Hormone Replacement Therapy and the Risk of Melanoma in Post-menopausal Women

CCI = Charlson Comorbidity Index; COPD = chronic obstructive pulmonary disease; DDD = defined daily dose; HRT = hormone replacement therapy; IQR = interquartile range; NSAID = non-steroidal anti-inflammatory drug.
^aHigh PPI HRT use considered filled prescriptions equivalent to ≥1000 DDDs.
^bHaving filled ≥2 prescriptions more than 2 years prior to the index date.

CI = confidence interval; OR = odds ratio.
^aHRT modelled as high use, corresponding to ≥1000 DDDs.
^bRecent high use defined as a cumulative dose of ≥1000 DDDs amongst users with a filled prescription in the 2 years prior to index date.
^cAdjusted for age and calendar time (by risk-set matching and the conditional analysis).
^dAdjusted for drugs suggested to have photosensitizing properties, oral contraceptive use, low-dose aspirin, NSAIDs, statins, diabetes, COPD, chronic renal insufficiency, diseases associated with heavy alcohol consumption, inflammatory bowel disease, psoriasis, sarcoidosis and stroke, modified Charlson Comorbidity Index (CCI) score (0 low; 1–2 medium; ≥3 high) and highest achieved education (basic, medium, higher or unknown).

^aHigh use (≥1000 DDDs).
^bAdjusted for age and calendar time (by risk-set matching and the conditional analysis).
^cAdjusted for drugs suggested to have photosensitizing properties, oral contraceptive use, low-dose aspirin, NSAIDs, statins, diabetes, COPD, chronic renal insufficiency, diseases associated with heavy alcohol consumption, inflammatory bowel disease, psoriasis, sarcoidosis and stroke, CCI score (0 low; 1–2 medium; ≥3 high) and highest achieved education (basic, medium, higher or unknown).
^dDerived from a likelihood ratio test of the conditional logistic regression model without interaction terms nested in a conditional logistic regression model with interaction terms.
^eLocalised disease includes stage I or II melanoma (depending on thickness of the tumour), non-localised disease includes cases with dissemination (either regionally stage III, or widespread stage IV).

HR = hazard ratio.
^aPer 1000 person-years.
^bAdjusted for drugs suggested to have photosensitizing properties, oral contraceptive use, low-dose aspirin, NSAIDs, statins, diabetes, COPD, chronic renal insufficiency, diseases associated with heavy alcohol consumption, inflammatory bowel disease, psoriasis, sarcoidosis and stroke, CCI score (0 low; 1–2 medium; ≥3 high) and highest achieved education (basic, medium, higher or unknown).
^cAdditionally adjusting for stage.

^aPer 1000 person-years.
^bAdjusted for drugs suggested to have photosensitizing properties, oral contraceptive use, low-dose aspirin, NSAIDs, statins, diabetes, COPD, chronic renal insufficiency, diseases associated with heavy alcohol consumption, inflammatory bowel disease, psoriasis, sarcoidosis and stroke, CCI score (0 low; 1–2 medium; ≥3 high) and highest achieved education (basic, medium, higher or unknown).
^cAdditionally adjusting for stage.

Authors and Disclosures

B.M. Hicks^1,*, K.B. Kristensen², S.A. Pedersen³, L.R. Hölmich⁴ and A. Pottegård<sup>2

1</sup>Centre for Public Health, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, Northern Ireland ²Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark ³Department of Clinical Biochemistry and Clinical Pharmacology, Odense University Hospital, Odense, Denmark ⁴Department of Plastic Surgery, Herlev and Gentofte Hospital, Herlev, Denmark

*Correspondence address
Centre for Public Health, ICSB, Royal Victoria Hospital, Belfast, N. Ireland, BT12 6BA. Tel: +44-0-28-90-63-50-09; E-mail: B.Hicks@qub.ac.uk

Authors' roles
All authors conceived and designed the study, analysed and interpreted the data and critically revised the article for important intellectual content. A.P. acquired the data. K.B.K. analysed the data. B.M.H. wrote the article, and all authors participated in the interpretation of the results and critical revision of the article.

Conflicts of interest
A.P. reports participation in research projects funded by Alcon, Almirall, Astellas, Astra-Zeneca, Boehringer-Ingelheim, Servier, Novo Nordisk and LEO Pharma, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this article. The other authors have no competing interests to declare.