Can Estriol Cause Fever?
Estriol is not known to cause fever as a direct adverse effect, and there is no evidence in the medical literature linking estriol administration to fever in adult female patients.
Evidence Review
Drug-Induced Fever Context
While many medications can cause drug-induced fever through hypersensitivity reactions, estriol is not identified among the drugs associated with this phenomenon. Drug-induced fevers typically occur with a mean lag time of 21 days (median 8 days) after drug initiation and resolve within 1-7 days after discontinuation of the offending agent 1. However, estriol does not appear in the literature as a causative agent for such reactions.
Hormonal Causes of Fever
Endocrine disorders can cause fever, including thyrotoxicosis, thyroiditis, adrenal insufficiency, and pheochromocytoma 2. However, estriol therapy itself is not documented as an endocrinologic cause of fever 2.
Estriol Safety Profile
The available evidence on estriol demonstrates:
Estriol is a weak estrogen with a favorable safety profile when used for menopausal symptoms, vaginal atrophy, and urogenital health 3, 4.
Common side effects of estriol include low rates of uterine bleeding (reported in only one patient out of 20 in one study), but fever is not mentioned as an adverse effect 5.
Estriol appears to be safer than stronger estrogens (estradiol and estrone) with minimal systemic absorption when used vaginally 6, 3.
In clinical trials spanning months to years of estriol use, no fever or pyrexia was reported as a treatment-related adverse event 5, 7.
Clinical Approach to Fever in a Patient Taking Estriol
If fever develops in a patient taking estriol, investigate alternative causes rather than attributing it to the medication:
Rule out infectious causes first, as these are the most common etiology of fever in most clinical settings 1.
Consider other endocrine disorders that can present with fever, including thyroid dysfunction and adrenal insufficiency 2.
Evaluate for other medications the patient may be taking that are more commonly associated with drug-induced fever 1.
Assess for inflammatory conditions unrelated to estriol therapy 1.
Important Caveat
The distinction between estriol and estradiol is clinically relevant: estradiol is a more potent estrogen that binds more strongly to estrogen receptors and can increase circulating estradiol levels within 2 weeks, particularly with higher doses 8. However, neither estriol nor estradiol are documented to cause fever as a direct pharmacologic effect.