Is Fatigue a Side Effect of Yaz?
Yes, fatigue is a recognized side effect of Yaz (drospirenone 3 mg/ethinyl estradiol 20 µg), occurring in 1-4.2% of users depending on the indication, though it typically resolves within the first 2-3 cycles of therapy. 1, 2
Incidence and Clinical Context
The frequency of fatigue varies by indication and study population:
- In PMDD trials, fatigue occurred in 4.2% of users and was significant enough to cause discontinuation in 1.8% of participants 2
- In contraception and acne trials, fatigue was reported at a lower rate of approximately 1-2% 3, 1
- The majority of common side effects, including fatigue, resolve spontaneously within the first 2-3 cycles and rarely necessitate discontinuation 1
Comparative Context with Other Medications
When considering the broader context of hormonal therapies:
- Spironolactone (often used concomitantly with COCs for acne) lists fatigue as a common side effect, which may confound attribution when both medications are used together 3
- The antimineralocorticoid properties of drospirenone—which distinguish it from other progestins—may theoretically contribute to fatigue through effects on fluid balance and electrolytes, though this mechanism has not been definitively established 1
Recent Evidence on Health Status
- A 2021 study found that long-term users of DRSP/EE formulations reported moderate to severe fatigue and more health-related symptoms compared to non-users 4
- This same study demonstrated altered biotransformation activity (reduced CYP1A2, increased phase II conjugation) and elevated oxidative stress markers in COC users, which may mechanistically explain persistent fatigue 4
Clinical Management Approach
Reassure patients that fatigue typically diminishes after 2-3 cycles of use 1. If fatigue persists beyond this timeframe:
- Verify medication adherence and timing of administration 1
- Consider whether the patient is taking concomitant spironolactone, which independently causes fatigue 3
- Evaluate for alternative causes of fatigue (anemia, thyroid dysfunction, sleep disorders) 4
- If fatigue remains severe and impacts quality of life after 3 cycles, consider switching to a levonorgestrel-containing formulation, which has a different metabolic profile 1, 5
Important Caveats
- Fatigue is not among the most common side effects of Yaz—menstrual irregularities (4.7-24.9%), nausea (4.2-15.8%), headache (6.7-13%), and breast tenderness (4-10.5%) occur more frequently 1, 2
- The 1-4% incidence rate means most women will not experience fatigue as a side effect 3, 1, 2
- Fatigue severe enough to warrant discontinuation is uncommon (1.8% in PMDD trials) 2