DOI: https://doi.org/10.18370/2309-4117.2013.14.23-30

Non-contraceptive benefits of oral hormonal contraceptives

Adolf E. Schindler

Abstract


It is becoming evident that oral hormonal contraceptives-besides being well established contraceptives-seem to become important medications for many functional or organic disturbances. So far, clinical eff ectiveness has been shown for treatment as well as prevention of menstrual bleeding disorders and menstrualrelated pain symptoms. Also this is true for premenstrual syndrome and premenstrual disphoric disorder.
Particular oral contraceptives (OCs) containing anti-androgenic progestogens were shown to be eff ective medications for treatment of androgenisation symptoms (seborrhea, acne, hirsutism, alopecia).
Through perfect suppression of the hypothalamic-pituitary-ovarian axis OCs have proven to be eff ective in elimination of persistent follicular cysts. Endometriosis/adenomyosis related pain symptoms are well handled similar to other drugs like Gonadotropine Releasing Hormone agonists but are less expensive, with less side eff ects, and possibility to be used for longer periods of time. This is also true for myoma. Pelvic infl ammatory disease, rheumatoid arthritis, menstrual migraine, and onset of multiple sclerosis are prevented or delayed. Bone density is preserved and asthma symptoms improved. Endometrial hyperplasia and benign breast disease can be controlled. There is defi nitely a signifi cant impact on risk reduction regarding endometrial, ovarian, and colon cancers.
In conclusion, it needs to be recognized that oral combined hormonal contraceptives (estrogen/progestogen combination) are – besides being reliable forms of contraception – are cost-eff ective medications for many medical disorders in women. Therefore, these contraceptives drugs are important for female health and should be used in clinical practice.


Keywords


oral hormonal contraceptives; therapeutics; prevention

References


Fraser IS Non-contraceptive health benefi ts of intrauterine hormonal systems. Contracepti on.2010;82(5):396–403. doi: 10.1016/j.contraception.2010.05.005.

Asbell B The pill: a biography of the drug that changed the world. Random House New York; 1995.

Kaunitz AM Oral contraceptive health benefi ts: perception versus reality. Contraception. 1999;59(1 Suppl):29S–33S. doi: 10.1016/S0010-7824(98)00135-8.

Jensen JT The befi ts of reduced menstrual bleeding associated with the use of contraceptive methods. Gynecol Forum. 2010;15:10–4.

Fraser IS, Porte RJ, Kouides PA, Lukes ASA benefi t-risk review of systemic haemostatic agents: part 1: in major surgery. Drug Saf. 2008;31(3):217–30. doi: 10.2165/00002018-200831030-00003.

Maia HJ, Casoy J Non-contraceptive health benefi ts of oral contraceptives. Eur J Contracept Reprod Health Care. 2008;13(1):17–24.

Schindler AE Non-contraceptive use of hormonal contraceptives for women with various medical problems. J Pediat Obstet Gynecol. 2008;34:183–200.

Schindler AE Antiandrogenic progestins for treatment of signs of androgenisation and hormonal contraception. Eur J Obstet Gynecol Reprod Biol. 2004;112:136–41. doi: 10.1016/j.ejogrb.2003.09.030.

Falsetti L, Gambera A, Tisi GEffi cacy of the combination ethinyl oestradiol and cyproterone acetate on endocrine, clinical and ultrasonographic profi le in polycystic ovarian syndrome. Hum Reprod.2001;16(1):36–42. doi: 10.1093/humrep/16.1.36.

Venturoli S, Paradisi R, Saviotti E, Porcu E, Fabbsi R, Orsini LF Ulrtasouns study of ovarian and uterine morphology in women with PCOS before, during and after treatment with CPA and EE. Arch Gynecol. 1987;237:1–10. doi: 10.1007/BF02133945.

Schindler AE, Mangold K, Friedrich E, Keller E, Göser R Therapy of androgenetic symptomatology with cyproterone acetate and ethinyl estradiol. Arch Gyn Obst. 1978;225(2):103–7.

Huber JC, Bentz EK, Ott J Tempfer CB. Non-contraceptive benefi ts of oral contraceptives. Expert Opin Pharmacother. 2008;9(13):2317–25. doi: 10.1517/14656566.9.13.2317.

Sillem M Yasminelle((R)): a new low-dose combined oral contraceptive containingdrospirenone.Womens Health (Lond Engl). 2006;2(4):551–9. doi: 10.2217/17455057.2.4.551.

Westhoff C, Clark CJ Benign ovarian cysts in England and Wales and in the United States. Br J Obstet Gynaecol. 1992;99(4):329–32. doi: 10.1111/j.1471-0528.1992.tb13733.x.

Schindler AE Pathophysiology, diagnosis and treatment of endometriosis. Minerva Ginecol.2004;56(5):419–35.

Adamson D Endometriosis: traditional perspectives, current evidence and future possibilities. Int J Fertil Womens Med. 2001;46(3):151–68.

Haider Z, D’Souza R Non-contraceptive benefi ts and risks of contraception. Best Pract Res Clin Obstet Gynaecol. 2009;23(2):249–62. doi: 10.1016/j.bpobgyn.2008.12.003.

Seracchioli R, Mabrouk M, Manuzzi L, Vicenzi C, Frasca C, Elmakky A et al. Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis. Hum Reprod. 2009;24(11):2729–35. doi: 10.1093/humrep/dep259.

Vercellini P, Pietropaolo G, De Giorgi O, Pasin R, Chiodini A, Crosignani PG Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril. 2005;84(5):1375–87. doi: 10.1016/j.fertnstert.2005.03.083.

Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Crosignani PG Endometriosis: current therapies and new pharmacological developments. Drugs. 2009;69(6):649–75. doi: 10.2165/00003495-200969060-00002.

Maia H, Jr., Casoy J, Correia T, Freitas L, Pimentel K, Athayde C Eff ect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis. Gynecol Endocrinol. 2006;22(10):547–51. doi: 10.1080/09513590601005375.

Ross RK, Pike MC, Vessey MP, Bull D, Yeates D, Casagrande JT Risk factors for uterine fi broids: reduced risk associated with oral contraceptives. Br Med J (Clin Res Ed). 1986;293(6543):359–62. doi: 10.1136/bmj.293.6543.359.

Chiaff arino F, Parazzini F, La Vecchia C, Marsico S, Surace M, Ricci E Use of oral contraceptives and uterine fi broids: results from a case-control study. Br J Obstet Gynaecol. 1999;106(8):857–60. doi: 10.1111/j.1471-0528.1999.tb08409.x.

Burkman RT Oral contraceptives: current status. Clin Obstet Gynecol. 2001;44(1):62–72. doi: 10.1097/00003081-200103000-00010.

Spector TD, Hochberg MC The protective eff ect of the oral contraceptive pill on rheumatoid arthritis: an overview of the analytic epidemiological studies using meta-analysis. J Clin Epidemiol.1990;43(11):1221–30. doi: 10.1016/0895-4356(90)90023-I.

Jorgensen C, Picot MC, Bologna C, Sany J Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis. Ann Rheum Dis. 1996;55(2):94–8. doi: 10.1136/ard.55.2.94.

Drossaers-Bakker KW, Zwinderman AH, van Zeben D, Breedveld FC, Hazes JM Pregnancy and oral contraceptive use do not signifi cantly infl uence outcome in long term rheumatoid arthritis. Ann Rheum Dis. 2002;61(5):405–8. doi: 10.1136/ard.61.5.405.

Holmqvist ST, Hammar M, Lindblom AM, Brynhirdsen J Age at onset of Multiple sclerosis is correlated to use of combined oral hormonal contraceptives and child birth before diagnosis. Fert Steril.2010;94:2835–7. doi: 10.1016/j.fertnstert.2010.06.045.

Kuhl H, Birkhauser M, Mueck A, Neulen J, Thaler C, Kiesel L et al. [Long-cycle treatment in oral contraception]. Ther Umsch. 2009;66(2):101–8. doi: 10.1024/0040-5930.66.2.101.

Sulak P, Willis S, Kuehl T, Coff ee A, Clark J Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache. 2007;47(1):27–37. doi: 10.1111/j.1526-4610.2007.00650.x.

Williams JK Noncontraceptive benefi ts of oral contraceptive use: an evidence-based approach. Int J Fertil Womens Med. 2000;45(3):241–7.

La FM, Ledger WL, Davidson JW, Howard DM, Jones GL The eff ects of a third generation combined oral contraceptive pill on the classical singing voice. J Voice. 2007;21(6):754–61. doi: 10.1016/j.jvoice.2006.05.009.

Mandhane PJ, Hanna SE, Inman MD, Duncan JM, Greene JM, Wang HY et al. Changes in exhaled nitric oxide related to estrogen and progesterone during the menstrual cycle. Chest.2009;136(5):1301–7. doi: 10.1378/chest.09-0604.

Royal College of General Practitioners’ Oral Contraception Study. Eff ect on hypertension and benign breast disease of progestogen component in combined oral contraceptives. Lancet. 1977;1:624.

Brinton LA, Vessey MP, Flavel R, Yeates D Risk factors for benign breast disease. Am J Epidemiol.1981;113(3):203–14.

Siskind V, Green A, Bain C, Purdie D Beyond ovulation: oral contraceptives and epithelial ovarian cancer. Epidemiology. 2000;11(2):106–10. doi: 10.1097/00001648-200003000-00005.

The reduction in risk of ovarian cancer associated with oralcontraceptive use. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. N Engl J Med. 1987;316(11):650–5. doi: 10.1056/NEJM198703123161102.

Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner’s oral contraception study.BMJ. 2007;335(7621):651. doi: 10.1136/bmj.39289.649410.55.

World Health Organization, IARC IARC Monographs on the evaluation of carcinogenic risk to humans. Hormonal contraception and postmenopausal hormonal therapy. Lyon: 1999.

Tworoger SS, Fairfi eld KM, Colditz GA, Rosner BA, Hankinson SE Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol.2007;166(8):894–901. doi: 10.1093/aje/kwm157.

Vessey M, Painter R Oral contraceptive use and cancer. Findings in a large cohort study, 1968-2004. Br J Cancer. 2006;95(3):385–9. doi: 10.1038/sj.bjc.6603260.

Beral V, Doll R, Hermon C, Peto R, Reeves G Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet.2008;371(9609):303–14. doi: 10.1016/S0140-6736(08)60167-1.

Schlesselman JJ Net eff ect of oral contraceptive use on the risk of cancer in women in the United States. Obstet Gynecol. 1995;85(5 Pt 1):793–801. doi: 10.1016/0029-7844(95)00022-J.

McLaughlin JR, Risch HA, Lubinski J, Moller P, Ghadirian P, Lynch H et al. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet Oncol. 2007;8(1):26–34. doi: 10.1016/S1470-2045(06)70983-4.

Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis.Am J Obstet Gynecol. 2004;191(3):733–40. doi: 10.1016/j.ajog.2004.03.035.

Noncontraceptive health benefi ts of combined oral contraception Hum Reprod Update.2005;11(5):513–25. doi: 10.1093/humupd/dmi019.

Weiderpass E, Adami HO, Baron JA, Magnusson C, Lindgren A, Persson I Use of oral contraceptives and endometrial cancer risk (Sweden). Cancer Causes Control. 1999;10(4):277–84. doi: 10.1023/A:1008945721786.

Xu WH, Xiang YB, Ruan ZX, Zheng W, Cheng JR, Dai Q et al. Menstrual and reproductive factors and endometrial cancer risk: Results from a population-based case-control study in urban Shanghai. Int J Cancer. 2004;108(4):613–9. doi: 10.1002/ijc.11598.

Fernandez E, La Vecchia C, Balducci A, Chatenoud L, Franceschi S, Negri E Oral contraceptives and colorectal cancer risk: a meta-analysis. Br J Cancer. 2001;84(5):722–7. doi: 10.1054/bjoc.2000.1622.

Furner SE, Davis FG, Nelson RL, Haenszel W A case-control study of large bowel cancer and hormone exposure in women. Cancer Res. 1989;49(17):4936–40.

Schindler AE. Long-term use of progestogens: colon adenoma and colon carcinoma. Gynecol Endocrinol. 2007;23:42–4. doi: 10.1080/09513590701584899.

Weiss NS, Daling JR, Chow WH Incidence of cancer of the large bowel in women in relation to reproductive and hormonal factors. J Natl Cancer Inst. 1981;67(1):57–60.

Britt K, Short R The plight of nuns: hazards of nulliparity. Lancet. 2012;379(9834):2322–3. doi: 10.1016/S0140-6736(11)61746-7.


GOST Style Citations


Fraser IS Non-contraceptive health benefi ts of intrauterine hormonal systems. Contracepti on.2010;82(5):396–403. doi: 10.1016/j.contraception.2010.05.005.

Asbell B The pill: a biography of the drug that changed the world. Random House New York; 1995.

Kaunitz AM Oral contraceptive health benefi ts: perception versus reality. Contraception. 1999;59(1 Suppl):29S–33S. doi: 10.1016/S0010-7824(98)00135-8.

Jensen JT The befi ts of reduced menstrual bleeding associated with the use of contraceptive methods. Gynecol Forum. 2010;15:10–4.

Fraser IS, Porte RJ, Kouides PA, Lukes ASA benefi t-risk review of systemic haemostatic agents: part 1: in major surgery. Drug Saf. 2008;31(3):217–30. doi: 10.2165/00002018-200831030-00003.

Maia HJ, Casoy J Non-contraceptive health benefi ts of oral contraceptives. Eur J Contracept Reprod Health Care. 2008;13(1):17–24.

Schindler AE Non-contraceptive use of hormonal contraceptives for women with various medical problems. J Pediat Obstet Gynecol. 2008;34:183–200.

Schindler AE Antiandrogenic progestins for treatment of signs of androgenisation and hormonal contraception. Eur J Obstet Gynecol Reprod Biol. 2004;112:136–41. doi: 10.1016/j.ejogrb.2003.09.030.

Falsetti L, Gambera A, Tisi GEffi cacy of the combination ethinyl oestradiol and cyproterone acetate on endocrine, clinical and ultrasonographic profi le in polycystic ovarian syndrome. Hum Reprod.2001;16(1):36–42. doi: 10.1093/humrep/16.1.36.

Venturoli S, Paradisi R, Saviotti E, Porcu E, Fabbsi R, Orsini LF Ulrtasouns study of ovarian and uterine morphology in women with PCOS before, during and after treatment with CPA and EE. Arch Gynecol. 1987;237:1–10. doi: 10.1007/BF02133945.

Schindler AE, Mangold K, Friedrich E, Keller E, Göser R Therapy of androgenetic symptomatology with cyproterone acetate and ethinyl estradiol. Arch Gyn Obst. 1978;225(2):103–7.

Huber JC, Bentz EK, Ott J Tempfer CB. Non-contraceptive benefi ts of oral contraceptives. Expert Opin Pharmacother. 2008;9(13):2317–25. doi: 10.1517/14656566.9.13.2317.

Sillem M Yasminelle((R)): a new low-dose combined oral contraceptive containingdrospirenone.Womens Health (Lond Engl). 2006;2(4):551–9. doi: 10.2217/17455057.2.4.551.

Westhoff C, Clark CJ Benign ovarian cysts in England and Wales and in the United States. Br J Obstet Gynaecol. 1992;99(4):329–32. doi: 10.1111/j.1471-0528.1992.tb13733.x.

Schindler AE Pathophysiology, diagnosis and treatment of endometriosis. Minerva Ginecol.2004;56(5):419–35.

Adamson D Endometriosis: traditional perspectives, current evidence and future possibilities. Int J Fertil Womens Med. 2001;46(3):151–68.

Haider Z, D’Souza R Non-contraceptive benefi ts and risks of contraception. Best Pract Res Clin Obstet Gynaecol. 2009;23(2):249–62. doi: 10.1016/j.bpobgyn.2008.12.003.

Seracchioli R, Mabrouk M, Manuzzi L, Vicenzi C, Frasca C, Elmakky A et al. Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis. Hum Reprod. 2009;24(11):2729–35. doi: 10.1093/humrep/dep259.

Vercellini P, Pietropaolo G, De Giorgi O, Pasin R, Chiodini A, Crosignani PG Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate. Fertil Steril. 2005;84(5):1375–87. doi: 10.1016/j.fertnstert.2005.03.083.

Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Crosignani PG Endometriosis: current therapies and new pharmacological developments. Drugs. 2009;69(6):649–75. doi: 10.2165/00003495-200969060-00002.

Maia H, Jr., Casoy J, Correia T, Freitas L, Pimentel K, Athayde C Eff ect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis. Gynecol Endocrinol. 2006;22(10):547–51. doi: 10.1080/09513590601005375.

Ross RK, Pike MC, Vessey MP, Bull D, Yeates D, Casagrande JT Risk factors for uterine fi broids: reduced risk associated with oral contraceptives. Br Med J (Clin Res Ed). 1986;293(6543):359–62. doi: 10.1136/bmj.293.6543.359.

Chiaff arino F, Parazzini F, La Vecchia C, Marsico S, Surace M, Ricci E Use of oral contraceptives and uterine fi broids: results from a case-control study. Br J Obstet Gynaecol. 1999;106(8):857–60. doi: 10.1111/j.1471-0528.1999.tb08409.x.

Burkman RT Oral contraceptives: current status. Clin Obstet Gynecol. 2001;44(1):62–72. doi: 10.1097/00003081-200103000-00010.

Spector TD, Hochberg MC The protective eff ect of the oral contraceptive pill on rheumatoid arthritis: an overview of the analytic epidemiological studies using meta-analysis. J Clin Epidemiol.1990;43(11):1221–30. doi: 10.1016/0895-4356(90)90023-I.

Jorgensen C, Picot MC, Bologna C, Sany J Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis. Ann Rheum Dis. 1996;55(2):94–8. doi: 10.1136/ard.55.2.94.

Drossaers-Bakker KW, Zwinderman AH, van Zeben D, Breedveld FC, Hazes JM Pregnancy and oral contraceptive use do not signifi cantly infl uence outcome in long term rheumatoid arthritis. Ann Rheum Dis. 2002;61(5):405–8. doi: 10.1136/ard.61.5.405.

Holmqvist ST, Hammar M, Lindblom AM, Brynhirdsen J Age at onset of Multiple sclerosis is correlated to use of combined oral hormonal contraceptives and child birth before diagnosis. Fert Steril.2010;94:2835–7. doi: 10.1016/j.fertnstert.2010.06.045.

Kuhl H, Birkhauser M, Mueck A, Neulen J, Thaler C, Kiesel L et al. [Long-cycle treatment in oral contraception]. Ther Umsch. 2009;66(2):101–8. doi: 10.1024/0040-5930.66.2.101.

Sulak P, Willis S, Kuehl T, Coff ee A, Clark J Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache. 2007;47(1):27–37. doi: 10.1111/j.1526-4610.2007.00650.x.

Williams JK Noncontraceptive benefi ts of oral contraceptive use: an evidence-based approach. Int J Fertil Womens Med. 2000;45(3):241–7.

La FM, Ledger WL, Davidson JW, Howard DM, Jones GL The eff ects of a third generation combined oral contraceptive pill on the classical singing voice. J Voice. 2007;21(6):754–61. doi: 10.1016/j.jvoice.2006.05.009.

Mandhane PJ, Hanna SE, Inman MD, Duncan JM, Greene JM, Wang HY et al. Changes in exhaled nitric oxide related to estrogen and progesterone during the menstrual cycle. Chest.2009;136(5):1301–7. doi: 10.1378/chest.09-0604.

Royal College of General Practitioners’ Oral Contraception Study. Eff ect on hypertension and benign breast disease of progestogen component in combined oral contraceptives. Lancet. 1977;1:624.

Brinton LA, Vessey MP, Flavel R, Yeates D Risk factors for benign breast disease. Am J Epidemiol.1981;113(3):203–14.

Siskind V, Green A, Bain C, Purdie D Beyond ovulation: oral contraceptives and epithelial ovarian cancer. Epidemiology. 2000;11(2):106–10. doi: 10.1097/00001648-200003000-00005.

The reduction in risk of ovarian cancer associated with oralcontraceptive use. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. N Engl J Med. 1987;316(11):650–5. doi: 10.1056/NEJM198703123161102.

Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner’s oral contraception study.BMJ. 2007;335(7621):651. doi: 10.1136/bmj.39289.649410.55.

World Health Organization, IARC IARC Monographs on the evaluation of carcinogenic risk to humans. Hormonal contraception and postmenopausal hormonal therapy. Lyon: 1999.

Tworoger SS, Fairfi eld KM, Colditz GA, Rosner BA, Hankinson SE Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol.2007;166(8):894–901. doi: 10.1093/aje/kwm157.

Vessey M, Painter R Oral contraceptive use and cancer. Findings in a large cohort study, 1968-2004. Br J Cancer. 2006;95(3):385–9. doi: 10.1038/sj.bjc.6603260.

Beral V, Doll R, Hermon C, Peto R, Reeves G Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet.2008;371(9609):303–14. doi: 10.1016/S0140-6736(08)60167-1.

Schlesselman JJ Net eff ect of oral contraceptive use on the risk of cancer in women in the United States. Obstet Gynecol. 1995;85(5 Pt 1):793–801. doi: 10.1016/0029-7844(95)00022-J.

McLaughlin JR, Risch HA, Lubinski J, Moller P, Ghadirian P, Lynch H et al. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet Oncol. 2007;8(1):26–34. doi: 10.1016/S1470-2045(06)70983-4.

Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis.Am J Obstet Gynecol. 2004;191(3):733–40. doi: 10.1016/j.ajog.2004.03.035.

Noncontraceptive health benefi ts of combined oral contraception Hum Reprod Update.2005;11(5):513–25. doi: 10.1093/humupd/dmi019.

Weiderpass E, Adami HO, Baron JA, Magnusson C, Lindgren A, Persson I Use of oral contraceptives and endometrial cancer risk (Sweden). Cancer Causes Control. 1999;10(4):277–84. doi: 10.1023/A:1008945721786.

Xu WH, Xiang YB, Ruan ZX, Zheng W, Cheng JR, Dai Q et al. Menstrual and reproductive factors and endometrial cancer risk: Results from a population-based case-control study in urban Shanghai. Int J Cancer. 2004;108(4):613–9. doi: 10.1002/ijc.11598.

Fernandez E, La Vecchia C, Balducci A, Chatenoud L, Franceschi S, Negri E Oral contraceptives and colorectal cancer risk: a meta-analysis. Br J Cancer. 2001;84(5):722–7. doi: 10.1054/bjoc.2000.1622.

Furner SE, Davis FG, Nelson RL, Haenszel W A case-control study of large bowel cancer and hormone exposure in women. Cancer Res. 1989;49(17):4936–40.

Schindler AE. Long-term use of progestogens: colon adenoma and colon carcinoma. Gynecol Endocrinol. 2007;23:42–4. doi: 10.1080/09513590701584899.

Weiss NS, Daling JR, Chow WH Incidence of cancer of the large bowel in women in relation to reproductive and hormonal factors. J Natl Cancer Inst. 1981;67(1):57–60.

Britt K, Short R The plight of nuns: hazards of nulliparity. Lancet. 2012;379(9834):2322–3. doi: 10.1016/S0140-6736(11)61746-7.





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