Hormonal contraceptives, depression and blood clots

Hormonal contraception is a widely used and very effective method of birth control, but it is not without risks. For decades, women have reported mood changes when using hormonal contraceptives, including birth control pills and hormonal intrauterine devices (IUDs), and large population studies have found a link with depression. Birth control that contains estrogen can also cause dangerous blood clots, especially in women who carry certain gene variants. This article summarizes the research and explains how knowing your genetic factors can help you and your doctor choose a safer method.

Can hormonal birth control cause depression?

A Danish study followed more than one million women and adolescents aged 15 to 34 for up to 14 years. It compared women who used hormonal contraception with those who did not and looked at who started an antidepressant or was diagnosed with depression. Compared with non-users:

• Women taking combined birth control pills (estrogen and progestin) were 23% more likely to start an antidepressant.
• Women taking progestin-only pills were 34% more likely.
• Women using a hormonal (levonorgestrel) IUD were 40% more likely.
• Women using the vaginal ring were 60% more likely.
• Women using the patch were twice as likely.

The risk was highest in adolescents aged 15 to 19, and it peaked about six months after starting hormonal birth control. A Swedish study of more than 700,000 young women found a similar pattern for the hormonal IUD: a 57% higher risk of depression overall and more than double the risk in adolescents, especially when the IUD was their first hormonal method. A French study found that higher-dose hormonal IUDs were linked to more use of medications for anxiety, sleep and depression than lower-dose ones.

These studies show a link, not proof that birth control causes depression in every woman, and most women who use hormonal contraception do not become depressed. It is still unknown why some women are affected and others are not. If your mood changes after starting or switching birth control, talk to your doctor. Changing to a different method, including a non-hormonal one, is an option.

Can hormonal birth control cause blood clots?

Birth control that contains estrogen, including the combined pill, the patch and the vaginal ring, raises the risk of blood clots in the veins (venous thrombosis). These clots usually form in the legs and can travel to the lungs (pulmonary embolism). Rarely, they form in the veins of the brain. In a large Danish study, about 3 in 10,000 non-users developed a clot each year, compared with about 6 in 10,000 women taking the pill. The risk is highest in the first year of use.

The type of progestin in the pill also matters. Compared with pills containing levonorgestrel, pills containing drospirenone (such as Yasmin and Yaz) had a 64% higher risk of clots, and pills containing desogestrel, gestodene or cyproterone had about 1.8 times the risk.

Progestin-only methods are different. In the same study, progestin-only pills and hormonal IUDs were not linked to a higher risk of blood clots.

Although blood clots are a rare side effect, they can be deadly. In December 2025, a young woman in the UK died from blood clots in her brain caused by the birth control pill.

Which genes raise the risk of blood clots?

Two common gene variants make blood clot more easily:

• Factor V Leiden, a variant in the F5 gene. About 3% to 8% of people of European ancestry carry one copy. It is less common in other populations.
• Prothrombin G20210A, a variant in the F2 gene. About 2% to 3% of people of European ancestry carry it.

Most women do not know whether they carry the genetic variants until they have a stroke or another clotting event. In one study, women who carried Factor V Leiden and took the pill had a more than 30 times higher risk of a clot than non-carriers who did not take it. The risk is also higher for F2 carriers, and it is highest in people who carry two copies or both variants. Among carriers, pills containing levonorgestrel had the lowest risk, while pills containing desogestrel or cyproterone had the highest.

Carriers also have a higher risk with other estrogen and hormone-modifying medications, such as menopausal hormone therapy, tamoxifen and medications that stimulate ovulation for fertility treatment. Smoking, obesity, pregnancy, surgery, long periods without moving and long flights add to the risk.

Which birth control is safer if you carry Factor V Leiden or F2?

Guidelines from the U.S. Centers for Disease Control and Prevention (CDC) advise that people with a known clotting variant should not use birth control that contains estrogen. Safer options include:

• The copper IUD, which contains no hormones.
• Progestin-only methods, such as the hormonal IUD, the implant and the progestin-only pill, which are generally considered acceptable.
• Barrier methods, such as condoms, the diaphragm or the cervical cap.

Because progestin-only methods have also been linked to depression, the right choice depends on your own history. Talk with your doctor about both risks before choosing a method.

Can other medications make birth control less effective?

Yes. The hormones in birth control are broken down in the liver, mainly by the enzyme CYP3A4. Some medications speed up this enzyme and lower hormone levels, which can make the pill, patch, ring or implant fail. Examples include the seizure medications carbamazepine and phenytoin, the antibiotic rifampin and the herbal remedy St. John's wort. If you take one of these, your doctor may recommend a copper IUD, a hormonal IUD or an injection instead. Always tell your doctor and pharmacist about every medication and supplement you take.

How can genetic testing help?

Doctors usually look at family history, age, weight and smoking to decide who is at higher risk of complications from hormonal birth control. Women are rarely offered a simple DNA test to find Factor V Leiden or F2 carriers, even though it could save lives.

A Pillcheck test reports Factor V Leiden (F5) and prothrombin (F2) along with genes that affect how you respond to many other medications, such as CYP3A4, CYP2D6 and CYP2C19. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results and medications and gives you recommendations to discuss with your doctor before you choose a birth control method.

Can genetic testing help if you need treatment for depression?

If your mood does not improve after changing your birth control, treatment for depression may be needed. A Pillcheck test also shows how your genes affect antidepressants and anxiety medications. Pillcheck-guided treatment helps people recover from depression and anxiety sooner and reduces the number of medication trials and dose changes, which can otherwise take many months.

Summary

• Hormonal contraception is very effective, but large studies link it to a higher risk of depression, especially in adolescents and in the first months of use.
• Birth control that contains estrogen raises the risk of blood clots. Progestin-only pills and hormonal IUDs were not linked to a higher clot risk.
• Factor V Leiden and the F2 prothrombin variant greatly increase the risk of clots with estrogen-containing birth control, and most carriers do not know they have them.
• Some medications, such as carbamazepine and rifampin, can make hormonal birth control fail.
• Pharmacogenetic testing, such as Pillcheck, can help you and your doctor choose a safer method and the right medications.

Frequently asked questions

Do all hormonal birth control methods cause blood clots?

No. The higher risk comes mainly from methods that contain estrogen: the combined pill, the patch and the vaginal ring. In large studies, progestin-only pills and hormonal IUDs were not linked to a higher risk of clots.

I carry Factor V Leiden. Can I use birth control?

Yes. Guidelines advise avoiding methods that contain estrogen, but the copper IUD, progestin-only methods and barrier methods are options. Your doctor can help you choose based on your health and history.

Does the hormonal IUD affect mood?

Studies from Denmark and Sweden have linked the hormonal IUD to a higher risk of depression, especially in adolescents. Most users are not affected. If you notice mood changes, talk to your doctor.

Should I stop my birth control if I am worried?

Do not stop without a plan, because an unplanned pregnancy also carries risks, including a higher risk of blood clots. Talk to your doctor or pharmacist about switching to another method.

References

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Stenhammar E, Wikman P, Gemzell Danielsson K, et al. Levonorgestrel intrauterine device and depression: A Swedish register-based cohort study. Int J Psychophysiol. 2023;193:112230.

Roland N, Baricault B, Weill A, et al. Association Between Doses of Levonorgestrel Intrauterine Systems and Subsequent Use of Psychotropic Drugs in France. JAMA. 2023;329(3):257-259.

Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890.

Vandenbroucke JP, Koster T, Briët E, et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994;344(8935):1453-1457.

Khialani D, le Cessie S, Lijfering WM, et al. The joint effect of genetic risk factors and different types of combined oral contraceptives on venous thrombosis risk. Br J Haematol. 2020;191(1):90-97.

Kujovich JL. Factor V Leiden Thrombophilia. GeneReviews. University of Washington, Seattle.

Nguyen AT, Curtis KM, Tepper NK, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2024. MMWR Recomm Rep. 2024;73(4):1-126.