Evidence based commentary EBC Topic 1: Sept Aug 09

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1 Evidence based commentary EBC Topic 1: Sept Aug 09 Faculty Candidate Number: EXM00627 This evidence based commentary is submitted as part of the requirements for the Examination for Membership of the Faculty of Sexual and Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists Date completed: 25 Aug 2009 Word count: 1960 EXM00627 Page 1

2 SUMMARY OF KEY ISSUES Tracey is a healthy 19 years old with acne who is requesting reliable contraception, but she may also need protection from sexually transmitted infections (STIs). From her medical history she has no contraindication to any hormonal or nonhormonal methods of contraception and takes no drugs that might interact with contraception. Consideration should be given as to whether Microgynon 30 is affecting her acne and if changing to another combined oral contraception (COC) pill would improve her skin. The full range of contraceptive choices should be discussed with her including other combined hormonal methods, as well as progesterone-only and non-hormonal forms of contraception The effectiveness, side effects and acceptability of these forms of contraception and the possible effects on acne will need to be considered. Acne can be treated in a variety of ways and advice on these treatment options should be given. LITERATURE REVIEW Acne vulgaris is a common skin condition with an incidence of 80% in adolescence ¹. The peak age is 17 years, most resolving in their 20s although occasionally persisting into the 40s. Acne affects the pilo-sebaceous glands predominantly on the face, back and chest. Non inflammatory lesions (open and closed comedones) and inflammatory lesions (papules, pustules, nodules and cysts) are produced on a background of redness and greasy skin. Post inflammatory pigmentation and scarring can follow. The pathophysiology of acne includes increased sebum EXM00627 Page 2

3 production, bacterial proliferation particularly Propionibacterium acnes, hyperkeratosis leading to follicular plugging, inflammation and increased androgen levels in some women (most commonly associated with polycystic ovarian syndrome) ². Treatment options target one or more of these factors. Although often mild, acne can have a profound effect on the physical and psychosocial well being of patients ¹. Treatment can be topical or systemic, non-hormonal or hormonal, and more than one modality can be used concurrently ². Early treatment may prevent scarring³ and improvement can be seen in six weeks ⁴. If beneficial, treatment should be continued for at least four to six months. Topical preparations are indicated in mild to moderate acne. Comedones and inflamed lesions respond to benzoyl peroxide, azelaic acid or topical retinoid. Topical antibacterial preparations containing clindamycin or erythromycin are effective for inflammatory acne and can be combined with other topical treatments. Side effects of topical treatments include skin irritation, peeling and erythema. Oral treatments are used for moderate to severe acne or when topical therapy is not effective or difficult to apply. Tetracyclines, erythromycin and trimethoprim are useful for inflammatory acne but no antibiotic has been shown to have superior effectiveness ⁴. Side effects include gastrointestinal upsets, vaginal candidiasis, and reduced efficacy when commencing COC ⁵. The popularity of minocycline to treat acne has reduced following reports of side effects including hyper pigmentation and a lupus-like syndrome ⁶. Long term use of oral or topical antibacterials should be avoided if possible to minimise bacterial resistance ². EXM00627 Page 3

4 Co-cyprindiol is a hormonal treatment licensed for women with severe acne and it also provides effective contraception. It contains cyproterone acetate (CPA) which blocks androgen receptors so reducing sebum secretion ³. Co-cyprindiol is no more effective than oral antibacterials in treating acne ³. Concern that co-cyprindiol has an increased risk of venous thrombo-embolism (VTE) compared to other COCs led to recommendations from the Committee on Safety of Medicines that it should not be used solely for contraception, but could be used in women with severe acne resistant to antibiotics and then withdrawn 3-4months after the condition has resolved ⁷. However, women with androgen-related conditions have an inherently increased cardiovascular risk and some experts have questioned whether these are unnecessary restrictions ⁸. Severe or unresponsive acne can be treated with oral isotretinoin. This can only be prescribed by a dermatologist due to severe side effects and teratogenicity and women must use very effective contraception. A Cochrane review found that COC pills containing different progestogens (including CPA, levonorgestrel, norgestimate, gestodene, drosperinone, and desogestrel) all lead to improvements in acne ⁹. Few differences were found between the progestogens, with some studies producing conflicting results. Limited evidence suggested that CPA improved acne better than levonorgestrel. No comparison could be made between COCs and other acne treatments due to insufficient study data. The mechanism by which COCs are thought to improve acne is by reducing androgenic influence. Luteinising hormone is suppressed which reduces androgen synthesis, sex hormone binding globulin is increased thus reducing androgen EXM00627 Page 4

5 bioavailability and androgen receptors at the pilo-sebaceous unit are blocked so reducing sebum production ⁹. Other non-contraceptive benefits of COCs include their ability to regulate periods whilst reducing blood loss and menstrual pain. There is also a 50% reduction in the risk of ovarian and endometrial cancers⁵. Contraindications are categorised by the UK Medical Eligibility Criteria for Contraceptive Use¹⁰ and include risk factors for cardiovascular disease and VTE. The suitability of alternative methods of contraception should also be considered with reference to health risks¹⁰ and to non-contraceptive effects including acne. Longacting reversible contraception (LARC) methods such as intrauterine devices (IUDs), the intrauterine system (IUS), injectable contraceptives and implants have greater efficacy compared to pills (see Table 1) and are also more cost effective ¹¹. Table 1. Efficacy of Contraceptive Methods⁵ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ Efficacy rates Consistent and correct use Typical use Male condoms 98% 85% Female condoms 95% 79% Diaphragm/cervical cap with 92-96% 68-87% spermicide Combined oral contraceptive >99% 95% Progestogen-only pill >99% 92% Progestogen-only injection <0.4% at 2 years Progestogen-only implant <0.1% at 3 years Copper intrauterine device <2% at 5 years Intrauterine System <1% at 5 years LARC methods all have a long duration of action, do not rely on daily pill taking and do not interfere with sexual intercourse. EXM00627 Page 5

6 The efficacy of COC pills relies on regular daily use, and missed pills can lead to a reduction in the inhibitory effects on ovulation. The contraceptive patch and the vaginal ring are combined hormonal contraceptives that are changed weekly or monthly respectively. Progestogen-only methods of contraception commonly cause menstrual irregularities and women should be carefully counselled about this. There are fewer health risks than for COCs and they can often be used when oestrogens are contraindicated. Progestogen- only pills are less effective contraceptives than COCs and their effect reduces more quickly after a missed pill ¹². There is no evidence to link progestogen-only injections to an increase in acne ¹³. However, any effect on her skin will last until the injection wears off which may be months after the last injection. Side effects can include weight gain, menstrual irregularities including amenorrhoea and a delay in return of her natural fertility. Concern has been raised about the use of Depo-Provera in young women as it has been associated with a small loss of bone mineral density. Department of Health guidance suggests that it may only be used first line as long as other methods have been considered and it is reviewed every two years ¹³. Disruption of the normal bleeding pattern is common with the progestogen-only implant. Acne has been reported to improve, occur or worsen ¹⁴, but there is little evidence that it causes other non-menstrual side effects. The IUS contains levonorgestrel which promotes endometrial suppression so bleeding is substantially reduced ¹⁵. No significant differences in acne have been found between women with a copper IUD or IUS. EXM00627 Page 6

7 Non hormonal forms of contraception have no adverse effect on acne, but conversely have no beneficial effects. Barrier methods (condoms, caps, diaphragms) used as the sole method of contraception have considerably higher failure rates. Condoms afford some protection against STIs ¹⁶ and are readily available to buy without the need to see a health professional. Unlike other forms of contraception they are not available on prescription, and free supplies are restricted to Contraception and Sexual Health clinics or local condom distribution schemes. A copper IUD has no effect on acne. Discomfort at insertion, and the risk of heavier, more painful periods are potential barriers to patient acceptability. Women under 25 years have a higher risk of STIs so should be screened prior to insertion ¹⁵. The efficacy of emergency hormonal contraception (Levonelle 1500) is greater the earlier it is taken after unprotected sexual intercourse (UPSI). Insertion of an IUD is even more effective, can be fitted later after UPSI and can provide ongoing contraception. Many factors influence a woman s choice of contraception including familiarity with a method and which contraceptives are used by her peers¹⁷ ¹⁸ ¹⁹. Regulatory bodies monitor advertisements by the pharmaceutical industry. Recently the US Food and Drug Administration insisted on corrective advertisements for a new COC following misleading claims including the effect on acne ²⁰. Women want more information from health professionals about the range of contraception available and about factors such as the convenience, effectiveness, safety, side effects, invasiveness and discretion of different methods¹⁷ ¹⁸. Despite the recent trend to promote LARC methods, pill use can be unproblematic if managed well and is still popular ¹⁹. EXM00627 Page 7

8 APPLICATION OF EVIDENCE Tracey seeks advice about her acne. She has a normal body mass index, a regular menstrual cycle and no hirsuitism, and so is unlikely to suffer from hyperandrogenism or polycystic ovarian syndrome. Her concerns relating to acne should be acknowledged and the options for managing her acne and contraceptive needs should be discussed. Although her acne will get better in time, even without treatment, it may take years to do so. Tracey can be informed that Microgynon 30 may improve her acne. There is no firm evidence that changing to another COC would be more beneficial but she may want to try one containing a different progestogen as individual study results are conflicting. She has no increased risk factors for VTE so, depending on the severity of her acne, she could try co-cyprindiol until her acne resolves. Her mother suggests using condoms which have no adverse effect on her acne but unlike the COC have no benefit either. The failure rate is higher than for hormonal methods and if she decides to rely on condoms as her only method of contraception, she should be made aware of emergency contraception (both hormonal and IUD) and how to access it. She may want to keep some Levonelle 1500 at home so it can be taken immediately after any mishap with condom use ¹⁶. She is in a high risk age group for developing STIs and should be advised to use condoms for STI protection even if she also uses another more effective form of contraception. EXM00627 Page 8

9 As she does not want to get pregnant for 2 years, she could consider the more effective LARC methods, although these involve more invasive procedures and may cause menstrual changes. She may prefer to continue with Microgynon 30 and treat her acne with one of the topical anticomedonal or antibacterial treatments, or with an oral antibiotic. If she starts an oral tetracycline whilst on a COC she should use extra precautions for 3 weeks. Some acne treatments are available to buy over the counter, but she would need to consult with her General Practitioner for prescription-only medicines that are not prescribable at the contraception clinic. The effectiveness of any new treatment should be reviewed and Tracey warned that improvement may take months. Only if her acne became severe and unresponsive to other treatments would she need referral to a dermatologist for consideration of isotretinoin. IDENTIFICATION OF KNOWLEDGE GAPS AND SUGGESTIONS FOR FUTURE RESEARCH Studies of acne often have poor methodological qualities and standards of reporting, and use a variety of evaluation tools. Further research using well designed randomised trials and standardisation of outcome measures would help with interpretation and comparisons between different treatments and effects in different patient groups. There is a shortage of independently conducted trials researching COCs as many studies are supported by the pharmaceutical industry. The cost effectiveness of acne treatments has not been adequately evaluated, and there is limited data comparing COCs with other acne treatments. Further trials are EXM00627 Page 9

10 needed to ascertain whether the different progestogens in COCs have significantly different effects on acne and also on side effects such as VTE. The development of evidence based guidance would help health professionals who do not work as specialist dermatologists to give the best advice to patients with acne. REFERENCES 1. Purdy S and de Berker D. Clinical Review Acne. BMJ 2006;333: Haider A, Shaw JC. Treatment of Acne Vulgaris. JAMA. 2004; 292: [ assn.org/cgi/content/full/292/6/726?maxtoshow=&hits=10&hits=10&resultfo RMAT=&fulltext=acne+vulgaris&searchid=1&FIRSTINDEX=0&resourcetype=HW CIT] accessed 18/08/ Joint Formulary Committee. British National Formulary. Edition 56 London: British Medical Association and Royal Pharmaceutical Society of Great Britain. March Ozolins, M., Eady, E.A., Avery, A. et al. (2005) Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne. Health Technology Assessment 9(1), [ accessed 11/08/ Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit. First Prescription of Combined Oral Contraception. J Fam Plann Reprod Health Care 2003; 29: DTB (2009) Minocycline for acne an update. Drug and Therapeutics Bulletin : 7-8. EXM00627 Page 10

11 7. Committee on Safety of Medicines (CSM). Cyproterone acetate (Dianette ): risk of venous thromboembolism (VTE). Current Problems in Pharmacovigilance 2002; 28: Franks S, Layton A and Glasier A. Cyproterone acetate/ethinyl estradiol for acne and hirsutism: time to revise prescribing policy. Human Reproduction Vol.23, No.2 pp , 2008 doi: /humrep/dem379 [ s=10&resultformat=&fulltext=acne&searchid=1&firstindex=0&resourcet ype=hwcit] accessed 04/08/ Arowojolu AO, Gallo MF, Lopez LM, (et al). Combined oral contraceptive pills for treatment of acne. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD DOI: / CD pub3. [ ml] accessed 02/02/ Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit. UK Medical Eligibility Criteria for Contraceptive Use (UKMEC 2005/2006) National Institute for Health and Excellence (NICE). Long-acting reversible contraception. Clinical Guideline CG Faculty of Sexual & Reproductive Healthcare Clinical Effectiveness Unit Clinical Guidance. Progestogen-only Pills. November Faculty of Sexual & Reproductive Healthcare Clinical Effectiveness Unit Clinical Guidance. Progestogen-only Injectable Contraception. November Faculty of Sexual & Reproductive Healthcare Clinical Effectiveness Unit Clinical Guidance. Progestogen-only Implants. April EXM00627 Page 11

12 15. Faculty of Sexual & Reproductive Healthcare Clinical Effectiveness Unit Clinical Guidance. Intrauterine Contraception. November Faculty of Sexual & Reproductive Healthcare Clinical Effectiveness Unit Clinical Guidance. Male and Female Condoms. January Glasier A, Scorer J and Bigrigg A. Attitudes of women in Scotland to contraception: a qualitative study to explore the acceptability of long-acting methods. J Fam Plann Reprod Health Care 2008; 34(4): Say R and Mansour D. Contraceptive choice for young people. J Fam Plann Reprod Health Care 2009; 35(2): Williamson LM, Buston K and Sweeting H. Young women s continued use of oral contraceptives over other hormonal methods: findings from a qualitative study. J Fam Plann Reprod Health Care 2009: 35 (3): Tanne JH. Bayer to spend $20m to correct misleading advertising for oral contraceptive Yaz. BMJ 2009; 338:b674. [ its=10&resultformat=&fulltext=yaz&searchid=1&firstindex=0&sortspec =date&resourcetype=hwcit] accessed 04/08/2009. EXM00627 Page 12