There is also often fatigue, lethargy, exhaustion, and depression with a sense of hopelessness and helplessness. All too often men change their jobs or their women – anything to ease the malaise they feel, usually with little relief, and sometimes things are made much worse because of the additional stress these changes bring. Physically there is often stiffness and pain in the muscles and joints, or symptoms of gout, and a rapidly deteriorating level of fitness. There may also be signs of accelerated ageing of the heart and circulation.
After the Kefauver Harris Amendment was passed in 1962, the . FDA began the DESI review process to ensure the safety and efficacy of drugs approved under the more lenient pre-1962 standards, including Dianabol.  In 1965, the FDA pressured CIBA to further document its legitimate medical uses, and re-approved the drug for treating post-menopausal osteoporosis and pituitary-deficient dwarfism .  After CIBA's patent exclusivity period lapsed, other manufacturers began to market generic metandienone in the .
Disturbances in the endocrine system that lead to an increase in the ratio of estrogens/androgens are thought to be responsible for the development of gynecomastia. This may occur even if the levels of estrogens and androgens are both appropriate but the ratio is altered. Diagnosis is based on symptoms. Conservative management of gynecomastia is often appropriate as the condition commonly resolves on its own. Medical treatment of gynecomastia that has persisted beyond two years is often ineffective. Medications such as aromatase inhibitorshave been found to be effective in rare cases of gynecomastia from disorders such as aromatase excess syndromeor Peutz–Jeghers syndrome, but surgical removal of the excess tissue is usually required.