Variation in breast cancer risk appears to be tied to the progestin type, and researchers have suggested avoiding desogestrel for some patients.
Levonorgestrel-based contraceptives were associated lower risk of breast cancer compared to products with desogestrel, according to a large Swedish study.
While ever using any hormonal contraceptive was linked to about a 25% higher risk of breast cancer, or one extra breast cancer case for every about 7700 women, not all formulations appeared equal.
Combined and progestin-only contraceptives were associated with a roughly 20% higher risk of developing breast cancer, as were implants containing etonogestrel (the active metabolite of desogestrel).
Levonorgestrel-containing combined pills and 52 mg levonorgestrel IUS were associated with an almost 10% increase in risk, and progestin-only lynestrenol was associated with a 13% increased risk.
However, duration of use was key.
For short-term use, there was not an association between combined contraceptives and increased risk, but there was for progestin-only products.
Across all hormonal methods, less than one year of use was associated with an 11% increase in risk; one to five years, a 21% increase; and five to 10 years, a 34% increase.
For five to 10 years of use, consistently higher risks were seen for all desogestrel-containing formulations: progestin-only pills (around 50% increase), combined pills (nearly 50% increase), and the etonogestrel implant (around 45%).
Levonorgestrel-containing combined pills and 52 mg levonorgestrel IUS reached a 20% increase for this length of use.
Cumulative absolute risk rose more steeply as age increased.
Researchers found no meaningful increase in risk for medroxyprogesterone acetate injections, etonogestrel vaginal ring and combined oral contraceptives containing drospirenone.
The study included more than two million girls and premenopausal women aged 13 to 49 years who were followed up from 2006 to 2019 – roughly 21 million person-years.
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They had no history of breast cancer, ovarian cancer, cervical cancer, uterine cancer, bilateral oophorectomy or infertility treatment.
The median age was 45 years, and more than 16,000 cases of breast cancer occurred.
The median duration of use was longer for progestin-only than for combined contraceptives, potentially contributing to the higher HR, researchers noted.
Researchers noted that the findings were supported by underlying biological mechanisms.
Progestins stimulate breast cancer cell proliferation mainly through binding to progesterone receptors. They also bind to androgen receptors, whose signalling has antiproliferative and proapoptotic effects.
Desogestrel shows considerably lower binding to androgen receptorscompared to levonorgestrel, potentially providing less of this protective androgen-receptor activity.
The researchers concluded that individuals at risk of breast cancer may benefit from avoiding desogestrel-containing hormonal contraceptives, particularly in progestin-only formulations.
