Fresh evidence confirms links between newer contraceptive pills and higher risk of venous thromboembolism
BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h2422 (Published 26 May 2015) Cite this as: BMJ 2015;350:h2422
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These and previous data show a convincing differential risk of venous thrombo-embolic disease (VTE), depending on the type of synthetic progestogen contained within combined oral contraceptives (COCs). Therefore, unless there are compelling clinical or individual patient-specific reasons, COCs containing these progestogens should no longer be routinely prescribed.
Comparison between different COCs has been made simpler, because all of them (for entirely historic reasons, rather than any hard science or logic) contain the same synthetic oestrogen analog, Ethinyloestradiol (EE). However, this has also led to a crucial variable being missing from the dataset, namely the relative thrombogenicity of different oestrogen analogs, compared with native human 17beta-oestradiol (E2).
Data from the Amsterdam registry of male-to-female trans-sexuals showed a threefold greater risk of cardiovascular death among those receiving EE, compared with E2 (1,2) and data from the London Charing Cross registry found an eightfold greater risk of VTE in trans-women taking conjugated equine estrogens compared with those receiving oral or transdermal E2 (3).
There are therefore highly-compelling reasons to encourage the Pharma industry to develop COCs based on bioidentical E2, rather than synthetic analogs.
1. van Kesteren PJ, Asscheman H, Megens JA, et al. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf ) 1997; 47: 337-342.
2. Asscheman H, Giltay EJ, Megens JA, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 2011; 164: 635-642.
3. Seal LJ, Franklin S, Richards C, et al. Predictive markers for ammoplasty and a comparison of side effect profiles in transwomen taking various hormonal regimens. J Clin Endocrinol Metab 2012; 97: 4422-4428.
Competing interests: No competing interests
Re: Fresh evidence confirms links between newer contraceptive pills and higher risk of venous thromboembolism
Professor Susan Jick hopes Vinogradova‘s confirmation, that newer oral contraceptives increase the risk of venous thromboembolism 4 to 5 times compared with a 2.5 times for older contraceptives, provides important guidance for the safe prescribing of oral contraceptives.1,2
Unfortunately a range of serious adverse inevitably effects result from use of contraceptive progestogens. All act predominantly like progesterone but may also have androgenic or oestrogenic activity. Changing strengths and doses of progestogens and oestrogens merely switches which adverse effects are most likely.3
Increasing progestogen and oestrogen doses or potencies changed effects from irregular bleeding and escape ovulations,4 to venous changes and venous thromboembolism,5 to arterial thickening and vascular diseases including migraine, strokes and heart attacks,6 and, to increased monoamine oxidase activity and depressive mood changes.7
Three times more takers under age 30 years died than never takers in the Royal College of General Practitioners oral contraception study. Ever takers had higher rates of violent death than never takers. Also the risk of CNS or pituitary tumours increased significantly (5.51) with less than 4 year of use.8 Currently, antidepressant use is increasing most in the youngest women taking progestogen only contraceptives.9 Cancer is the commonest cause of death in ever users and breast cancer is the commonest cancer in women of hormone-taking ages. Metastatic breast cancer is increasing most in the youngest women.10
Unfortunately, changing oral contraceptives to avoid doubling an increased risk of venous thromboembolism may not lead to safer hormonal contraception overall.
1 Jick SS. Fresh evidence confirms links between newer contraceptive pills and higher risk of venous thromboembolism. BMJ 2015;350:h2422
2 Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2015;350:h2135,7
3 Changing oral contraceptives. BMJ 1969;4:789-91 & Today's Drugs
4 Grant ECG. Hormone balance of oral contraceptives. BJOG 1967;74:908-18.
5 Grant ECG. Relation between headaches from oral contraceptives and development of endometrial arterioles. BMJ 1968;3:402-5.
6 Grant ECG, Pryce Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. BMJ 1968;3:777-80.
7 Grant ECG. Venous effects of oral contraceptives. BMJ 1969;2:73-7.
8 Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners' Oral Contraception Study. BMJ 2010; 340: c927
9 Johnson RH, Chein FL, Bleyer A. Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA 2013;309(8):800-805.
10 Wiréhn AB, Foldemo A, Josefsson A, Lindberg M. Use of hormonal contraceptives in relation to antidepressant therapy: A nationwide population-based study. Eur J Contracept Reprod Health Care 2010;15:41-7.
Competing interests: No competing interests