closed, the result is a closed comedone. These typically appear white upon inspection and are referred to as whiteheads. When the follicular opening is dilated, the result is an open comedone. These typically appear as blackheads, with the black discoloration occurring from lipid oxidation within the debris.10
As the corneocytes continue to accumulate, multiple factors can lead to localized inflammation, as described earlier, resulting in an inflammatory papule (ie, pimple). This may then lead to follicular rupture, resulting in the appearance of nodular and cystic lesions. Of note, although inflammation was thought to largely occur towards the later stages of acne development, more recent evidence suggests that specific cascades of inflammation occur early, even before or concurrently with microcomedone formation, and continue during resolution into the scarring phase.11
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Patient Assessment
Prior to instituting acne therapy, it is important to obtain a standard history of present illness and to assess and review all of the patient’s prescription and over-the-counter (OTC) regimens for acne and his or her clinical responsiveness to them. A menstrual and oral contraceptive history is important in determining hormonal influences on acne in women. In men, a medication history to check for any offending agents, such as corticosteroids or testosterone replacement, is essential. Finally, a physical examination directed at lesion morphology should be undertaken, examining for comedones, inflammatory papules or pustules, nodules, cysts, scarring, and other skin lesions and anomalies, as these findings will help determine the initial treatment regimen (Table).
Physical characteristics. Closed comedones, or whiteheads, are typically small (approximately 1 mm) skin-colored papules with no apparent follicular opening or associated erythema. Open comedones, or blackheads, are dome-shaped papules with a conspicuous dilated follicular outlet. The inflammatory lesions of acne originate with comedo formation but then expand to form papules, pustules, nodules, or cysts. Erythematous papules range from 1 mm to 5 mm in diameter. Pustules are similar in size and filled with white pus. Nodules are larger (>1 cm) and even more inflamed, indurated, and tender than papules or pustules. Cysts are deep-seated lesions and filled with pus and/or serosanguineous fluid.10
Classification. In addition to determining the type of skin lesion, acne should be further subtyped to establish proper treatment. One such method that may be useful for primary care physicians is to classify acne by severity using one of the following categories: mild comedonal, mild to moderate inflammatory, moderate to severe inflammatory, and nodulocystic acne (severe). Figures 1-3 shows the latter 3 classifications of acne.
Figure 1. Example of mild-to-moderate inflammatory acne.
Figure 2. Example of moderate-to-severe inflammatory acne.
Patients with mild comedonal acne present to physicians for treatment less frequently because self-treatment with OTC remedies is often sufficient. Patients who seek consultation for mild comedonal acne are best treated with a topical retinoid. These patients rarely require complex regimens or consultation. At the other end of the spectrum is severe nodulocystic acne, which is better treated by a dermatologist, as these specialists are more experienced in managing severe skin conditions. Subsequently, this article does not further address mild comedonal acne or severe acne.
In our experience, the most common stage at presentation to primary care practices is mild to moderate inflammatory acne; however, differentiating between mild, moderate, and severe inflammatory acne can be subjective. When making the determination, it is important to ask the patient to characterize his or her acne on this basis, as individual perception is a critical factor when deciding on therapy. In addition, taking an approximate lesion count can help to more objectively classify acne into an appropriate category.
One possible metric is to consider less than 15 inflammatory lesions as mild to moderate acne, more than 15 lesions as moderate to severe acne, and the presence of multiple nodules and cysts as severe nodulocystic acne. Any cases of severe nodulocystic acne should be referred to a dermatologist for treatment. Although it is often impractical to count individual lesions, a good clinical examination in combination with an approximate lesion count and a patient’s self-assessment can help categorize acne into one of the 4 aforementioned classifications.
For example, a patient who has lesions consisting primarily of comedones and only a few papules and pustules (<15) could be classified as having mild to moderate inflammatory acne. In contrast, if this same patient feels that his or her acne is severe and he or she is experiencing a negative psychosocial impact from it, then it might be reasonable to “upgrade” the classification to moderate to severe inflammatory acne and consider more aggressive initial treatment.
Figure 3. Example of post-adolescent female hormonal acne.
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Differential Diagnosis
Several other skin disorders may be confused with acne, but the differential diagnosis of acne is modest in scope and readily distinguished by patient age, lesion morphology, lesion distribution, and the presence of risk factors for mimickers of acne vulgaris. For example, predominantly comedonal acne needs to be differentiated from acne-like eruptions caused by follicular occlusions, which include pomade acne (ie, a form of acne that typically appears on the areas of skin that most commonly come into contact with hair styling products; for example, the scalp, forehead, and temples) and occupational acne (ie, results from consistent occupational exposure to a variety of chemicals, including petroleum and its derivatives, coal-tar products, and halogenated aromatic compounds; the latter type being referred to as chloracne). Other differential diagnoses include rosacea, periorificial dermatitis, pseudofolliculitis barbae, and drug-induced acne.
•Rosacea is a common inflammatory disorder that may present with papules, pustules, telangiectasias (ie, spider veins), or erythema involving the central face (Figure 4). Rosacea tends to manifest at a later age than acne, and the lack of comedones (the primary lesion of acne) is a distinguishing feature. The papular component of rosacea favors the malar region, chin, and forehead. The presence of telangiectasias and a history of easy flushing can also aid in establishing the correct diagnosis.
•Periorificial dermatitis, as the name implies, usually involves areas around the mouth and eyes, and is often triggered or exacerbated by prolonged use of topical corticosteroids. The skin immediately adjacent to the vermillion border is usually spared. This disorder is most often seen in young women.
•Pseudofolliculitis barbae, also colloquially referred to as razor bumps or shaving bumps, consists of inflammatory papules and pustules on the neck and facial beard area. It occurs primarily in men of African descent due to their coarse curly hair. The condition results from reentry of the free ends of short, cut beard hairs into the skin.
•Drug-induced acne, also referred to as acne medicamentosa, usually presents as monomorphous papules and pustules, which tend to favor the trunk. Multiple drugs may cause these acneiform eruptions, including topical or systemic corticosteroids (Figure 5), lithium, and epidermal growth factor inhibitors, among others.12
Figure 4. Example of rosacea.
Treatments for Inflammatory Acne
Many agents are available to treat inflammatory acne, including topical and oral agents, depending on the severity of the patient’s skin condition.
Topical retinoids. These agents represent a mainstay of acne treatment because they reduce microcomedone formation and exert anti-inflammatory effects through a number of pathways (eg, downregulating toll-like receptors), and normalize follicular epithelial differentiation and keratinization.13 Retinoids exert these effects by binding to 2 nuclear receptor families within keratinocytes: the retinoic acid receptors and the retinoid X receptors.14 Receptor binding leads to gene transcription, affecting growth and differentiation of cells in the skin.
Three major retinoids are commercially available: tretinoin, a carboxylic acid form of vitamin A and first-generation agent; adapalene, a retinoid-like compound and third-generation agent; and tazarotene, an acetylenic retinoid and third-generation agent. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment for mild comedonal acne. Retinoids are the backbone of all acne regimens, including for more severe cases, and should also be used as maintenance therapy, as these agents accelerate the resolution of acne-induced postinflammatory hyperpigmentation.
In general, a 6- to 12-week course of topical retinoid treatment is recommended for mild to moderate acne. During this time, these agents may cause a mild flare of acne before providing any skin improvement. Patients should be warned of this effect to prevent noncompliance with therapy. The main side effect of topical retinoids is irritation, which can be reduced with alternate-day dosing. Tazarotene is generally regarded as the most effective retinoid but also causes the most irritation. For example, a 2001 randomized trial showed that tazarotene 0.1% gel was more effective than tretinoin 0.025% gel in reducing the open comedo count (P≤.05), the total noninflammatory lesion count (P≤.05), and the total inflammatory lesion count (did not reach statistical significance).15 Although tazarotene was associated with increased irritation, other side effects, such as peeling, erythema, dryness, burning, and itching, never exceeded trace levels.15 Adapalene has less irritancy than tretinoin and is light-stable and resistant to oxidation by benzoyl peroxide.16,17 These characteristics allow adapalene to be combined with benzoyl peroxide, an antibiotic and skin-peeling agent, in the same product (ie, Epiduo). This combination product may be more convenient for patients and enhance compliance.
There is extensive evidence for the efficacy of topical retinoids in the treatment of acne. A 12-week randomized trial that included 60 acne patients treated with tretinoin 0.05% solution, tretinoin 0.025% solution, or placebo showed greater reductions in acne lesions in both tretinoin arms.18 A larger 12-week trial that involved 653 patients who were randomly assigned to receive adapalene 0.3% gel, adapalene 0.1% gel, or vehicle gel showed that adapalene was more effective than the vehicle gel alone.19 In addition, pooled results of 2 randomized, controlled trials that included a total of 847 acne patients treated with tazarotene 0.1% cream or vehicle for 12 weeks showed a significantly greater reduction in both noninflammatory and inflammatory lesion counts (P<.001) in patients receiving tazarotene.20
Figure 5. Example of corticosteroid-induced acne.
Benzoyl peroxide. This agent is an organic compound that has been found to be a safe and effective OTC acne treatment. It works by reducing P acnes numbers, suppressing the growth of these bacteria, and killing them without inducing bacterial resistance. It exerts these effects partially by bringing oxygen under the skin as it decomposes, giving it potent bactericidal activity in the sebaceous follicles.21 It also inhibits triglyceride hydrolysis, decreases inflammation of acne lesions, and has keratolytic and comedolytic activities.22
Lower concentrations (2.5% or 5%) of benzoyl peroxide are recommended, as they are less irritating and there is no clear evidence that stronger preparations are more effective.23 Although benzoyl peroxide can be used as a single-drug therapy, its activity is enhanced when used in combination with other medications.
Several studies suggest that the efficacy of benzoyl peroxide can be enhanced when used in combination with topical retinoids or topical antibiotics.24 The superiority of combination treatments is likely because benzoyl peroxide can prevent development of antibiotic resistance during treatment. The main adverse effect of benzoyl peroxide is an irritant contact dermatitis, which may be mitigated by using lower concentrations, less irritating vehicles (eg, changing from gel to cream), or alternate-day dosing. Patients and their parents should be aware that benzoyl peroxide can bleach clothing, towels, bed linens, and even hair.25,26
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Topical antibiotics. Also considered safe and effective, these commonly prescribed agents improve acne by acting directly on P acnes colonization and inhibiting the proinflammatory effects of these bacteria on comedogenesis. Commonly used topical antibiotics include various formulations of clindamycin and erythromycin.
Some clinical trials have suggested a clear association between P acnes resistance to an antibiotic and poor therapeutic response.27 For this reason, monotherapy with topical antibiotics is generally not recommended. Instead, a combination of clindamycin and benzoyl peroxide (eg, Duac) is a preferable choice because it has proven efficacy and tolerability and prevents the development of antimicrobial resistance.
In well-designed clinical trials that include patients with mild to moderately severe acne, the efficacy of once- or twice-daily clindamycin/benzoyl peroxide in reducing inflammatory lesion counts was greater than that of clindamycin alone, benzoyl peroxide alone, or tretinoin plus clindamycin, and not significantly different from that of erythromycin/benzoyl peroxide.28 In addition, an evidence-based review indicated that compliance is likely increased with once-daily combination products.29
Sodium sulfacetamide is a less frequently used topical antibiotic. It is a well-tolerated sulfa-based antibiotic that is thought to restrict the growth of P acnes.
Miscellaneous topical agents. Some other topical agents commonly used to treat acne include salicylic acid and azelaic acid, which may be used alone but are generally more effective when used in combination products. Salicylic acid is a widely used comedolytic and mild anti-inflammatory agent that is available in numerous OTC preparations. Clinicians rarely prescribe it because it is not as efficacious as retinoids or benzoyl peroxide.30
Azelaic acid has been shown to be effective against inflammatory and comedonal acne by inhibiting the growth of P acnes and reversing the altered keratinization of follicles affected by acne. It also may help lighten postinflammatory hyperpigmentation.
Oral antibiotics. When topical agents are insufficient to control acne, oral antibiotics may be prescribed. These agents are generally reserved for moderate or severe inflammatory acne. Commonly prescribed oral antibiotics include tetracyclines, clindamycin, azithromycin, and erythromycin; however, concerns about antibiotic resistance and associated decreased efficacy with the latter 3 agents make tetracycline the preferred oral antibiotic treatment for acne. The only exception to this concerns pregnant women, in whom tetracyclines are contraindicated, making erythromycin the preferred agent for this population.
In addition to suppressing the growth of P acnes, tetracyclines have intrinsic anti-inflammatory properties. Among the tetracyclines, tetracycline is the safest and cheapest choice, but requires frequent dosing on an empty stomach, increasing the risk of nausea and vaginitis.
Because the efficacy of oral tetracycline and erythromycin has reportedly diminished over the past 4 decades, a variety of other agents have been used to treat inflammatory acne; these include minocycline, a semisynthetic derivative of tetracycline, and doxycycline, a synthetic derivative of tetracycline.31 Subsequently, some clinicians have come to consider minocycline as the most effective oral antibiotic for acne, but high-level evidence to support it superior efficacy is lacking. In addition, minocycline is associated with severe side effects, including vertigo, lupus-like syndromes, hepatitis, and pigmentary changes. Nevertheless, it can be tried for patients whose P acnes become resistant to doxycycline.
When doxycycline is prescribed, it is generally at doses of 50 mg to 100 mg taken once or twice daily. Photosensitivity reactions and gastrointestinal upset are common with this medication. Subantimicrobial dose doxycycline (20 mg twice daily) is also available. This agent is a nonantibacterial formulation of doxycycline, which works by modulating the host response, including via mechanisms unrelated to its antibacterial properties.32 Studies have found it to be more effective than placebo for treating acne vulgaris33; however, head-to-head studies comparing subantimicrobial dose doxycycline and traditional dose doxycycline are lacking. Further studies are necessary before a recommendation can be made to choose subantimicrobial dosing over traditional doses of doxycycline for the treatment of acne vulgaris.
All tetracyclines should be avoided in children younger than 11 years because they can stain growing teeth. The authors usually prefer doxycycline as first-line therapy when factoring in cost, safety, efficacy, and dosing schedules.
Regardless of which oral antibiotic is prescribed, it can and likely should be used in conjunction with topical benzoyl peroxide, as this may help prevent the development of bacterial resistance. However, the concomitant use of topical and oral antibiotics should be avoided, as this promotes P acnes resistance, has little effect on efficacy, complicates treatment regimens, and is likely to decrease compliance.
Spot treatment. This refers to the application of medicines to individual inflammatory lesions, sparing uninvolved areas. When using topical retinoids, it is advisable to treat the entire affected area (eg, entire face) because the primary mechanism of action of these medications focuses on preventing comedogenesis. Although topical antimicrobials/benzoyl peroxide combinations can be used directly on individual lesions for a presumed anti-inflammatory effect, these medications also have activity on noninflamed lesions and are therefore most effective if applied to the entire affected area.
When a quick response on an individual lesion is desired, intralesional injections of corticosteroids can be used. A large inflammatory pustule can be injected with 0.1 cc to 0.2 cc of triamcinolone acetonide in concentrations of 2.5 mg/mL to 5 mg/mL using a 30-gauge needle. Intralesional injections have the advantage of rapid resolution of troublesome lesions and low cost. Disadvantages include pain with injection and a risk for atrophy and telangiectasias in treated areas. Intralesional corticosteroid injections are not suitable as a primary form of acne treatment due to the need for frequent visits and the increased risk for potential side effects.34
Progression of treatments. With so many treatments at clinicians’ disposal, it may be unclear which treatment regimens to use. Patients with mild comedonal acne are best treated with topical retinoid monotherapy. When the condition progresses to mild to moderate inflammatory acne, a topical antibiotic and benzoyl peroxide need to be added. When acne becomes moderate to severe, it is best treated with an oral antibiotic and benzoyl peroxide in addition to a topical retinoid.
As previously noted, patients with severe nodulocystic lesions should be referred to a dermatologist for consultation, as these lesions can lead to disfigurement and isotretinoin and other more aggressive alternative treatment regimens may be warranted. The aforementioned treatment recommendations for inflammatory acne make use of 3 agents, a practice referred to as triple therapy.
The current literature provides sufficient evidence to support this practice; however, given the concerns for compliance with such a complicated regimen, fixed-dose combination regimens can be used in situations where convenience of therapy is more important to the patient than cost.
Monitoring Treatment Response and Compliance
Improvement of acne with any of the aforementioned medicines often takes up to 3 months. One approach for monitoring therapeutic effectiveness is to re-evaluate a patient between 8 and 12 weeks. The rationale for this timeline is that it takes about 8 weeks for a microcomedone to mature, so therapy must be continued beyond this duration to assess efficacy. In addition, many clinical trials evaluating acne regimens are designed with 12-week clinical endpoints, making this a reasonable time period to evaluate for improvement in the clinical setting. When feasible, it is helpful to take photographs at baseline to obtain an objective measurement of progress.
If satisfactory improvement is not seen after 2 to 3 months, the first step is to verify patient adherence to treatment. If adherence to treatment is adequate, more aggressive therapy may be warranted. For example, if a patient does not improve with combined topical therapy, the logical next step would be to substitute an oral antibiotic, such as doxycycline for the topical antibiotic. Patients who do not adequately respond to initial or adjusted therapy should be referred to a dermatologist for further evaluation and treatment.
Conclusion
Acne vulgaris is encountered in many patients on a daily basis. Although common, it can have a devastating psychosocial impact on patients and present a significant treatment challenge to the clinician; however, many cases of inflammatory and post-adolescent acne can be effectively treated in the primary care setting using the methods described in this article. ■
In the United States, the primary drugs used to treat postadolescent acne include:
• Androgen receptor blockers (ie, flutamide, spironolactone).
These agents block the effect of androgens on the sebaceous gland.
Flutamide is a nonsteroidal androgen receptor blocker used to treat prostate cancer that has also been effective in treating acne. One study found an 80% improvement in acne with flutamide 250 mg daily,36 whereas another study showed a 96% improvement.37 Side effects include breast tenderness, gastrointestinal upset, hot flashes, and decreased libido. In addition, fatal hepatotoxicity has been observed in some patients; thus, regular liver function tests are necessary while patients are taking this medication.
With regard to pregnancy, flutamide has been assigned a category D by the FDA, as it is known to cause fetal harm. As a result, it should not be used in pregnant or lactating women or in those looking to conceive. When used in women, it should be done in combination with an oral contraceptive.
Spironolactone has been used for more than 30 years as a treatment for acne and hirsutism. It achieves its antiandrogen effects through several mechanisms, including competing with testosterone and dihydrotestosterone for androgen receptors, halting the conversion of androstenedione to testosterone, inhibiting 5-alpha reductase, and increasing the level of SHBG.36,38,39
Three relatively small randomized, controlled trials have demonstrated that spironolactone (at varying doses) is an effective acne treatment.39,40 The usual dosage ranges from 50 mg to 200 mg daily, and it should be started at the lower 50 mg dose and titrated up to response in an effort to minimize side effects.
Although generally well-tolerated by women, side effects include menstrual irregularities (most common adverse effect), breast tenderness, headache, fatigue, and potential hyperkalemia. The hyperkalemia associated with spironolactone has been shown to be clinically insignificant in the absence of cardiac or renal disease; thus, monitoring potassium levels is generally unnecessary.
Spironolactone is considered a category C medication by the FDA, so should not be prescribed to pregnant or lactating women or to those looking to conceive, as there is the risk of fetal teratogenicity (feminization of a male fetus) and potential of irregular spotting. To protect against fetal harm, this agent should only be used in conjunction with an oral contraceptive for any women of childbearing age.
• Combined oral contraceptive pills (OCPs).
These agents suppress ovarian androgen production and increase sex hormone binding–globulin (SHBG), thereby reducing the amount of free testosterone. It is the estrogen component of oral contraceptives that stimulates production of SHBG; thus, progestin-only formulations are not effective. In fact, the androgenic activity of most progestins, with the exception of drospirenone, could potentially worsen acne.
Many combined OCPs have been used to treat acne, but the FDA has only approved 3 for this purpose: Estrostep Fe (ethinyl estradiol 20, 30, 35 ug/norethindrone 1 mg), Ortho Tri-Cyclen (ethinyl estradiol 35 ug/norgestimate 180, 215, 250 ug), and Yaz (ethinyl estradiol 20 ug/drospirenone 3g). The efficacy of both Estrostep and Ortho-Tri-Cyclen has been proven in multicenter, randomized, double-blind, placebo-controlled trials.41,42
In reality, most combination oral contraceptives are effective in treating acne and there is insufficient evidence to recommend one OCP over another. Although the results of a few randomized trials have suggested slightly greater benefit with Yaz than Ortho Tri-Cyclen, additional high-quality trials are necessary to confirm these results.43 It should be noted that the use of drospirenone has declined in light of recent reports of increased risks of venous thromboembolism with this medication. For example, a systematic review showed a rate ratio of venous thromboembolism among drospirenone-containing OCP users as ranging from 4.0 to 6.3 when compared with nonusers of OCPs, and from 1.0 to 3.3 when compared with levonorgestrel-containing OCP users.44
Despite such reports, the American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice does not recommend against prescribing drospirenone-containing OCPs, but it does make the following recommendations: (1) physicians should communicate the minimally increased risk to their patients; (2) drospirenone-containing OCPs should still be made available to patients; (3) these agents should not be discontinued if they are well tolerated and working; and (4) before prescribing or recommending these agents, physicians should consider all of their patients’ risk factors for venous thromboembolism.45
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