Reduced incidence of ovarian cancer . . . and other storiesBMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i5227 (Published 06 October 2016) Cite this as: BMJ 2016;355:i5227
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It makes no sense to claim that the main reason for the favourable trends in ovarian cancer mortality is the earlier use of oral contraceptives (OCs) in the US, Europe and Australia.1 These countries have higher mortality rates than countries like Japan which resisted the introduction of OCs for longer.
It also makes no sense to believe that OCs prevent ovarian cancer because a meta-analysis of 52 international HRT studies confirmed that using progestogens plus oestrogens or oestrogens alone, for less than 5 years causes ovarian cancer. Risks increase with longer use especially in women starting progestogens and/or oestrogens before age 50 years. However, 58% of ovarian cancer cases had previously used OCs and 42% of cases had started HRT before age 50 years.2 In England and Wales in 1981 there were 6500 oophorectomies and 411 ovarian cancers registered for women under age 45 years (ONS data). Confounding due to high hysterectomy and oophorectomy rates in young women in OCs using countries have led to international epidemiological studies claiming mistakenly that use of progestogens and oestrogens are preventative - but only if used for contraception and not HRT - which is absurd.3
As early as 1967 two 19-nor contraceptive progestins were found to induce ovarian cancer in animals.4 Formation of DNA adducts by cyproterone acetate and some structural analogues in primary cultures of human hepatocytes. DNA adducts, especially containing nickel, increase the risk of mutations and cancer.5 The IARC classified progestogens and oestrogen combinations as highest level Group 1 carcinogens in 2007.
The reduction in progestogen and oestrogen use as HRT has decreased both breast and ovarian cancer mortality the most in countries with more and longer hormone use.
1 Lipschutz A, Inglesias R, Pamosevick V, Salinas S. Ovarian tumours and other ovarian changes induced in mice by two 19-nor contraceptives. Br J Cancer 1967; 21: 153-157.
2 Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk. Individual participant meta-analysis of 52 epidemiological studies. Lancet 2015; February 12.
3 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: 303–14.
4 Werner S1, Kunz S, Beckurts T, Heidecke CD, Wolff T, Schwarz LR. Formation of DNA adducts by cyproterone acetate and some structural analogues in primary cultures of human hepatocytes. Mutat Res 1997 Dec 12;395(2-3):179-87.
5 Hemminki, K. DNA adducts, mutations and cancer. Carcinogenesis,1993; 14:2007–2012.
Competing interests: No competing interests