Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women.
Level 3 - non-randomized controlled study
Retrospective non-randomized comparative cohort study based on medical records.
PubMed 33973545 · doi:10.1097/GME.0000000000001782
What was done
Medical records were reviewed for 539 postmenopausal women receiving either compounded pellet hormonal therapy (PHT, n = 384) or FDA-approved hormonal therapy (FHT, n = 155). Demographics, indications for hormone therapy, duration of treatment, side effects, serum estradiol (E2) and total testosterone (T) levels, and follow-up lab testing frequency were compared between groups.
What was found
Overall side effects occurred in 57.6% (221/384) of PHT patients compared with 14.8% (23/155) of FHT patients (OR 8.0, 95% CI 4.5–14.2, P < 0.00001). Among women with an intact uterus, abnormal uterine bleeding occurred in 55.3% (136/246) on PHT versus 15.2% (12/79) on FHT (OR 7.9, 95% CI 3.6–17.0, P < 0.0001), and hysterectomy was performed in 20.3% (50/246) on PHT versus 6.3% (5/79) on FHT (OR 3.2, 95% CI 1.1–9.3, P = 0.036). Mean peak serum E2 was significantly higher with PHT (237.70 vs 93.45 pg/mL, P < 0.00001; 4 women > 1,000 pg/mL), as was mean peak T (194.04 vs 15.59 ng/dL, P < 0.00001; 9 women > 400 ng/dL).
Why it matters
This study provides comparative clinical evidence that compounded hormone pellets lead to supraphysiologic hormone levels and substantially higher rates of adverse bleeding events and hysterectomies than FDA-approved formulations.
Limits
The study is a retrospective chart review, making it susceptible to selection bias, non-standardized monitoring intervals, and residual confounding. The abstract does not detail baseline demographic comparability, specific dosing regimens, or long-term clinical endpoints such as cardiovascular disease or breast cancer.
Cited by
- supports Compounded hormone pellets can raise female testosterone levels to male ranges around 500 ng/dL, leading to aromatization and high estrogen levels.