RESEARCH J Fam Plann Reprod Health Care: first published as 10.1136/jfprhc-2015-101202 on 20 April 2016. Downloaded from Prescribing patterns of combined hormonal products containing cyproterone acetate, levonorgestrel and drospirenone in the UK 1 Pharmacoepidemiologist, 1,2 3 1 Spanish Centre for Lucía Cea-Soriano, Mari-Ann Wallander, Luis Alberto García Rodríguez Pharmacoepidemiologic Research (CEIFE), Madrid, Spain 2Department of Preventive Medicine and Public Health, Faculty of Medicine, ABSTRACT Complutense University of Background There are limited data to show the Key message points Madrid, Madrid, Spain levels of prescribing of combined oral 3Professor, Department of Public contraceptives (COCs) and other hormonal ▸ Health and Caring Science, There are limited data to show the Uppsala University, Uppsala, products containing estrogen/progestogen levels of prescribing of estrogen/pro- Sweden combinations that may be outside the product gestogen combinations that may be licence. Correspondence to outside the approved product licence. Dr Lucía Cea-Soriano, Aims To determine the diagnosis/indication ▸ In keeping with UK guidelines, the Pharmacoepidemiology, recorded at the time of prescription of level of cyproterone acetate/ethinyles- Spanish Centre for cyproterone acetate/ethinylestradiol (CPA/EE) and tradiol (EE) prescribing for contracep- Pharmacoepidemiologic Research two COCs, levonorgestrel/EE (LNG/EE) and (CEIFE), Almirante 28, tive use was low. Madrid 28004, Spain; drospirenone/EE (DRSP/EE). ▸ The combined oral contraceptives levo- [email protected] Design and setting Retrospective study using a norgestrel/EE and drospirenone/EE were copyright. primary care database, The Health Improvement commonly prescribed for reasons other Received 23 February 2015 Network (THIN). Revised 2 March 2016 than to provide contraception. Accepted 16 March 2016 Methods Women in THIN aged 12–49 years Published Online First prescribed CPA/EE, LNG/EE or DRSP/EE in 2002– 20 April 2016 2010 were identified. Overall use of each product and proportion of new users each year were INTRODUCTION determined. Among new users, database codes In the 50 years since they were first intro- were analysed to infer the reason for prescription. duced, combined oral contraceptives Results The proportion of new users of each (COCs) have remained one of the most product in 2002 and 2010, respectively, were: popular forms of contraception. In 2008/ http://jfprhc.bmj.com/ LNG/EE, 2.03% and 2.40%; CPA/EE, 0.45% and 2009, a UK survey conducted by the 0.27%; and DRSP/EE, 0.27% and 0.56%. Most Office of National Statistics reported that new users prescribed CPA/EE had a record of 25% of women aged 16–49 years were acne (51.0% and 79.2% in 2002 and 2010, using an oral contraceptive pill.1 In respectively) or hirsutism (3.0% and 5.0% in April–June 2010, 1.2 million prescrip- 2002 and 2010, respectively); the proportion of tions for COCs containing 30–40 mg new users with a record only for contraception ethinylestradiol (EE) were dispensed in on October 2, 2021 by guest. Protected decreased from 32.9% in 2002 to 8.6% in England.2 It is well recognised that COCs ▸ http://dx.doi.org/10.1136/ 2010. Among new users prescribed DRSP/EE or may be prescribed for purposes other jfprhc-2016-101585 LNG/EE in 2010, 43.2% and 30.8% of women, than contraception, but prescribing pat- respectively, did not have a record indicating use terns for the non-contraceptive uses of for contraception. COCs are poorly documented. Conclusions Adherence to prescribing Studies have shown that some COCs guidelines for CPA/EE has improved over time. A can be effective in the treatment of acne.3 substantial proportion of women using DRSP/EE Some guidelines also recommend that To cite: Cea-Soriano L, or LNG/EE had records for hormone-responsive Wallander M-A, García these products can be used to manage Rodríguez LA. J Fam Plann conditions only, suggesting that many women menstrual disturbances such as dysmenor- Reprod Health Care were prescribed these therapies for non- rhoea and menorrhagia, although the – 2016;42:247 254. contraceptive use. evidence for effectiveness in these Cea-Soriano L, et al. J Fam Plann Reprod Health Care 2016;42:247–254. doi:10.1136/jfprhc-2015-101202 247 Research J Fam Plann Reprod Health Care: first published as 10.1136/jfprhc-2015-101202 on 20 April 2016. Downloaded from – conditions is based largely on observational studies.4 6 using data from this source.14 The study population In fact, some formulations of COCs, such as levonor- consisted of women in THIN aged 12–49 years gestrel (LNG) and EE (LNG/EE), are also approved between 1 January 2002 and 31 December 2010. To for the treatment of “recognised gynaecological indi- be eligible for inclusion in the study, women were also cations for such oestrogen/progestogen combina- required to have been enrolled with their GP for at tions”.7 In addition, women who do not require least 5 years and to have had a computerised prescrip- contraception may be prescribed hormonal contracep- tion history of at least 1 year. tives solely for these non-contraceptive purposes.8 The use of COCs for the treatment of Ascertainment of user groups hormone-responsive conditions such as acne or hirsut- To ascertain the number of women prescribed each ism, which could be outside the approved licences, treatment in each calendar year during the period – may be common in clinical practice;5 9 however, there 2002–2010 (inclusive), women who met the above are limited data to show how frequently COCs are criteria and who had been prescribed CPA/EE, LNG/ prescribed for such use. EE or DRSP/EE were identified. The date of first pre- In the UK, the combination of cyproterone acetate scription during the study period was defined as the (CPA) and EE (CPA/EE) is indicated for the treatment index date. LNG/EE is available under several brand of moderate-to-severe acne related to androgen sensi- names, in which the dose of EE may be fixed (mono- tivity (that has not responded to oral antibiotic phasic) or variable (phasic). All formulation types therapy) and/or hirsutism in women of reproductive were included. age. This combination is also an effective contracep- tive,10 but marketing approval has not been sought Analysis of new and existing users for this indication. In many cases, acne and hirsutism Each user group was stratified according to previous occur as a result of elevated levels and/or increased prescription contraceptive use. New users were identi- action of circulating androgens, for example in poly- fied as having no record of using any of the study cystic ovary syndrome (PCOS); CPA/EE has the add- treatments before the year of interest, whereas existing itional effect of helping to control the menstrual users had records showing prescription of these pro- irregularities frequently associated with this condi- ducts before the year of interest. New users of each 11 tion. Recently, concerns have been raised in France treatment were further stratified into first-time (naïve) copyright. regarding the risk of venous thromboembolism and users and previous (non-naïve) users. Naïve users had the off-label use of CPA/EE as a contraceptive.12 A no record of previous use of any hormonal contracep- subsequent review by the European Medicines Agency tive before the index date, whereas non-naïve users found that the balance of benefits and risks of treat- had previously received a hormonal contraceptive ment with CPA/EE remained positive, provided that other than the study treatment. several measures were taken to minimise the risk of For each new user, we identified diagnoses or indi- thromboembolism, such as avoiding combination with cations relevant to the prescribing of these treatments other hormonal contraceptives.13 during the earliest (2002) and most recent year The aim of this study was to determine the diagno- (2010) of the study. sis or indication recorded at the time of prescription of CPA/EE and two COCs, using data from a UK Identification of the diagnosis or indication recorded at http://jfprhc.bmj.com/ primary care database, The Health Improvement time of CPA/EE prescription Network (THIN). We examined the patterns of use of We conducted computerised searches of the medical CPA/EE, LNG/EE and drospirenone (DRSP) and EE records of new CPA/EE users, whereby defined search (DRSP/EE; first marketed in the UK in 2002 and only terms were applied individually in a ranked order. licensed for contraception). For each year of the study, Searches were restricted to the 90 days before and we also determined the annual proportion of new after the index date. CPA/EE is approved for the treat- users and the proportion of overall use (i.e. the total ment of acne (with or without seborrhoea) and/or hir- on October 2, 2021 by guest. Protected of new and existing users) among women aged 12– sutism relating to androgen sensitivity in women of 49 years in THIN. reproductive age.16 Most women presenting with symptoms of androgen excess have PCOS,17 which is METHODS also associated with alopecia, menstrual disturbances Study population and anovulation.18 We therefore searched for Read THIN contains anonymised patient data recorded by codes suggestive of: (1) acne, including specific treat- general practitioners (GPs) in 578 participating ments such as tetracycline agents, macrolides, isotreti- primary care practices and includes approximately 6% noin and topical treatments; (2) hirsutism; (3) PCOS; of the UK population.14 In THIN, diagnoses are (4) oligomenorrhoea; (5) anovulation/infertility; (6) recorded using Read codes, and GPs can provide alopecia; and (7) gynaecological disorders. This final further information as free-text entries.15 To date, group included conditions such as dysmenorrhoea, more than 380 research articles have been published menorrhagia, irregular menstruation, premenstrual 248 Cea-Soriano L, et al.