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RESEARCH: Bette Liu, Valerie Beral, Angela Balkwill, Jane Green, Siân Sweetland, Gillian Reeves for the Million Women Study Collaborators Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study BMJ 2008; 337: a386 [Abstract] [Full text]

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Is the transdermal patch a possible way forward for postmenopausal women requiring HRT?

Savio G Barreto, Merlyn Barreto, Savio G. Barreto, Parul J. Shukla   (21 July 2008)

Research priorities of the Million Women Study (MWS)

C Guenther   (31 July 2008)

Is the transdermal patch a possible way forward for postmenopausal women requiring HRT? 21 July 2008
Savio G Barreto, Registrar Department of General & Digestive Surgery, Flinder Medical Centre, Adelaide, SA 5042, Australia, Merlyn Barreto, Savio G. Barreto, Parul J. Shukla Send response to journal: Re: Is the transdermal patch a possible way forward for postmenopausal women requiring HRT?	We read with interest the article by Liu et al.1 comparing transdermal and oral hormone replacement therapy (HRT) in gallstone disease. The benefit of HRT in ameliorating vasomotor and urogenital symptoms of menopause and menopause-related osteoporosis cannot be undermined. However, numerous studies have indicated that besides the adverse cardiovascular side-effects following oral administration of oestrogens,2 the possibility of developing gallstone disease was real. 3,4 This obviously led to considerable uncertainty in the minds of users and prescribers of HRT resulting in narrowing down the indications for HRT use in postmenopausal women. While this study has confirmed the existence of ‘the problem’ of the adverse effect of oestrogen-containing HRT on gallstone disease it has also provided in part - a ‘solution’. The lowered risk of gallstone disease in postmenopausal women using transdermal patches based on the outcomes of this large-scale cohort study proves a shot in the arm for prescribers of transdermal patches. By highlighting the beneficial effect of transdermal patches on reducing the rate of cholecystectomies, the authors have indirectly steered clear of the criticism against previous studies that failed to differentiate the impact of oestrogen-containing HRT on symptomatic gallstones and the rate of conversion of asymptomatic to symptomatic gallstones. The influence of oestrogen dose on gallstone formation (higher doses associated with higher risk) was also shown. The high incidence of gallstones in patients with implants seems to cast serious doubts on first pass metabolism as causative for gallstones. While we do believe that the development of gallstone disease is just one side effect of HRT, this study does provide further evidence to support the use of transdermal patches in the management algorithm of women requiring oestrogen replacement therapy. References 1) Liu B, Beral V, Balkwill A, Green J, Sweetland S, Reeves G and for the Million Women Study Collaborators. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ 2008;337:a386. 2) Rossouw JE, Anderson GL, Prentice RL, La-Croix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–33. 3) Simon JA, Hunninghake DB, Agarwal SK, Lin F, Cauley JA, Ireland CC, Pickar JH: Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease: the Heart and Estrogen/Progestin Replacement Study. Ann Intern Med 2001;135:493–501. 4) Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, Larson JC: Effect of estrogen therapy on gallbladder disease. JAMA 2005;293:330–9. Competing interests: None declared
Research priorities of the Million Women Study (MWS) 31 July 2008
C Guenther, Dr. Kade/Besins 12277 Berlin, Germany Send response to journal: Re: Research priorities of the Million Women Study (MWS)	The article of Liu and MWS Collaborators confirms a higher risk of gallbladder disease and cholecystectomies in association with hormone replacement therapy (HRT), as already reported from the Nurses' Health Study, HERS and the WHI. The authors' calculations of absolute differences in risk reveals that one extra case of cholecystectomy in 500 users of transdermal HRT has to be expected over 5 years in comparison to one extra case in 111 users of oral HRT over 5 years. It seems that the risk of gallbladder disease with HRT is of secondary importance and may well be balanced by HRT benefits. Prior MWS analyses focused on breast, endometrial and ovarian cancer at the risk lever of the balance as well as on fractures at the benefit lever. In each of their publications on risks the MWS collaborators carved out absolute differences and extrapolations to the population level. However, given the ubiquitous effects of HRT, to get the right perspective and the true net impact it is necessary to investigate the most relevant issues for the health of peri- and postmenopausal women, i.e. overall, total cancer-related and cardiovascular mortality as well as cardiovascular and total cancer morbidity. From the publication of Liu et al. (cf. table 1) it seems, that the information to analyze these topics is available. Before exploring secondary effects it is necessary to show the objective data of primary importance. Competing interests: Employee of a pharmaceutical company selling HRT products