Simonsen et al. Estrogen Therapy and Risk of Gallstone Disease

Supplementary Materiel

Table 1. International Classification of Diseases Codes used in the Analysis.

Hospital discharge codes
Alcoholism
ICD-10: F10 (except F10.0), G31.2, G62.1, G72.1, I42.6, K29.2, K86.0, Z72.1
ICD-8: 291, 303, 577.10, 571.09, 571.10
and/or a prescription of disulfiram (ATC N07BB01)
Apoplexia cerebri
ICD-10: I61, I63, I64
ICD-8: 431, 433, 434
Chronic obstructive pulmonary disease
ICD-10: J41, J42, J43, J44
ICD-8: 491, 492
Cancer
ICD-10: C0–C97 (except C22–25)
ICD-8: 14–20 (except 155, 156, 157)
Cardiac disease
ICD-10: I05–I09, I10–I15, I20–I25, I50
ICD-8: 393–398, 400–404, 410–414, 427.09, 427.10, 427.19
Diabetes
ICD-10: E10.0, E10.1–E10.9, E11.0; E11.1–E11.9
ICD-8: 249.00, 249.01– 249.09, 250.00, 250.01–250.09
Gallstone disease (including cholecystitis)
ICD-10: K80-K81
ICD-8: 574-575
Hypothyroidism
ICD-10: E00–E03
ICD-8: 244
Hyperlipidemia
ICD-10: E78.0–E78.5
ICD-10: 272.00, 272.01, 279.00, 279.01
Inflammatory Bowel Disease
ICD-10: K50, K51
ICD-8: 563.01, 563.19
Liver cirrhosis
ICD-10: K70.3, K74.6
ICD-8: 571.09, 571.92, 571.99
Liver, bile duct and pancreatic cancer
ICD-10: C22-C25
ICD-8: 155-157
Obesity
ICD-10: E66
ICD-8: 277
Renal failure
ICD-10: N17–N19
ICD-8: 581–584
Transient ischemic attack
ICD-10: G45.9
ICD-8: 435
Abbreviations: ICD-8, International Classification of Diseases, Eighth Revision; ICD-10, International Classification of Diseases, Tenth Revision.

Table 2. Procedure Codes used in the Analysis.

Gallbladder surgery
After 1996
KJKA including cholecystectomy and drainage
Before 1996
47360, 47365
Hysterectomy
After 1996
KLCD00-97
Before 1996
60920, 60940

Table 3. Anatomical Therapeutic Chemical Classification System Codes used in the Analysis

Hormone replacement therapy
Estrogens
G03CA01, G03CA03, G03CA04, G03CA57, G03CB03
Estrogen + progesterone in combination
G03CX01, G03DC05, G03FA01, G03FA12, G03FA17, G03FB05, G03FB06, G03FB11.
Progesterones
G03DA02, L02AB02.
Other drugs (covariates)
Statins: C10AA
Other lipid-lowering drugs: C10AB, C10AD, C10AC
Thiazide: CO3AA
Antidiabetics: A10

Table 4. Use of Estrogens and the Risk of Gallstone Disease. Stratified according to intensity of treatment. Northern Denmark, 1996-2010.

Estrogen Use / Cases With Gallstone Disease / Population Controlsa / Crude OR / 95% CI / Adjusted ORb / 95% CI
No. / % / No. / %
None / 12,853 / 78.4 / 138,131 / 84.3 / 1.0 / Reference / 1.0 / Reference
User / 3,533 / 21.6 / 25,729 / 15.7 / 1.52 / 1.46, 1.58 / 1.48 / 1.42, 1.55
Current use
Overall
2-4 prescrip-tions
5-19 prescrip-tions
≥ 20 prescrip-tions / 1,425
82
588
755 / 8.7
0.5
3.6
4.6 / 8,930
554
3,625
4,751 / 5.4
0.3
2.2
2.9 / 1.76
1.62
1.80
1.76 / 1.66, 1.87
1.28, 2.05
1.64, 1.97
1.62, 1.90 / 1.74
1.60
1.78
1.72 / 1.64, 1.85
1.26, 2.02
1.63, 1.95
1.59, 1.87
Former use
Overall
2-4 prescrip-tions
5-19 prescrip-tions
≥ 20 prescrip-tions / 2,108
445
923
740 / 12.9
2.7
5.6
4.5 / 16,799
3,716
7,109
5,974 / 10.3
2.3
4.3
3.6 / 1,38
1.31
1.43
1.36 / 1.31, 1.45
1.19, 1.45
1.33, 1.54
1.26, 1.48 / 1.35
1.27
1.41
1.33 / 1.28, 1.42
1.15, 1,41
1.31, 1.51
1.22, 1.44

Abbreviations: CI, confidence interval; OR, odds ratio.

a Matched by age, sex and county.

b Adjusted for the previous hospital discharge diagnoses and treatments mentioned in Table 1, parity and period of diagnosis. Matched by age, sex and county.

Table 5. Use of Estrogens and the Risk of Gallstone Disease. Stratified according to index date. Northern Denmark, 1996-2010.

Estrogen Use / Cases With Gallstone Disease / Population Controls / Crude ORa / 95% CI / Adjusted ORb / 95% CI
No. / % / No. / %
All
Overall
Current use
Former use / 3,533
1,425
2,108 / 21.6
8.7
12.9 / 25,729
8,930
16,999 / 15.7
5.4
10.3 / 1.52
1.76
1.38 / 1.46-1.58
1.66-1.87
1.31-1.45 / 1.48
1.74
1.35 / 1.42-1.55
1.64-1.85
1.28-1.42
Index date ≤ 2002
Overall
Current use
Former use / 1,281
759
522-1.42s are shown in the table below.which cases/controls have been divided in to strata XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX / 21.3
12.6
8.7 / 8,584
4,769
3,815 / 14.3
7.9
6.3 / 1.68
1.80
1.54 / 1.57-1.80
1.65-1.96
1.40-1.70 / 1.67
1.79
1.52 / 1.56-1.79
1.65-1.95
1.37-1.67
Index date > 2002
Overall
Current use
Former use / 2,252
666
1,586 / 21.7
6.4
15.3 / 17,145
4,161
12,984 / 16.5
4.0
12.5 / 1.43
1.74
1.33 / 1.36-1.51
1.60-1.90
1.25-1.41 / 1.39
1.69
1.29 / 1.32-1.47
1.55-1.85
1.22-1.37

Abbreviations: CI, confidence interval; OR, odds ratio.

a Matched by age, sex and county.

b Adjusted for the previous hospital discharge diagnoses and treatments mentioned in Table 1, parity and period of diagnosis. Matched by age, sex and county.

Table 6. Use of Estrogens and the Risk of Gallstone Disease. Cut-off 30, 90 and 180 days. Northern Denmark, 1996-2010.

Estrogen Use / Cases With Gallstone Disease / Population Controlsa / Crude OR / 95% CI / Adjusted ORb / 95% CI
No. / % / No. / %
None / 12,853 / 78.4 / 138,131 / 84.3 / 1.0 / Reference / 1.0 / Reference
User / 3,533 / 21.6 / 25,729 / 15.7 / 1.52 / 1.46, 1.58 / 1.48 / 1.42, 1.55
Cut-off 90 days
Current use
Former use / 1,425
2,108 / 8.7
12.9 / 8,930
16,799 / 5.4
10.3 / 1.76
1.38 / 1.66, 1.87
1.31, 1.45 / 1.74
1.35 / 1.64, 1.85
1.28, 1.42
Cut-off 30 days
Current use
Former use / 530
3,003 / 3.2
18.3 / 3,394
22,335 / 2.1
13.6 / 1.72
1.48 / 1.57, 1.89
1.42, 1.55 / 1.70
1.45 / 1.54, 1.86
1.39, 1.52
Cut-off 180 days
Current use
Former use / 1,716
1,817 / 10.5
11.1 / 10,804
14,925 / 6.6
9.1 / 1,76
1.34 / 1.66, 1.86
1.27, 1.41 / 1.73
1.30 / 1.64, 1.83
1.24, 1.38

Abbreviations: CI, confidence interval; OR, odds ratio.

a Matched by age, sex and county.

b Adjusted for the previous hospital discharge diagnoses and treatments mentioned in Table 1, parity and period of diagnosis. Matched by age, sex and county.

Table 7. Use of Estrogens and the Risk of Gallstone Disease. Cases/controls with only 1 redeemed prescription have been excluded. Northern Denmark, 1996-2010.

Estrogen Use / Cases With Gallstone Disease / Population Controls / Crude ORa / 95% CI / Adjusted ORb / 95% CI
No. / % / No. / %
None / 12,364 / 77.8 / 134,539 / 83.9 / 1.0 / Reference / 1.0 / Reference
User / 3,533 / 22.2 / 25,729 / 16.1 / 1.54 / 1.48, 1.61 / 1.51 / 1.45, 1.57
Current use / 1,425 / 9.0 / 8,930 / 5.6 / 1.80 / 1.69, 1.91 / 1.77 / 1.66, 1.88
Former use / 2,108 / 13.3 / 16,799 / 10.5 / 1.40 / 1.34, 1.48 / 1.37 / 1.30, 1.44

Abbreviations: CI, confidence interval; OR, odds ratio.

a Matched by age, sex and county.

b Adjusted for the previous hospital discharge diagnoses and treatments mentioned in Table 1, parity and period of diagnosis. Matched by age, sex and county.

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