Figure 1Flow chart of participant selection. HIRA, Korean Health Insurance Review and Assessment Service; LT3, liothyronine; LT4, levothyroxine; PDC, proportion of days covered.
Table 1.Baseline characteristics of the cohort participants who were prescribed levothyroxine monotherapy among a population of elderly women with hypothyroidism, according to the daily levothyroxine dose
Characteristics |
Total (%) |
Daily levothyroxine dose (%)
|
p-value |
≤ 50 μg/d |
51-100 μg/d |
101-150 μg/d |
> 150 μg/d |
Age (mean±SD) |
70.7±5.0 |
71.3±5.3 |
70.7±5.0 |
70.2±4.6 |
70.5±4.9 |
<0.01 |
65-69 |
5510 (49.4) |
1029 (44.8) |
3037 (49.8) |
884 (52.8) |
560 (51.5) |
|
70-74 |
3213 (28.8) |
676 (29.4) |
1737 (28.5) |
494 (29.5) |
306 (28.1) |
|
75-79 |
1726 (15.5) |
404 (17.6) |
945 (15.5) |
224 (13.4) |
153 (14.1) |
|
≥80 |
706 (6.3) |
187 (8.1) |
378 (6.2) |
72 (4.3) |
69 (6.3) |
|
Comorbidity |
|
|
|
|
|
|
Osteoporosis |
3976 (35.6) |
801 (34.9) |
2167 (35.5) |
624 (37.3) |
384 (35.3) |
0.46 |
Malignancy |
639 (5.7) |
112 (4.9) |
355 (5.8) |
92 (5.5) |
80 (7.4) |
0.03 |
Diabetes mellitus |
4364 (39.1) |
933 (40.6) |
2370 (38.9) |
663 (39.6) |
398 (36.6) |
0.14 |
Hypoparathyroidism |
116 (1.0) |
15 (0.7) |
52 (0.9) |
23 (1.4) |
26 (2.4) |
<0.01 |
Cushing syndrome |
47 (0.4) |
3 (0.1) |
33 (0.5) |
8 (0.5) |
3 (0.3) |
0.06 |
Adrenal disorder |
68 (0.6) |
15 (1.6) |
40 (0.7) |
10 (0.6) |
3 (0.3) |
0.51 |
COPD |
2010 (18.0) |
401 (17.5) |
1090 (17.9) |
295 (17.6) |
224 (20.6) |
0.13 |
Asthma |
2738 (24.6) |
577 (25.1) |
1470 (24.1) |
396 (23.7) |
295 (27.1) |
0.13 |
Chronic liver disease |
2098 (18.8) |
420 (18.3) |
1187 (19.5) |
292 (17.4) |
199 (18.3) |
0.22 |
Chronic kidney disease |
280 (2.5) |
78 (3.4) |
133 (2.2) |
40 (2.4) |
29 (2.7) |
0.02 |
Heart failure |
868 (7.8) |
235 (10.2) |
427 (7.0) |
122 (7.3) |
84 (7.7) |
<0.01 |
Ischemic heart disease |
2547 (22.8) |
595 (24.2) |
1353 (22.2) |
371 (22.2) |
228 (21.0) |
<0.01 |
Arrhythmia |
906 (8.1) |
250 (11.1) |
472 (7.7) |
100 (6.0) |
84 (7.7) |
<0.01 |
Dementia |
325 (2.9) |
95 (4.1) |
165 (2.7) |
42 (2.5) |
23 (2.1) |
<0.01 |
Stroke |
1256 (11.3) |
297 (12.9) |
688 (11.3) |
153 (9.1) |
118 (10.9) |
<0.01 |
Epilepsy |
239 (2.1) |
62 (2.7) |
122 (2.0) |
32 (1.9) |
23 (2.1) |
0.22 |
Charlson comorbidity score (mean±SD) |
2.23±1.94 |
2.40±1.93 |
2.17±1.90 |
2.18±2.01 |
2.29±2.03 |
<0.01 |
0 |
1952 (17.5) |
348 (15.2) |
1092 (17.9) |
318 (19.0) |
194 (17.8) |
|
1 |
2722 (24.4) |
496 (21.6) |
1566 (25.7) |
412 (24.6) |
248 (22.8) |
|
2 |
2388 (21.4) |
508 (22.1) |
1277 (20.9) |
353 (21.1) |
250 (23.0) |
|
3 |
1756 (15.7) |
391 (17.0) |
951 (15.6) |
262 (15.7) |
152 (14.0) |
|
≥4 |
2337 (21.0) |
553 (24.1) |
1211 (19.6) |
329 (19.7) |
244 (22.4) |
|
Co-medication |
|
|
|
|
|
|
Glucocorticoid |
6614 (59.3) |
1344 (58.5) |
3551 (58.2) |
1028 (61.4) |
691 (63.5) |
<0.01 |
Anti-coagulants |
266 (2.4) |
76 (3.3) |
128 (2.1) |
40 (2.4) |
22 (2.0) |
0.01 |
Anti-epileptics |
1520 (13.6) |
325 (14.2) |
803 (13.2) |
215 (12.8) |
177 (16.3) |
0.03 |
Anti-depressants |
2446 (21.9) |
538 (23.4) |
1314 (21.6) |
342 (20.4) |
252 (23.2) |
0.08 |
Benzodiazepines |
7327 (65.7) |
1521 (66.3) |
3992 (65.5) |
1090 (65.1) |
724 (66.5) |
0.79 |
Proton pump inhibitor |
1153 (10.3) |
266 (11.6) |
604 (9.9) |
159 (9.5) |
124 (11.4) |
0.05 |
Thiazolidinedion |
371 (3.3) |
89 (3.9) |
190 (3.1) |
54 (3.2) |
38 (3.5) |
0.37 |
Raloxifene |
351 (3.2) |
76 (3.3) |
202 (3.3) |
50 (3.0) |
23 (2.1) |
0.19 |
Bisphosphonate |
2089 (18.7) |
436 (19.0) |
1151 (18.9) |
320 (19.1) |
182 (16.7) |
0.36 |
No. of health service use (mean±SD) |
34.0±17.0 |
34.3±16.9 |
33.7±16.9 |
33.7±16.9 |
35.2±18.0 |
<0.01 |
1-19 |
2119 (19.0) |
415 (18.1) |
1167 (19.1) |
325 (19.4) |
212 (19.5) |
|
20-39 |
5564 (49.9) |
1156 (50.4) |
3066 (50.3) |
835 (49.9) |
507 (46.6) |
|
40-59 |
2585 (23.2) |
550 (24.0) |
1392 (22.8) |
379 (22.6) |
264 (24.3) |
|
≥60 |
887 (8.0) |
175 (7.6) |
472 (7.7) |
135 (8.1) |
105 (9.7) |
|
Total |
11 155 (100.0) |
2296 (100.0) |
6097 (100.0) |
1674 (100.0) |
1088 (100.0) |
|
Table 2.Baseline characteristics of subgroup participants who were prescribed levothyroxine monotherapy among a population of elderly women with hypothyroidism, according to the osteoporosis status
Characteristics |
Highly probable osteoporosis (%)1
|
Probable osteoporosis (%)2
|
Non-osteoporosis (%)3
|
p-value |
Daily levothyroxine dose (mean±SD, μg/d) |
98.2±42.2 |
101.6±44.5 |
99.0±43.5 |
0.02 |
≤50 |
453 (21.0) |
468 (19.2) |
1375 (21.0) |
|
51-100 |
1193 (55.3) |
1306 (53.6) |
3598 (54.8) |
|
101-150 |
328 (15.2) |
404 (16.6) |
942 (14.4) |
|
>150 |
183 (8.5) |
259 (10.6) |
646 (9.9) |
|
Age (mean±SD) |
71.0±4.9 |
70.1±4.6 |
70.8±5.2 |
<0.01 |
65-69 |
987 (45.8) |
1306 (53.6) |
3217 (49.0) |
|
70-74 |
676 (31.3) |
699 (28.7) |
1838 (28.0) |
|
75-79 |
360 (16.7) |
331 (13.6) |
1035 (15.8) |
|
≥80 |
134 (6.2) |
101 (4.1) |
471 (7.2) |
|
Comorbidity |
|
|
|
|
Malignancy |
140 (6.5) |
138 (5.7) |
361 (5.5) |
0.23 |
Diabetes Mellitus |
829 (38.4) |
965 (39.6) |
2570 (39.2) |
0.72 |
Hypoparathyroidism |
24 (1.1) |
60 (2.5) |
32 (0.5) |
<0.01 |
Cushing syndrome |
20 (0.9) |
7 (0.3) |
20 (0.3) |
<0.01 |
Adrenal disorder |
30 (1.4) |
10 (0.4) |
28 (0.4) |
<0.01 |
COPD |
444 (20.6) |
479 (19.7) |
1087 (16.6) |
<0.01 |
Asthma |
591 (27.4) |
659 (27.0) |
1488 (22.7) |
<0.01 |
Chronic liver disease |
402 (18.6) |
527 (21.6) |
1169 (17.8) |
<0.01 |
Chronic kidney disease |
32 (1.5) |
41 (1.7) |
207 (3.2) |
<0.01 |
Heart failure |
150 (7.0) |
168 (6.9) |
550 (8.4) |
0.02 |
Ischemic heart disease |
508 (23.6) |
566 (23.3) |
1473 (22.5) |
0.50 |
Arrhythmia |
174 (8.1) |
175 (7.2) |
557 (8.5) |
0.13 |
Dementia |
77 (3.6) |
64 (2.6) |
184 (2.8) |
0.12 |
Stroke |
263 (12.2) |
277 (11.4) |
716 (10.9) |
0.26 |
Epilepsy |
54 (2.5) |
51 (2.1) |
134 (2.0) |
0.43 |
Charlson comorbidity score (mean±SD) |
2.41±1.95 |
2.31±1.91 |
2.14±1.94 |
<0.01 |
0 |
333 (15.4) |
383 (15.7) |
1236 (18.8) |
|
1 |
454 (21.1) |
556 (22.8) |
1712 (26.1) |
|
2 |
462 (21.4) |
550 (22.6) |
1376 (21.0) |
|
3 |
398 (18.5) |
413 (17.0) |
945 (14.4) |
|
≥4 |
510 (23.6) |
535 (22.0) |
1292 (19.7) |
|
Co-medication |
|
|
|
|
Glucocorticoid |
1462 (67.8) |
1593 (65.4) |
3559 (54.2) |
<0.01 |
Anti-coagulants |
47 (2.2) |
49 (2.0) |
170 (2.6) |
0.22 |
Anti-epileptics |
408 (18.9) |
347 (14.2) |
7665 (11.7) |
<0.01 |
Anti-depressants |
546 (25.3) |
563 (23.1) |
1337 (20.4) |
<0.01 |
Benzodiazepines |
1538 (71.3) |
1675 (68.7) |
4114 (62.7) |
<0.01 |
Proton pump inhibitor |
279 (12.9) |
299 (12.3) |
575 (8.8) |
<0.01 |
Thiazolidinedion |
69 (3.2) |
73 (3.0) |
229 (3.5) |
0.48 |
No of health service use (mean±SD) |
38.8±18.7 |
37.8±17.8 |
30.9±15.4 |
<0.01 |
1-19 |
270 (12.5) |
318 (13.1) |
1531 (23.3) |
|
20-39 |
965 (44.7) |
1150 (47.2) |
3449 (52.6) |
|
40-59 |
640 (29.7) |
680 (27.9) |
1265 (19.3) |
|
≥60 |
282 (13.1) |
289 (11.9) |
316 (4.8) |
|
Total |
2157 (100.0) |
2437 (100.0) |
6561 (100.0) |
|
Table 3.Association between the daily levothyroxine dose and the fracture risk, according to the osteoporosis status in elderly women with hypothyroidism
Daily levothyroxine dose (μg/d) |
No. of participants (%) |
No. of events |
Incidence rate (/1,000 PY) |
cHR (95% CI) |
aHR1 (95% CI) |
Osteoporosis2
|
|
|
|
|
|
≤50 |
921 (20.1) |
46 |
42.4 |
1.22 (0.86, 1.75) |
1.16 (0.80, 1.66) |
51-100 |
2499 (54.4) |
115 |
36.0 |
Reference |
Reference |
101-150 |
732 (15.9) |
37 |
37.9 |
1.09 (0.75, 1.58) |
1.16 (0.80, 1.69) |
>150 |
442 (9.6) |
29 |
50.7 |
1.49 (0.99, 2.24) |
1.56 (1.03, 2.37) |
|
4594 (100.0) |
227 |
39.0 |
|
|
Highly probable osteoporosis3
|
|
|
|
|
|
≤50 |
453 (21.0) |
22 |
41.9 |
0.97 (0.60, 1.57) |
0.93 (0.55, 1.56) |
51-100 |
1193 (55.3) |
67 |
44.3 |
Reference |
Reference |
101-150 |
328 (15.2) |
18 |
41.1 |
0.91 (0.54, 1.54) |
0.92 (0.54, 1.58) |
>150 |
183 (8.5) |
19 |
81.9 |
1.85 (1.11, 3.07) |
1.93 (1.14, 3.26) |
|
2157 (100.0) |
126 |
46.5 |
|
|
Probable osteoporosis4
|
|
|
|
|
|
≤50 |
468 (19.2) |
24 |
42.9 |
1.52 (0.93, 2.48) |
1.43 (0.84, 2.42) |
51-100 |
1306 (53.6) |
48 |
28.6 |
Reference |
Reference |
101-150 |
404 (16.6) |
19 |
35.3 |
1.23 (0.72, 2.09) |
1.60 (0.90, 2.82) |
>150 |
259 (10.6) |
10 |
29.4 |
1.03 (0.52, 2.03) |
1.25 (0.62, 2.55) |
|
2437 (100.0) |
101 |
32.4 |
|
|
Non-osteoporosis5
|
|
|
|
|
|
≤50 |
1375 (21.0) |
52 |
31.7 |
1.07 (0.78, 1.47) |
1.05 (0.75, 1.47) |
51-100 |
3598 (54.8) |
138 |
29.9 |
Reference |
Reference |
101-150 |
942 (14.4) |
44 |
35.4 |
1.18 (0.84, 1.66) |
1.10 (0.78, 1.56) |
>150 |
646 (9.9) |
22 |
26.2 |
0.88 (0.56, 1.37) |
0.84 (0.52, 1.35) |
|
6561 (100.0) |
256 |
30.7 |
|
|
All elderly women in our dataset |
|
|
|
|
|
|
2 533 289 |
175 783 |
46.3 |
|
|