If an androgen-associated adverse reaction occurs, treatment should be interrupted and, after disappearance of the symptoms, be resumed at a lower dosage. Patients with latent or overt cardiac failure, renal dysfunction, hypertension, epilepsy or migraine (or a history of these conditions) should be monitored, since androgens may occasionally induce salt and fluid retention. Androgens should be used cautiously in pre-pubertal boys to avoid premature epiphyseal closure or precocious sexual development. A decrease in protein bound iodine (PBI) may occur,but this has no clinical significance. Treatment of male patients over the age of approximately 50 years with androgens should be preceded by a thorough examination of prostate and baseline measurement of prostate-specific antigen serum concentration.
Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid , found naturally in valerian .  Valproic acid is a carboxylic acid , a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol -induced convulsions in laboratory rats .  It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.  Valproic acid has also been used for migraine prophylaxis and bipolar disorder.