Conflicting studies exist on the association between menopausal hormone therapy (MHT) and skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This retrospective cohort study aimed to evaluate the risk of skin cancer from MHT using data from 2002 to 2019 from the National Health Insurance Service in South Korea. We included 192,202 patients with MHT and 494,343 healthy controls. Women > 40 years who had menopause between 2002 and 2011 were included. Patients with MHT had at least one MHT for at least 6 months and healthy controls had never been prescribed MHT agents. We measured the incidence of melanoma and NMSC. Melanoma developed in 70 (0.03%) patients with MHT and 249 (0.05%) controls, while the incidence of NMSC was 417 (0.22%) in the MHT group and 1680 (0.34%) in the controls. Tibolone (hazard ratio [HR] 0.812, 95% confidence interval [CI] 0.694–0.949) and combined oestrogen plus progestin by the manufacturer (COPM; HR 0.777, 95% CI 0.63–0.962) lowered the risk of NMSC, while other hormone groups did not change the risk. Overall, MHT was not associated with melanoma incidence in menopausal Korean women. Instead, tibolone and COPM were associated with a decrease in NMSC occurrence.
Hormones can affect the development of skin tumors, and this is supported by reports of changes in nevi and melanoma during pregnancy, such as their enlargement and darkening. Melanocytes are known to respond to oestrogen stimulation, and in vitro studies have found that skin treated with oestrogen can express up to three times the amount of melanin[
This retrospective cohort study used data from the National Health Insurance Service (NHIS) from 01 January 2002 to 31 December 2019. Around 98% of the population is eligible to receive healthcare coverage under the NHIS in South Korea[
The NHIS covers national screening, including cardiovascular examinations, for all employees, insured individuals aged 40 or more every other year, and for blue-collar employees every year[
Diagnoses were recorded in the database using the International Classification of Diseases, 10th revision (ICD-10). Surgeries and procedures were recorded using the Korea Health Insurance Medical Care Expenses (2012, 2016, 2019 version).
Women over the age of 40 who had menopause between 2002 and 2011 were selected as cases and controls. The MHT group included women who had used at least one MHT for at least 6 months between 2002 and 2011, whereas the non-MHT group included those who had never been prescribed MHT agents between 2002 and 2019.
We excluded the following patients from both groups: (
Melanoma and NMSC were defined as ICD-10 codes C43 and C44, respectively. Melanoma was defined as three or more visits to hospitals with a diagnosis code of C43. NMSC was defined as three or more visits with a diagnosis code of C44. In the case of more than one cancer, it was defined as a total skin cancer.
The MHT agents investigated in this study were limited to tibolone, combined oestrogen and progestin by the manufacturer (COPM), oestrogen, combined oestrogen and progestin by the physician (COPP), and topical oestrogen. A detailed list of the medications is provided in Supplementary Table S1. If two or more MHT agents were used sequentially, they were assigned to the last MHT group used for > 6 months.
Age, body mass index (BMI), socioeconomic status (SES), region, Charlson Comorbidity Index (CCI), parity, age at menarche, age at menopause, smoking, alcohol consumption, physical exercise, and the period from menopause to inclusion were investigated. The reference date was the registration date of the participants in this study. Obesity was defined by the Asia–Pacific classification[
All statistical tests were two-sided, and p-values less than 0.05 were considered statistically significant. Continuous variables are expressed as median [25th–75th percentile], and categorical variables are expressed as numbers or percentages. To evaluate the association between MHT use and skin cancer risk, we used the Cox proportional hazards model. To ensure the robustness of this study, only cases prescribed by obstetricians or gynaecologists were analysed for the MHT group. We used the pairwise deletion method to handle missing values. The start date of the MHT group was defined as the date on which the first MHT was prescribed, whereas that of the control group was defined as the day on which the national health and cancer check-up was performed. If only the examination year was recorded, June 30 of the health examination year was defined as the starting date. In the absence of special events, the last day of the study was set as the date of death or 31 December 2019. All statistical analyses were conducted using the SAS Enterprise Guide 6.1 (SAS Institute, Cary, NC, USA).
This study was approved by the institutional review board of Inje University Sanggye Paik Hospital (SGPAIK-2020-08-002). We were able to export only the de-identified data relevant to the study from the virtual server within the NHIS using the NHIS privacy policy. The requirement for informed consent from the study subjects was waived by the institutional review board of Inje University Sanggye Paik Hospital because study would not affect rights and welfare of subject and could not be practicably carried out without the waiver. This study was conducted in accordance with the principles of the Declaration of Helsinki.
Among the 2,506,271 women who reported menopause during the medical examination from 2002 to 2011, 192,202 women were included in the MHT group, and 494,343 women were included in the non-MHT group (Fig. 1). The average age of the participants was 56 [52–62] years old. Table 1 and Supplementary Table S2 show the detailed characteristics of the participants in this study. The average duration of hormone therapy was 22 [10–54] months (Table 2).
Graph: Figure 1Flowchart to select case–control according to MHT in Korea National Health Insurance Data (2002–2019). MHT Menopausal hormone therapy.
Table 1 Characteristics of women according to menopausal hormone exposure status at recruitment, Korea National Health Insurance Data, from 2002 to 2019.
Non-MHT Tibolone CEPM Oral estrogen CEPP Topical estrogen Total Number of women 494,343 97,074 60,776 29,478 3686 1188 686,545 Median age (years) 58 [52–64] 54 [50–58] 52 [50–56] 52 [49–57] 54 [51–59] 53 [50–57] 56 [52–62] Age at inclusion (years) 40–49 48,869 (9.9) 17,283 (17.8) 14,132 (23.3) 7882 (26.7) 665 (18) 265 (22.3) 89,096 (13) 50–59 236,883 (47.9) 62,392 (64.3) 39,636 (65.2) 16,151 (54.8) 2156 (58.5) 715 (60.2) 357,933 (52.1) 60–69 150,340 (34.5) 15,583 (16.4) 6457 (10.7) 4524 (15.8) 756 (21.1) 186 (16) 177,846 (28.5) ≥ 70 58,251 (11.8) 1816 (1.9) 551 (0.9) 921 (3.1) 109 (3) 22 (1.9) 61,670 (9) Median BMI (kg/m2) 23.9 [22.1–26] 23.5 [21.8–25.4] 23.2 [21.5–25.1] 23.8 [22–25.8] 23.4 [21.6–25.2] 23.8 [22.1–25.7] 23.8 [21.9–25.8] BMI (kg/m2) < 18.5 9560 (2) 1726 (1.8) 1229 (2) 451 (1.5) 74 (2) 22 (1.9) 13,062 (1.9) 18.5–22.9 167,506 (34.7) 38,181 (39.8) 26,883 (44.6) 10,628 (36.4) 1528 (41.9) 436 (37) 245,162 (36.4) 23–24.9 127,678 (26.4) 26,754 (27.9) 16,224 (26.9) 8148 (27.9) 1011 (27.7) 315 (26.8) 180,130 (26.7) 25–29.9 158,267 (32.7) 26,853 (28) 14,731 (24.4) 8939 (30.6) 953 (26.1) 372 (31.6) 210,115 (31.2) ≥ 30 20,303 (4.2) 2435 (2.5) 1204 (2) 1017 (3.5) 83 (2.3) 32 (2.7) 25,074 (3.7) SES Mid-high SES 472,042 (95.5) 93,364 (96.2) 59,144 (97.3) 28,599 (97) 3600 (97.7) 1152 (97) 657,901 (95.8) Low SES 22,301 (4.5) 3710 (3.8) 1632 (2.7) 879 (3) 86 (2.3) 36 (3) 28,644 (4.2) Region Urban area 153,296 (31) 31,814 (32.8) 21,960 (36.1) 9751 (33.1) 1937 (52.6) 562 (47.3) 219,320 (31.9) Rural area 341,047 (69) 65,260 (67.2) 38,816 (63.9) 19,727 (66.9) 1749 (47.4) 626 (52.7) 467,225 (68.1) CCI 0 331,584 (67.1) 68,555 (70.6) 44,727 (73.6) 21,214 (72) 2619 (71.1) 807 (67.9) 469,506 (68.4) 1 88,339 (17.9) 17,511 (18) 10,040 (16.5) 4925 (16.7) 632 (17.1) 184 (15.5) 121,631 (17.7) ≥ 2 74,420 (15.1) 11,008 (11.3) 6009 (9.9) 3339 (11.3) 435 (11.8) 197 (16.6) 95,408 (13.9) Smoking Never 450,318 (96.6) 87,386 (94) 54,842 (93.7) 26,805 (94.9) 3395 (95.8) 1090 (96.2) 623,836 (95.9) Past 4497 (1) 1494 (1.6) 1036 (1.8) 379 (1.3) 46 (1.3) 13 (1.1) 7465 (1.1) Current 11,531 (2.5) 4092 (4.4) 2664 (4.6) 1056 (3.7) 104 (2.9) 30 (2.6) 19,477 (3) Alcohol (per week) None 401,256 (85.6) 73,285 (78.2) 45,263 (76.8) 22,953 (80.6) 2984 (83.6) 943 (82.1) 546,684 (83.5) ≤ 2/week 58,354 (12.5) 17,536 (18.7) 11,787 (20) 4847 (17) 514 (14.4) 187 (16.3) 93,225 (14.2) 3–6/week 6429 (1.4) 2143 (2.3) 1507 (2.6) 485 (1.7) 53 (1.5) 15 (1.3) 10,632 (1.6) Daily 2593 (0.6) 730 (0.8) 395 (0.7) 208 (0.7) 17 (0.5) 3 (0.3) 3946 (0.6) Physical exercise (per week) None 301,412 (64.2) 54,951 (58.7) 34,883 (59.2) 16,854 (59.2) 2031 (56.9) 601 (52.7) 410,732 (62.7) 1–2 80,022 (17.1) 18,166 (19.4) 11,710 (19.9) 5509 (19.4) 715 (20) 246 (21.6) 116,368 (17.8) 3–4 43,862 (9.3) 10,766 (11.5) 6851 (11.6) 3127 (11) 442 (12.4) 166 (14.5) 65,214 (10) 5–6 14,004 (3) 3514 (3.8) 2208 (3.7) 970 (3.4) 143 (4) 49 (4.3) 20,888 (3.2) Daily 29,993 (6.4) 6243 (6.7) 3308 (5.6) 2008 (7.1) 239 (6.7) 79 (6.9) 41,870 (6.4)
BMI Body mass index, CCI Charlson comorbidity index, COPM combined oestrogen plus progestin by manufacturer, COPP combined oestrogen plus progestin by physician, MHT menopausal hormone therapy, SES socioeconomic status. Gynaecological characteristics of women according to menopausal hormone exposure are presented in Supplementary Table S2. Data are expressed as the number (%) or median [25 percentile, 75 percentile].
Table 2 Characteristics of women with menopausal hormone therapy, Korea National Health Insurance Data, from 2002 to 2019.
MHT characteristics Tibolone Combined oestrogen plus progestin by manufacturer Oral oestrogen Combined oestrogen plus progestin by physician Topical oestrogen Total MHT Median duration (months) 25 [11–58] 24 [11–56] 15 [8–38] 16 [9–33] 14 [8–27] 22 [10–54] Duration (years) < 5 73,258 (75.5) 46,609 (76.7) 24,593 (83.4) 3225 (87.5) 1122 (94.4) 148,807 (77.4) 5–9.9 16,741 (17.2) 10,403 (17.1) 3226 (10.9) 335 (9.1) 63 (5.3) 30,768 (16) ≥ 10 7075 (7.3) 3764 (6.2) 1659 (5.6) 126 (3.4) 3 (0.3) 12,627 (6.6) Duration of previous other MHT (years) < 5 94,872 (97.7) 59,968 (98.7) 29,107 (98.7) 3130 (84.9) 1175 (98.9) 188,252 (97.9) 5–9.9 1949 (2) 729 (1.2) 324 (1.1) 398 (10.8) 13 (1.1) 3413 (1.8) ≥ 10 253 (0.3) 79 (0.1) 47 (0.2) 158 (4.3) (0) 537 (0.3) Last dosage of tibolone (per day) 1.25 mg 888 (0.9) 2.5 mg 96,081 (99) Over 5 mg 94 (0.1) Prescribed specialty Gynaecology 32,170 (33.1) 27,539 (45.3) 11,818 (40.1) 852 (23.1) 289 (24.3) 72,668 (37.8) Non-gynaecology 64,904 (66.9) 33,237 (54.7) 17,660 (59.9) 2834 (76.9) 899 (75.7) 119,534 (62.2)
MHT menopausal hormone therapy. Data are expressed as the number (%) or median [25 percentile, 75 percentile].
Melanoma developed in 249 (0.05%, 249/494,343) patients in the non-MHT group and in 70 (0.03%, 70/192,202) patients in the MHT group (Table 3). In the MHT group, melanoma developed in 31 (0.03%, 31/97,074) tibolone, 21 (0.03%, 21/60,776) COPM, 14 (0.05%, 14/29,478) oral oestrogen, 3 (0.08%, 3/3686) COPP, and 1 (0.08%, 1/1188) topical oestrogen patient, respectively. The incidence of NMSC was 1680 cases (0.34%, 1680/494,343) in the non-MHT group and 417 cases (0.22%, 417/192,202) in the MHT group. In terms of hormone use, NMSC developed in 211 (0.22%, 211/97,074) tibolone, 109 (0.18%, 109/60,776) COPM, 84 (0.28%, 84/29,478) oral oestrogen, 10 (0.27%, 10/3686) COPP, and 3 (0.25%, 3/1188) topical oestrogen patients, respectively.
Table 3 Incidence of skin cancer according to hormone exposure status at recruitment, Korea National Health Insurance Data, from 2002 to 2019.
Non-MHT Tibolone Combined oestrogen plus progestin by manufacturer Oral oestrogen Combined oestrogen plus progestin by physician Topical oestrogen Total Median period from menopause to inclusion (years) 7 [2–14] 4 [1–8.5] 2.5 [0–6.5] 4.5 [1–9] 4.5 [1–9.5] 4.5 [1–9] 6 [2–12.5] Melanoma Not present 494,094 (99.95) 97,043 (99.97) 60,755 (99.97) 29,464 (99.95) 3683 (99.92) 1187 (99.92) 686,226 (99.95) Present 249 (0.05) 31 (0.03) 21 (0.03) 14 (0.05) 3 (0.08) 1 (0.08) 319 (0.05) Non-melanoma skin cancer Not present 492,663 (99.66) 96,863 (99.78) 60,667 (99.82) 29,394 (99.72) 3676 (99.73) 1185 (99.75) 684,448 (99.69) Present 1680 (0.34) 211 (0.22) 109 (0.18) 84 (0.28) 10 (0.27) 3 (0.25) 2097 (0.31) Total skin cancer Not present 492,452 (99.62) 96,835 (99.75) 60,652 (99.8) 29,383 (99.68) 3673 (99.65) 1184 (99.66) 684,179 (99.66) Present 1891 (0.38) 239 (0.25) 124 (0.2) 95 (0.32) 13 (0.35) 4 (0.34) 2366 (0.34)
MHT menopausal hormone therapy. Data are expressed as the number (%) or median [25 percentile, 75 percentile].
MHT did not affect the incidence of melanoma in the Cox proportional regression analysis after adjusting for multiple variables (Fig. 2). We found that tibolone (hazard ratio [HR] 0.812, 95% confidence interval [CI] 0.694–0.949) and COPM (HR 0.777, 95% CI 0.63–0.962) lowered the risk of NMSC. In terms of total skin cancer, tibolone (HR 0.798, 95% CI 0.689–0.924) and COPM (HR 0.771, 95% CI 0.63–0.941) lowered the risk, while other hormone groups did not change the risk. In a subgroup analysis of tibolone only, the risk of total skin cancer did not change at 1.25 mg (half dose) of tibolone (HR 1.499, 95% CI 0.561–4.001) (Supplementary Table S3).
Graph: Figure 2Comparison of hazards of Melanoma, NMSC, and total skin cancer development among MHT subgroup. CI Confidence interval, HR Hazard ratio, MHT menopausal hormone therapy, NMSC non-melanoma skin cancer.
In the Cox proportional regression analysis, older age (≥ 70 years: HR 2.566, 95% CI 1.187–5.547) and obesity (BMI ≥ 30: HR 1.854, 95% CI 1.108–3.1) increased the risk of melanoma (Table 4). In contrast, older age (≥ 70 years: HR 5.202, 95% CI 3.767–7.183), rural areas (HR 1.272, 95% CI 1.144–1.415), age at menopause (≥ 55 years: HR 1.346, 95% CI 1.062–1.707), and long period from menopause to inclusion (≥ 10 years: HR 1.655, 95% CI 1.353–2.025) increased the risk of NMSC. However, obesity (BMI ≥ 30: HR 0.766, 95% CI 0.597–0.984), past smoking (HR 0.467, 95% CI 0.233–0.936), alcohol consumption (≤ 2/week) (HR 0.831, 95% CI 0.706–0.979), and physical exercise (1–2/week) (HR 0.805, 95% CI 0.702–0.922) lowered the risk of NMSC.
Table 4 Hazard ratios for risk of skin cancer according to major variables, Korea National Health Insurance Data, from 2002 to 2019.
Variables Melanomaa Non-melanomaa Total skin cancera HR (95% CI)a P-value HR (95% CI)a P-value HR (95% CI)a P-value MHT Tibolone 0.677 (0.453–1.013) 0.058 0.812 (0.694–0.949) 0.009 0.798 (0.689–0.924) 0.003 CEPM 0.926 (0.584–1.467) 0.74 0.777 (0.628–0.962) 0.021 0.771 (0.633–0.941) 0.01 Oral estrogen EOOOEstrogen 1.04 (0.602–1.799) 0.89 0.962 (0.76–1.217) 0.75 0.958 (0.769–1.194) 0.71 CEPP 1.753 (0.559–5.496) 0.34 0.98 (0.525–1.827) 0.95 1.11 (0.642–1.919) 0.71 Topical estrogen 1.864 (0.261–13.328) 0.54 1.025 (0.33–3.184) 0.97 1.178 (0.441–3.145) 0.74 Age at inclusion (years) 50–59 1.207 (0.731–1.994) 0.46 1.463 (1.159–1.848) 0.001 1.408 (1.137–1.743) 0.002 60–69 1.938 (0.979–3.839) 0.058 2.385 (1.769–3.216) < 0.001 2.268 (1.721–2.99) < 0.001 ≥ 70 2.566 (1.187–5.547) 0.017 5.202 (3.767–7.183) < 0.001 4.723 (3.5–6.373) < 0.001 BMI (kg/m2) < 18.5 0.439 (0.108–1.786) 0.25 0.672 (0.46–0.981) 0.04 0.662 (0.46–0.955) 0.027 23–24.9 1.408 (1.042–1.903) 0.026 0.873 (0.777–0.981) 0.023 0.92 (0.824–1.027) 0.14 25–29.9 1.342 (1.002–1.797) 0.048 0.841 (0.753–0.939) 0.002 0.894 (0.805–0.992) 0.034 ≥ 30 1.854 (1.108–3.1) 0.019 0.766 (0.597–0.984) 0.037 0.871 (0.695–1.093) 0.23 SES Low SES 1.363 (0.741–2.509) 0.32 1.217 (0.949–1.561) 0.12 1.232 (0.975–1.555) 0.08 Region Rural area 1.036 (0.806–1.331) 0.78 1.272 (1.144–1.415) < 0.001 1.242 (1.125–1.371) < 0.001 CCI 1 1.072 (0.798–1.441) 0.64 1.072 (0.954–1.204) 0.24 1.053 (0.944–1.175) 0.36 ≥ 2 1.138 (0.826–1.568) 0.43 1.096 (0.963–1.247) 0.17 1.091 (0.966–1.232) 0.16 Parity (years) 0 0.961 (0.523–1.767) 0.90 1.193 (0.915–1.556) 0.19 1.128 (0.883–1.441) 0.34 2 0.94 (0.551–1.602) 0.82 1.056 (0.829–1.344) 0.66 1.03 (0.826–1.285) 0.79 ≥ 3 0.877 (0.488–1.578) 0.66 1.042 (0.806–1.348) 0.75 1.007 (0.794–1.276) 0.96 Age at menarche (years) ≥ 13 0.835 (0.566–1.234) 0.37 0.863 (0.74–1.008) 0.063 0.873 (0.755–1.01) 0.067 Age at menopause (years) 45–49 1.058 (0.71–1.577) 0.78 1.057 (0.898–1.243) 0.50 1.079 (0.926–1.257) 0.33 50–54 1.091 (0.71–1.676) 0.69 1.224 (1.034–1.449) 0.019 1.229 (1.048–1.441) 0.011 ≥ 55 0.806 (0.419–1.552) 0.52 1.346 (1.062–1.707) 0.014 1.308 (1.044–1.638) 0.02 Smoking Past 0.641 (0.159–2.586) 0.53 0.467 (0.233–0.936) 0.032 0.504 (0.271–0.94) 0.031 Current 0.755 (0.334–1.711) 0.50 0.991 (0.735–1.338) 0.96 0.979 (0.739–1.297) 0.88 Alcohol (g/week) ≤ 2/week 1.173 (0.833–1.65) 0.36 0.831 (0.706–0.979) 0.026 0.872 (0.751–1.012) 0.071 3–6/week 0.854 (0.272–2.684) 0.79 0.907 (0.569–1.448) 0.68 0.915 (0.594–1.411) 0.69 Daily 0.619 (0.087–4.42) 0.63 0.643 (0.306–1.352) 0.24 0.652 (0.325–1.307) 0.23 Physical exercise (per week) 1–2 0.817 (0.588–1.136) 0.23 0.805 (0.702–0.922) 0.002 0.821 (0.724–0.931) 0.002 3–4 0.789 (0.515–1.208) 0.28 0.786 (0.659–0.938) 0.008 0.791 (0.671–0.933) 0.005 5–6 1.044 (0.552–1.973) 0.90 0.749 (0.551–1.019) 0.066 0.78 (0.588–1.035) 0.085 Daily 0.754 (0.465–1.223) 0.25 0.867 (0.726–1.036) 0.12 0.856 (0.724–1.013) 0.071 Period from menopause to inclusion (years) 5–9 1.249 (0.868–1.796) 0.23 1.169 (0.995–1.373) 0.057 1.184 (1.02–1.373) 0.026 ≥ 10 1.321 (0.807–2.161) 0.27 1.655 (1.353–2.025) < 0.001 1.613 (1.336–1.947) < 0.001
BMI Body mass index, CCI Charlson comorbidity index, CEPM combined oestrogen and progestin by the manufacturer, CEPP combined oestrogen and progestin by the physician (COPP), CI confidence interval, HR hazard ratio, MHT menopausal hormone therapy, SES socioeconomic status.
In this large, population-based, retrospective study, we found that MHT did not affect the incidence of melanoma in menopausal Korean women, and we did not find an association between oral oestrogen and melanoma or NMSC. Our findings are consistent with the results of the WHI trial[
In recent years, there have been only a limited number of studies investigating the association between MHT and NMSC, with the majority of them focusing on Caucasian populations. While Tang et al.[
We analysed parity, age at menarche, and age at menopause, and these variables indirectly measure physiological exposure to sex hormones. These factors were not associated with the risk of melanoma; however, age at menopause (≥ 55 years) was associated with an increased risk of NMSC. Similar to our results, a Finnish study found that the risk of BCC decreased with an increasing number of deliveries[
Additionally, our results unexpectedly showed that obesity and smoking history, which are commonly known risk factors for cancer, lowered the risk of NMSC. Karimi et al.[
Generally, smoking is considered to increase the risk of skin cancer[
This study has several strengths. A large sample size gives this study statistical power compared to other observational studies, and because it is based on nationwide registry data, it was possible to increase the accuracy of cancer incidence and minimise selection bias. This was an observational study using tibolone as the main MHT. To the best of our knowledge, there have been no previous studies on NMSC and tibolone. Considering that tibolone is the most commonly prescribed MTH drug in South Korea, our results have an implication in real practice. Finally, variables including age, BMI, SES, region, CCI, parity, the age at menarche, age at menopause, smoking, alcohol, physical exercise, and the period from menopause to inclusion were adjusted to control confounding.
Our study has several principal limitations, the first of which pertains to the use of health insurance data and the inherent risk of overestimation this carries. In Korea, C codes are allocated based on pathological confirmation, however, this does not unequivocally ensure the completeness of the data. To address this concern, we included in our analysis only those patients who had been diagnosed with skin cancer and had made three or more visits to medical institutions for their condition. Additionally, we acknowledge the absence of specific data on alcohol consumption levels and quantities of smoking. Given that the survey questions relating to these factors varied throughout the study period (2002–2011), we concentrated on consistently reported parameters: namely, the frequency of alcohol intake and the prevalence of smoking. While this focus may constrain the comprehensiveness of our findings with regards to these behaviours, we assert that our analysis continues to yield significant insights despite these limitations. Another key limitation of this study is that our data did not contain well-known risk factors for skin cancer, such as ultraviolet (UV) exposure, family history, and immune status. In Korea, the most common type of melanoma is acral lentiginous melanoma, followed by nonchronic sun damage-induced melanoma[
In conclusion, our study supports that MHT is not associated with melanoma in menopausal women. We propose that tibolone and combined oestrogen and progestin by the manufacturer may contribute to lowering the incidence of non-melanoma skin cancer in the Korean population. Further prospective studies involving multi-ethnic groups are needed to expand the results of this study.
We would like to thank Editage [
J.-S.Y. and M.S.K. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: J.-S.Y., M.S.K. Acquisition, analysis, or interpretation of data: J.-S.Y., Y.-S.S., M.-H.K. Drafting of the manuscript: J.-S.Y., M.S.K. Critical revision of the manuscript for important intellectual content: J.-S.Y., S.-K.L., J.A.U., M.S.K. Statistical analysis: J.-S.Y. Administrative, technical, or material support: J.-S.Y., S.-K.L., J.A.U., M.S.K. Supervision: S.-K.L., M.S.K.
The data that support the findings of this study are available from the corresponding author, M.S. Kim, upon reasonable request.
The authors declare no competing interests.
Graph: Supplementary Tables.
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By Jin-Sung Yuk; Soo-Kyung Lee; Ji An Uh; Yong-Soo Seo; Myounghwan Kim and Myoung Shin Kim
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