Serum Estradiol Levels on Seasonique
While taking Seasonique (ethinyl estradiol 30 µg/levonorgestrel 150 µg), serum estradiol levels will be markedly suppressed—typically in the low range or undetectable—because combined oral contraceptives suppress endogenous ovarian estradiol production, but this does not indicate hypogonadism or inadequate estrogenic effects, as the synthetic ethinyl estradiol provides sufficient estrogenic activity throughout the body. 1
Understanding the Hormonal Mechanism
Combined oral contraceptives like Seasonique suppress gonadotropin-releasing hormone (GnRH), which leads to marked reductions in both follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby blocking follicular development and ovulation. 1
This suppression of FSH and LH prevents ovarian estradiol synthesis, resulting in low or undetectable serum estradiol levels when measured by standard laboratory assays. 1
The synthetic ethinyl estradiol in Seasonique is significantly more potent than natural estradiol and provides adequate estrogenic activity to maintain bone health, cardiovascular function, and other estrogen-dependent processes despite the low serum estradiol measurements. 1
Clinical Implications for Interpretation
Do not interpret low serum estradiol levels in patients taking Seasonique as evidence of hypogonadism or estrogen deficiency—this is a normal and expected finding that does not require intervention. 1
The exogenous synthetic estrogen (ethinyl estradiol 30 µg daily for 84 days, followed by 10 µg for 7 days in Seasonique) maintains adequate estrogenic effects throughout the body. 2, 3
Pharmacokinetic studies demonstrate that ethinyl estradiol reaches steady-state concentrations by day 21 and maintains consistent levels through day 84 and day 91 without accumulation. 4
Common Pitfall to Avoid
Avoid ordering serum estradiol levels to "check" hormonal status in patients on combined oral contraceptives—the test will show suppressed levels by design and does not reflect the adequacy of estrogenic effects from the synthetic hormone. 1
If there are concerns about estrogenic effects (such as bone health in long-term users), clinical assessment and other markers are more appropriate than serum estradiol measurement. 1