It is well known that combination contraceptives (containing estrogens AND progestins) increase the risk for venous thromboembolism (VTE). Relatively few data, however, have been published on progestin-only contraceptives, so that until recently it was not clear whether they increase the risk for venous thromboembolism (VTE) or not.
The words “progestin” and “progestagen” are synonyms. They are a class name for several different types of individual hormone-preparations (such as progesterone, medroxyprogesterone, norgestrel, norethindrone, etc.). The term “mini-pill” is sometimes used for progestin-only pills; the expression should not be confused with “low-dose estrogen combined contraceptives”.
Types of Progestin-Only Contraceptives
- Oral pills (Micronor®, Ovrette®, NOR-QD®, Camila®, Jolivette®, Errin®, Nora-BE®).
- Depo-Provera® intramuscular injection (= depot medroxy-progesterone)
- Implanon® rod, subcutaenous
- Mirena® IUD – www.mirena-us.com
The Mirena® IUD and the Skyla® IUD release progestins, but only low levels are absorbed into the blood stream. They may, therefore, be particularly suitable contraceptive methods in individuals with a history of thrombosis or thrombophilia.
The Published Studies
Only a few studies investigating the risk for VTE with progestin-only contraceptives exist [1-6,8,9,11]. A recent summary of the first of these 5 published studies concludes that (a) the risk of VTE with progestin-only contraceptives is poorly investigated and (b) that there may be a slightly elevated VTE risk [ref 7]. Since then a study has shown a statistically significant 3-4 fold increased risk of VTE with injectable progestin-only contraceptives, but no increased risk with progestin-releasing IUD [ref 8]. An additional study also suggests that progestins-only contraceptives may be associated with a higher risk for VTE [ref 9]. While a very recent review article [ref 10] has concluded that “progestogen-only contraceptives are not associated with an increased risk of VTE”, the article did not take reference to the two most recently published studies [ref 8,9]; its conclusion is, therefore, not up-to-date.
Finally, it is not known whether progestin-only contraceptives are safe in women who (a) have had a previous clot or (b) have a thrombophilia or family history of VTE. I am aware of only one published study of women with thrombosis or with a family history of thrombosis who took a progestin-only pill [ref 9]. This study showed that there was no increased risk of thrombosis with the progestin-only pill. However, the progestin pill evaluated in the study is not available in the U.S.
For clinical practice purposes, my conclusions from these somewhat limited progestin-only contraceptive data are:
- Progestin-releasing IUDs (e.g. Mirena®, Skyla®) appear to not increase the risk for VTE.
- Oral progestin-only contraceptives (minipill) may lead to an increased risk of VTE, but this is not certain. However, the risk appears to be more clearly increased if additional VTE risk factors are present (e.g. obesity, immobility, surgery).
- Injectable progestins appear to lead to an increased risk of VTE.
The advice I presently give to women with known thrombophilia or with a history of DVT, particularly when additional VTE risk factors (e.g. obesity) are present: I advise against the use of injectable and oral progestin-only contraceptives. I state that a progestin-releasing IUD (Mirena® or Skyla® IUD) is a good and likely safe contraceptive choice, if a hormonal method is desired.
- Farmer RDT et al. The risk of venous thromboembolism associated with low oestrogen oral contraceptives. J Obstet Gynecol 1995;15:195-200.
- World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Contraception 1998;57:315-324.
- Vasilakis C et al.: Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet 1999;354:1610-1611.
- Heinemann LA et al. Oral progestogen-only contraceptives and cardiovascular risk. Eur J Contracept Reprod Health Care 1999;4:67-73.
- Lidegaard Ø et al. Oral contraceptives and venous thromboembolism: a five year national case-control study. Contraception 2002;65:187-196.
- Lidegaard Ø et al. Hormonal contraception and risk of venous thromboembolism: natinal follow-up study. Br Med J 2009;339:b2890.
- Bergendal A et al. Limited knowledge on progestogen-only contraception and risk of venous thromboembolism. Acta Obstetrica et Gynecologica 2009;88:261-266.
- van Hylckama-Vlieg A et al. The risk of deep vein thrombosis associated with injectable depot-medtoxyprogesterone acetate contraceptives or a levonorgestrel intrauterine device. Arterioscler Thromb Vasc Biol 2010(Nov);30:2297-2230.
- Barsoum MK et al. Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study. Thromb Res 2010;126:373-378.
- Hannaford PC. Epidemiology of the contraceptive pill and venous thromboembolism. Thromb Res 2011;127(suppl 3):S30-S34.
- Conard J et al: Progestogen-only contraception in women at high risk of venous thromboembolism. Contraception 2004;70:437-441.
For non-Health Care Professionals
This same educational blog, written for patients and other non-health care professionals, is available at http://clotconnect.wordpress.com/2011/02/02/progestin-only-contraceptives-and-blood-clots/
Disclosure: I have no financial conflict of interest relevant to this blog entry.
Last updated: June 3rd, 2013