Is spotting on mixed hormone birth control normal?
Pleconaril
The U.S. Food and Drug Administration rejected pleconaril in 2002 due to the side effects. The most commonly reported side effects were mild to moderate headache, diarrhea, and nausea. Some women were having symptoms of spotting in between periods. Menstrual irregularities were reported by 3.5% of the 320 pleconaril treated women using oral contraceptives and by none of the 291 placebo treated women. In the clinical trial two women became pregnant due to the drug interfering with hormonal birth control. Other patients have described painful nasal inflammation. Another side effect of the Pleconaril drug trials was activation of cytochrome P-450 3A enzymes.
Gynecomastia
Chronic exposure (or "in utero" in the case of children with abnormal gynecomastia at birth) to low doses of endocrine disruptors, which mimic estrogen, and/or products that have hormonal and/or toxic impacts on the thyroid or testicles may also have an effect. In 2010 Dumas et al. analyzed the plasma levels of two phthalates, DEHP and its metabolite MEHP, in 39 adolescents with gynecomastia and 20 control subjects without it. DEHP was detected in all samples and its metabolite MEHP as well except in a control sample. A positive correlation existed with blood plasma concentrations of DEHP and MEHP; significantly higher concentrations were found in adolescents who had gynecomastia, with no apparent link to the levels of FSH, LH, SHBG, total and free testosterone hormone. This work was subsequently confirmed by a study on a larger number of adolescents.