Can Depo-Provera (medroxyprogesterone acetate) cause tumors?

Depo-Provera and Tumor Risk

Depo-Provera (medroxyprogesterone acetate) does not increase the overall risk of most tumors and actually provides a protective effect against endometrial cancer, though there may be a slightly increased risk of breast cancer in recent users under 35 years of age and it should be avoided in patients with certain neuro tumors.

Breast Cancer Risk

• Long-term surveillance of Depo-Provera users found slight or no increased overall risk of breast cancer 1
• The relative risk (RR) of breast cancer for women who had ever used Depo-Provera is 1.1 (95% confidence interval 0.97 to 1.4), indicating no significant overall increase in risk 1, 2
• However, women who started using Depo-Provera within the previous 5 years had an estimated RR of 2.0 (95% CI 1.5 to 2.8), suggesting a possible temporary increase in risk for recent users 1, 2
• Women under 35 years of age whose first exposure was within the previous 4 years showed an increased RR of 2.19 (95% CI 1.23 to 3.89) 1
• The increased risk in recent users may be due to enhanced detection of existing tumors rather than causing new tumors 2
• Women who had used Depo-Provera more than 5 years previously had no increase in risk regardless of duration of use 2, 3

Protective Effects Against Certain Cancers

• Depo-Provera provides a prolonged, protective effect by reducing the risk of endometrial cancer 1, 4
• Use of Depo-Provera is associated with an 80% risk reduction of endometrial adenocarcinoma, which is even greater protection than that provided by oral contraceptives 4

Other Gynecologic Cancers

• No overall increased risk of ovarian, liver, or cervical cancer has been found in Depo-Provera users 1, 4
• A statistically insignificant increase in invasive squamous-cell cervical cancer has been noted in women first exposed before age 35 (RR 1.22 to 1.28), but the overall relative rate was 1.11 (95% CI 0.96 to 1.29), which is not significant 1

Neurological Tumors

• Depo-Provera should generally be avoided in individuals with a history of neurofibromas or meningiomas due to evidence suggesting it may stimulate tumor growth 5
• Expression of progesterone receptors has been found in 75% of neurofibromas, making them potentially responsive to hormonal stimulation 5
• A survey of women with Neurofibromatosis Type 1 found that 3% of patients who received depot contraceptives containing high doses of synthetic progesterone reported significant tumor growth 5

Monitoring Recommendations

• Regular monitoring for changes in existing tumors or development of new tumors is essential for patients already using Depo-Provera 5
• Any neurological symptoms such as persistent headaches, vision changes, or seizures should prompt evaluation regardless of contraceptive method 6
• The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, pulmonary embolism, cerebrovascular disorders, and retinal thrombosis) 1

Alternative Contraceptive Options

• For patients with a history of neuro tumors, alternative contraceptive methods should be discussed, particularly for those with documented progesterone receptor-positive tumors 5
• Intrauterine devices (IUDs) are well-tolerated by 83.3% of patients with neurofibromatosis, and the progesterone-eluting IUD could be beneficial at lower doses than injectable forms 5
• Oral contraceptives do not seem to stimulate the growth of neurofibromas in most patients with neurofibromatosis 5

Clinical Considerations

• The prevention of unintended pregnancy is important, and the benefits of contraception may outweigh theoretical concerns in many cases 5
• The CDC classifies Depo-Provera as category 2 (benefits generally outweigh risks) for most women, making it an important contraceptive option, particularly for women who cannot use estrogen-containing contraceptives 6
• For patients with epilepsy related to brain tumors who require contraception, drug interactions between anticonvulsants and hormonal contraceptives should be considered 5

In summary, while Depo-Provera does not increase overall cancer risk for most women and provides protection against endometrial cancer, caution should be exercised in patients with a history of neuro tumors and in young women who may be at slightly increased risk of breast cancer during active use.