Table 1.
The detailed characteristics of the included studies.
| References | Country (year) | Age | Study design | Years of follow-up | Participants (cases) | Cancer type | Hormone type | RR (95% CI) | Adjustment for covariant |
|---|---|---|---|---|---|---|---|---|---|
| Danforth et al. (46) | America (2007) | 61.2 (mean) | Cohort | 26 years | 82,950 (389) | Ovarian cancer | HRT | 1.41 (1.07, 1.86) | Age, parity, duration of oral contraceptive use, tubal ligation, age at natural menopause, age at menarche |
| Danforth et al. (46) | America (2007) | 61.2 (mean) | Cohort | 26 years | 82,950 (233) | Serous tumors | HRT | 1.66 (1.17, 2.36) | Age, parity, duration of oral contraceptive use, tubal ligation, age at natural menopause, age at menarche |
| Danforth et al. (46) | America (2007) | 61.2 (mean) | Cohort | 26 years | 82,950 (60) | Endometrioid tumors | HRT | 1.86 (0.89, 3.91) | Age, parity, duration of oral contraceptive use, tubal ligation, age at natural menopause, age at menarche |
| Bethea et al. (30) | America (2017) | 37.8 ± 10.3 | Cohort | 18 years | 59,000 (115) | Ovarian cancer | HRT | 1.42 (0.75, 2.70) | Age, questionnaire cycle, parity, lactation, age at first birth, age at last birth, hysterectomy, tubal ligation, oral contraceptive use, educational HRT attainment, and BMI |
| Li et al. (25) | 10 European countries (2015) | 52.4 (median) | Cohort | 11.7 years | 367,903 (791) | Ovarian cancer | HRT | 1.09 (0.92, 1.30) | Menopausal status, age at menopause, age at menarche, number of full-term pregnancies (FTPs), age at first FTP, duration of breast-feeding, number of miscarriages, unilateral ovariectomy, hysterectomy, HRT, OC use, IUD use, BMI, smoking status, alcohol consumption, and pre-existing diabetes |
| Soegaard et al. (38) | Denmark (2007) | 35-79 | Case control | NA | 1,614 (50) | Mucinous tumors | HRT | 0.71 (0.37, 1.36) | Age, pregnancy, additional pregnancies and duration of oral contraceptive use |
| Soegaard et al. (38) | Denmark (2007) | 35-79 | Case control | NA | 1,907 (343) | Serous tumors | HRT | 1.30 (1.00, 1.68) | Age, pregnancy, additional pregnancies and duration of oral contraceptive use |
| Soegaard et al. (38) | Denmark (2007) | 35-79 | Case control | NA | 1,639 (75) | Endometrioid tumors | HRT | 1.75 (1.07, 2.84) | Age, pregnancy, additional pregnancies and duration of oral contraceptive use |
| Soegaard et al. (38) | Denmark (2007) | 35-79 | Case control | NA | 1,650 (86) | Other types of ovarian cancer | HRT | 1.43 (0.90, 2.28) | Age, pregnancy, additional pregnancies and duration of oral contraceptive use |
| Soegaard et al. (38) | Denmark (2007) | 35-79 | Case control | NA | 2,118 (554) | Ovarian cancer | HRT | 1.30 (1.05, 1.61) | Age, pregnancy, additional pregnancies and duration of oral contraceptive use |
| Koskela-Niska et al. (39) | Finland (2013) | > 50 | Case control | NA | 15,283 (3,958) | Ovarian cancer | HRT | 1.15 (0.99, 1.32) | Age and place of residence |
| Koskela-Niska et al. (39) | Finland (2013) | > 50 | Case control | NA | 7,333 (1,903) | Serous tumors | HRT | 1.45 (1.20, 1.75) | Age and place of residence |
| Koskela-Niska et al. (39) | Finland (2013) | > 50 | Case control | NA | 2,901 (748) | Endometrioid tumors | HRT | 1.25 (0.88, 1.76) | Age and place of residence |
| Koskela-Niska et al. (39) | Finland (2013) | > 50 | Case control | NA | 1,611 (417) | Mucinous tumors | HRT | 0.35 (0.19, 0.67) | Age and place of residence |
| Koskela-Niska et al. (39) | Finland (2013) | > 50 | Case control | NA | 596 (155) | Clear cell tumors | HRT | 0.72 (0.23, 2.29) | Age and place of residence |
| Koskela-Niska et al. (39) | Finland (2013) | > 50 | Case control | NA | 2,842 (735) | Other types of ovarian cancer | HRT | 0.82 (0.56, 1.20) | Age and place of residence |
| Folsom et al. (11) | America (2004) | 55-69 | Cohort | 15 years | 31,381 (174) | Ovarian cancer | ERT | 2.53 (1.44, 4.45) | Age, family history of ovarian cancer in a first- or second-degree relative, hysterectomy, unilateral oophorectomy, number of live births, physical activity index, pack-years of smoking, waist/hip ratio, and BMI |
| Risch (40) | Canada (1996) | Case: 59.5, control: 57.5 (mean) | Case control | NA | 776 (212) | Serous tumors | ERT | 2.03 (1.04, 3.97) | Age, number of full-term pregnancies, total years of oral-contraceptive use, and average lactation/pregnancy as continuous terms, and history of tubal ligation, hysterectomy, and mother/sister with breast cancer as dichotomous terms |
| Risch (40) | Canada (1996) | Case: 59.5, control: 57.5 (mean) | Case control | NA | 637 (73) | Endometrioid tumors | ERT | 2.81 (1.15, 6.89) | Age, number of full-term pregnancies, total years of oral-contraceptive use, and average lactation/pregnancy as continuous terms, and history of tubal ligation, hysterectomy, and mother/sister with breast cancer as dichotomous terms |
| Risch (40) | Canada (1996) | Case: 59.5, control: 57.5 (mean) | Case control | NA | 604 (40) | Mucinous tumors | ERT | 0.58 (0.08, 4.21) | Age, number of full-term pregnancies, total years of oral-contraceptive use, and average lactation/pregnancy as continuous terms, and history of tubal ligation, hysterectomy, and mother/sister with breast cancer as dichotomous terms |
| Risch (40) | Canada (1996) | Case: 59.5, control: 57.5 (mean) | Case control | NA | 891 (327) | Ovarian cancer | ERT | 1.77 (0.98, 3.20) | Age, number of full-term pregnancies, total years of oral-contraceptive use, and average lactation/pregnancy as continuous terms, and history of tubal ligation, hysterectomy, and mother/sister with breast cancer as dichotomous terms |
| Perri et al. (12) | Israeli (2015) | Case: 53.6 ± 10.3, control: 49.1 ± 13.4 | Cohort | 18 years | 1,073 (175) | Ovarian cancer | HRT | 1.98 (1.21, 3.25) | Mutation type, age at menarche, oral contraceptive use, parity, age at first pregnancy |
| Bakken et al. (26) | Norway (2004) | 53.0 (mean) | Cohort | 7 years | 30,115 (74) | Ovarian cancer | HRT | 1.30 (0.80, 2.00) | Age, BMI, smoking, ever use of OCs, time since menopause, parity and age at last birth |
| Mills et al. (41) | America (2005) | NA | Case control | NA | 1,378 (256) | Ovarian cancer | HRT | 1.39 (1.01, 1.93) | Age, race/ethnicity, duration of oral contraceptive use and breastfeeding |
| Mills et al. (41) | America (2005) | NA | Case control | NA | 1,214 (92) | Serous tumors | HRT | 1.61 (0.99, 2.60) | Age, race/ethnicity, duration of oral contraceptive use and breastfeeding |
| Mills et al. (41) | America (2005) | NA | Case control | NA | 1,157 (35) | Endometrioid tumors | HRT | 0.96 (0.44, 2.10) | Age, race/ethnicity, duration of oral contraceptive use and breastfeeding |
| Mills et al. (41) | America (2005) | NA | Case control | NA | 1,138 (16) | Mucinous tumors | HRT | 1.32 (0.40, 4.40) | Age, race/ethnicity, duration of oral contraceptive use and breastfeeding |
| Mills et al. (41) | America (2005) | NA | Case control | NA | 1,134 (12) | Clear cell tumors | HRT | 1.14 (0.27, 4.84) | Age, race/ethnicity, duration of oral contraceptive use and breastfeeding |
| Mills et al. (41) | America (2005) | NA | Case control | NA | 1,149 (27) | Other types of ovarian cancer | HRT | 1.30 (0.57, 2.97) | Age, race/ethnicity, duration of oral contraceptive use and breastfeeding |
| Purdie et al. (23) | Australia (1999) | 18-79 | Case control | NA | 1,648 (793) | Ovarian cancer | HRT | 1.20 (0.90, 1.60) | Age, education, area of residence, BMI, hysterectomy, tubal sterilization, talc use in perineal region, smoking status, duration of OCP use, parity and a family history of breast or ovarian cancer |
| Riman et al. (42) | Sweden (2002) | Case: 62.4 ± 7.4, control: 63.4 ± 7.1 | Case control | NA | 4,432 (642) | Ovarian cancer | ERT | 2.10 (0.99, 4.48) | Age, parity,BMI (kg/m2), age at menopause, hysterectomy,duration of oral contraceptive use, and ever use of estrogen only (estrogen replacement therapy [ERT]) and continuous estrogen–progestin combinations (HRTcp) as categorized variables |
| Riman et al. (42) | Sweden (2002) | Case: 62.6 ± 7.3, control: 63.4 ± 7.1 | Case control | NA | 4,123 (333) | Serous tumors | ERT | 2.51 (1.00, 6.34) | Age, parity,BMI (kg/m2), age at menopause, hysterectomy,duration of oral contraceptive use, and ever use of estrogen only (estrogen replacement therapy [ERT]) and continuous estrogen–progestin combinations (HRTcp) as categorized variables |
| Riman et al. (42) | Sweden (2002) | Case: 61.6 ± 7.6, control: 63.4 ± 7.1 | Case control | NA | 3,967 (177) | Endometrioid tumors | ERT | 2.24 (0.64, 7.89) | Age, parity,BMI (kg/m2), age at menopause, hysterectomy,duration of oral contraceptive use, and ever use of estrogen only (estrogen replacement therapy [ERT]) and continuous estrogen–progestin combinations (HRTcp) as categorized variables |
| Riman et al. (42) | Sweden (2002) | Case: 62.5 ± 7.8, control: 63.4 ± 7.1 | Case control | NA | 3,850 (60) | Mucinous tumors | ERT | 1.59 (0.19, 13.33) | Age, parity,BMI (kg/m2), age at menopause, hysterectomy,duration of oral contraceptive use, and ever use of estrogen only (estrogen replacement therapy [ERT]) and continuous estrogen–progestin combinations (HRTcp) as categorized variables |
| Kotsopoulos et al. (22) | America (2006) | Case: 62.7, control: 61.2 (mean) | Case control | NA | 537 (162) | Ovarian cancer | HRT | 0.93 (0.56, 1.56) | Parity, OC use and country of residence |
| Hempling et al. (21) | America (1997) | Case: 54.9, control: 54.9 (mean) | Case control | NA | 1,255 (499) | Ovarian cancer | HRT | 0.60 (0.30, 1.40) | Age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, location, and education |
| Hempling et al. (21) | America (1997) | Case: 54.9, control: 54.9 (mean) | Case control | NA | NA | Serous tumors | HRT | 1.20 (0.80, 1.70) | NA |
| Hempling et al. (21) | America (1997) | Case: 54.9, control: 54.9 (mean) | Case control | NA | NA | Clear cell tumors | HRT | 1.10 (0.40, 3.40) | NA |
| Hempling et al. (21) | America (1997) | Case: 54.9, control: 54.9 (mean) | Case control | NA | NA | Endometrioid tumors | HRT | 0.40 (0.20, 1.20) | NA |
| Sit et al. (24) | America (2002) | Case: 56.6, control: 55.7 (mean) | Case control | NA | 1,410 (848) | Ovarian cancer | HRT | 1.03 (0.69, 1.53) | Numbers of live births, family history of ovarian carcinoma,OC use, history of tubal ligation, and age at diagnosis |
| Mørch et al. (43) | Denmark (2012) | ≥50 | Cohort | 8 years | 909,946 (1,336) | Serous tumors | HRT | 1.64 (1.41, 1.89) | Age, time period, number of births, educational level, and history of hysterectomy, sterilization, unilateral oophorectomy or salpingo-oophorectomy, endometriosis, and infertility |
| Mørch et al. (43) | Denmark (2012) | ≥50 | Cohort | 8 years | 909,946 (377) | Endometrioid tumors | HRT | 1.81 (1.39, 2.36) | Age, time period, number of births, educational level, and history of hysterectomy, sterilization, unilateral oophorectomy or salpingo-oophorectomy, endometriosis, and infertility |
| Mørch et al. (43) | Denmark (2012) | ≥50 | Cohort | 8 years | 909,946 (293) | Mucinous tumors | HRT | 0.74 (0.51, 1.08) | Age, time period, number of births, educational level, and history of hysterectomy, sterilization, unilateral oophorectomy or salpingo-oophorectomy, endometriosis, and infertility |
| Mørch et al. (43) | Denmark (2012) | ≥50 | Cohort | 8 years | 909,946 (159) | Clear cell tumors | HRT | 0.81 (0.50, 1.32) | Age, time period, number of births, educational level, and history of hysterectomy, sterilization, unilateral oophorectomy or salpingo-oophorectomy, endometriosis, and infertility |
| Morch et al. (13) | Denmark (2009) | ≥50 | Cohort | 8 years | 909,946 (2,297) | Ovarian cancer | HRT | 1.57 (1.26, 1.95) | Age, period of use, number of births, hysterectomy, sterilization, unilateral oophorectomy or salpingo-oophorectomy, endometriosis, infertility, and educational status |
| Wernli et al. (27) | America (2008) | 40-79 | Case control | NA | 6,559 (751) | Ovarian cancer | HRT | 1.24 (0.97, 1.60) | BMI, oral contraceptive use, tubal ligation, parity, family history of ovarian cancer, hysterectomy, and menopausal status |
| Urban et al. (14) | America (2015) | 50-79 | Cohort | 12.3 years | 74,786 (461) | Ovarian cancer | HRT | 1.50 (1.23, 1.83) | Age and race |
| Tavani et al. (15) | Italy (2000) | Case: 54.0, control: 52.0 (mean) | Case control | NA | 232 (93) | Ovarian cancer | HRT | 1.80 (1.30, 2.60) | Age and area of residence |
| Lacey et al. (16) | America (2002) | 56.6 (mean) | Cohort | 13.4 years | 44,241 (275) | Ovarian cancer | ERT | 3.20 (1.70, 5.70) | Age, menopause type, and duration of oral contraceptive use |
| Simin et al. (17) | Sweden (2017) | ≥40 | Cohort | 7 years | 290,186 (573) | Ovarian cancer | HRT | 1.09 (1.00, 1.19) | NA |
| Yang et al. (45) | America (2012) | Case: 62.8 ± 5.3, control: 61.8 ± 5.4 | Cohort | Case: 5.1 years; control: 9.8 years | 168,323 (849) | Ovarian cancer | HRT | 1.57 (1.31, 1.89) | Age, oral contraceptive use, parity, menopausal hormone therapy |
| Yang et al. (45) | America (2012) | Case: 62.6 ± 5.4, control: 61.8 ± 5.4 | Cohort | Case: 5.1 years; control: 9.8 years | 168,323 (449) | Serous tumors | HRT | 1.64 (1.27, 2.13) | Age, oral contraceptive use, parity, menopausal hormone therapy |
| Yang et al. (45) | America (2012) | Case: 61.0 ± 6.2, control: 61.8 ± 5.4 | Cohort | Case: 5.1 years; control: 9.8 years | 168,323 (78) | Endometrioid tumors | HRT | 2.27 (1.26, 4.09) | Age, oral contraceptive use, parity, menopausal hormone therapy |
| Yang et al. (45) | America (2012) | Case: 63.5 ± 5.5, control: 61.8 ± 5.4 | Cohort | Case: 5.1 years; control: 9.8 years | 169,391 (37) | Mucinous tumors | HRT | 0.50 (0.17, 1.42) | Age, oral contraceptive use, parity, menopausal hormone therapy |
| Yang et al. (45) | America (2012) | Case: 59.7 ± 6.2, control: 61.8 ± 5.4 | Cohort | Case: 5.1 years; control: 9.8 years | 168,323 (26) | Clear cell tumors | HRT | 1.82 (0.64, 5.17) | Age, oral contraceptive use, parity, menopausal hormone therapy |
| Yang et al. (45) | America (2012) | Case: 63.9 ± 4.8, control: 61.8 ± 5.4 | Cohort | Case: 5.1 years; control: 9.8 years | 168,323 (255) | Other types of ovarian cancer | HRT | 1.53 (1.11, 2.13) | Age, oral contraceptive use, parity, menopausal hormone therapy |
| Rossing et al. (18) | America (2007) | Case: 47.0, control: 48.0 (median) | Case control | NA | 1,818 (715) | Ovarian cancer | ERT | 1.60 (1.10, 2.50) | Age, county of residence, year of diagnosis/reference date, number of full-term pregnancies, and duration of hormonal contraception |
| Moorman et al. (44) | America (2005) | 20-74 | Case control | NA | 734 (364) | Ovarian cancer | HRT | 1.20 (0.80, 1.60) | Age, race, parity, tubal ligation, hysterectomy, BMI 1 year before interview, 1st degree family history of breast or ovarian cancer, breastfeeding, oral contraceptive use, and educational level |
| Moorman et al. (44) | America (2005) | 20-74 | Case control | NA | 572 (216) | Serous tumors | HRT | 2.00 (1.30, 3.10) | Age and race |
| Moorman et al. (44) | America (2005) | 20-74 | Case control | NA | 421 (65) | Endometrioid tumors | HRT | 1.00 (0.50, 2.00) | Age and race |
| Moorman et al. (44) | America (2005) | 20-74 | Case control | NA | 382 (25) | Mucinous tumors | HRT | 0.90 (0.30, 2.50) | Age and race |
| Moorman et al. (44) | America (2005) | 20-74 | Case control | NA | 397 (40) | Other types of ovarian cancer | HRT | 1.10 (0.50, 2.70) | Age and race |
| Beral et al. (19) | United Kingdom (2007) | 57.2 ± 4.6 | Cohort | 5.3 years | 948,576 (2,273) | Ovarian cancer | HRT | 1.31 (1.12, 1.53) | Region of residence, socioeconomic group,time since menopause, parity, BMI, alcohol consumption, and use of oral contraceptives |
| Koskela-Niska et al. (39) | Finland (2013) | ≥50 | Cohort | 12 years | 224,015 (602) | Ovarian cancer | HRT | 1.13 (0.74, 1.64) | Age |
| Rasmussen et al. (29) | Denmark (2017) | NA | Case control | NA | 14,007 (885) | Ovarian cancer | HRT | 1.34 (0.86, 2.09) | Age, tubal ligation, salpingectomy, hysterectomy, endometriosis, pelvic inflammatory disease, infertility, parity, and hormone replacement therapy |
| Chiaffarino et al. (31) | Italy (2001) | Case: 56.0, control: 57.0 (median) | Case control | NA | 3,442 (1031) | Ovarian cancer | HRT | 1.40 (0.80, 2.50) | Age, center education, parity, OC use. and family history of ovarian and breast cancer in first degree relative |
| Braem et al. (32) | Netherlands (2010) | Case: 62.0, control: 61.5 (mean) | cohort | 16 years | 2,706 (375) | Ovarian cancer | HRT | 0.97 (0.69, 1.37) | Age, parity, duration of OC and HRT use |
| Pasalich et al. (33) | China (2013) | Case: 59.0 ± 5.6, control: 59.7 ± 6.4 | Case control | NA | 1,000 (500) | Ovarian cancer | HRT | 1.05 (0.35, 3.21) | Age, smoking status, alcohol drinking, education, BMI,mutually adjusted for parity, oral contraceptive use, hormone replacement therapy, menopausal status, hysterectomy and family history of ovarian and/or breast cancer |
| Salazar-Martinez et al. (34) | Mexico (1999) | Case: 52.8, control: 54.6 (mean) | Case control | NA | 752 (84) | Ovarian cancer | HRT | 1.00 (0.36, 2.70) | Age, anovulatory index, smoking, diabetes mellitus, hypertension, physical activity, menopausal status, and body build index |
| Jordan et al. (35) | Australia (2007) | 18-79 | Case control | NA | 885 (133) | Mucinous tumors | HRT | 0.67 (0.28, 1.64) | Age, state of residence, education, parity, hysterectomy, smoking status |
| Jordan et al. (35) | Australia (2007) | 18-79 | Case control | NA | 982 (230) | Serous tumors | HRT | 0.71 (0.40, 1.27) | Age, state of residence, education, parity, hysterectomy, smoking status |
| Jordan et al. (35) | Australia (2007) | 18-79 | Case control | NA | 1,115 (363) | Ovarian cancer | HRT | 0.70 (0.42, 1.17) | Age, state of residence, education, parity, hysterectomy, smoking status |
| Polychronopoulou et al. (20) | Greece (1993) | <75 | Case control | NA | 389 (189) | Ovarian cancer | HRT | 5.73 (1.07, 30.80) | Age, years of schooling, weight before the disease, age at menarche, parity and age at first birth |
| Adami et al. (36) | Sweden (1989) | 54.5 (mean) | cohort | 6.7 years | 23,244 (64) | Ovarian cancer | HRT | 0.96 (0.74, 1.23) | NA |
| Schneider et al. (37) | United Kingdom (2009) | 51.3 ± 6.1 | Case control | NA | 602 (86) | Ovarian cancer | HRT | 0.97 (0.61, 1.54) | Smoking status, BMI, use of oral contraceptives, progesterone preparations and vaginal estrogens |
RR, relative risk; CI, confidence interval; BMI, body mass index; NA, not available; HRT, hormone replacement therapy; ERT, estrogen replacement therapy.