Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1ß, IL-6, IL-10 and TNF-α.

Oxandrolone (OXA) is an androgen and anabolic steroid (AAS) that is used to reverse weight loss associated with some medical conditions. One of the side effects of OXA is its potential to induce depressive symptoms. Growing evidence suggested that neuroinflammation and cytokines play crucial roles in sickness behavioral and associated mood disturbances. Previous studies showed that metformin attenuated neuroinflammation. This study investigated the potential protective role of metformin against OXA-induced depression-like behavior and neuroinflammation. Twenty- four Wistar male rats were randomly grouped into four groups: the control group (Control) received only vehicle; the oxandrolone group (OXA) received oxandrolone (0.28 mg/kg, i.p); the metformin group (MET) received metformin (100 mg/kg, i.p); and the oxandrolone / metformin group (OXA + MET) received both oxandrolone (0.28 mg/kg, i.p) and metformin (100 mg/kg, i.p). These treatments were administered for fourteen consecutive days. Behavioral tests to measure depression-like behavior were conducted before and after treatments. qRT-PCR was used to measure the relative expression of proinflammatory and anti-inflammatory cytokines in the hippocampus and hypothalamus. The results showed that oxandrolone induced depression-like behavior and dysregulated pro-/anti-inflammatory cytokines, while metformin attenuated these effects. These findings suggest that metformin is a potential treatment to reverse the depressive effects induced by oxandrolone that involve neuroinflammatory effects.

9 clinical cases of nonhealing pressure ulcers in patients with spinal cord injury treated with an anabolic agent: a therapeutic trial.

Anabolic steroid agents may potentially promote wound healing in individuals with spinal cord injury who have long-standing wounds. Nine patients hospitalized on the Spinal Cord Injury Service of the VA Medical Center, Bronx, NY, received treatment with an anabolic agent and amino acid supplement. Selection of patients was based on having at least 1 of the following criteria: (1) nonhealing pressure ulcer of at least 2 months' duration with no change or worsening status, and/or (2) full-thickness pressure ulcer through fascia into muscle, tendon, or bone. Previous and current pressure ulcer histories were determined by review of the hospital records when available and/or self-reporting by the patient. Eight of 9 patients had nonhealing wounds of 2 months' to 5 years' duration. One patient was included because of having a large, full-thickness pressure ulcer of reportedly 2 weeks' duration. Except for 1 Stage III pressure ulcer, all others had Stage IV pressure ulcers.Three patients had documented weight loss (>10% of total body weight), 3 had no recent weight loss, and 3 refused to be weighed. Patients were treated from 1 to 12 months with oxandrolone (20 mg/day) and glutamine (20 g/day). Eight of 9 patients completely healed: 3 after 3 months, 2 after 4 months, 1 after 6 months, and 2 after 12 months of treatment. One patient was discharged against medical advice after 1 month of treatment with a healing wound and was lost to follow-up. Although clinical case studies have limited usefulness for determining effectiveness of drug therapy on wound healing, these initial observations of successful treatment with an anabolic agent and amino acid supplement have been encouraging.

Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis.

In 29 women with postmenopausal osteoporosis, the proportion of total bone surface undergoing resorption or formation was evaluated by microradiography of iliac crest biopsy samples before and after short-term (2(1/2)-4 months) and long-term (26-42 months for estrogen and 9-15 months for anabolic hormone) treatment. After estrogen administration, values for bone-resorbing surfaces decreased, although less prominently after long-term than after short-term therapy. The magnitude of this decrease was positively correlated with the pretreatment value for bone-resorbing surfaces (P < 0.001). When the pretreatment value for bone-resorbing surfaces was used as a covariable, estrogen and anabolic hormone appeared to be equally effective. For bone-forming surfaces, short-term therapy with either hormone had no effect but long-term therapy significantly decreased the values. Serum immunoreactive parathyroid hormone (IPTH) increased significantly after estrogen therapy; the change in IPTH was inversely related to the change in serum calcium (P < 0.001, sign test). We conclude that the primary effect of sex hormones in postmenopausal osteoporosis is to decrease the increased level of bone resorption, perhaps by decreasing the responsiveness of bone to endogenous parathyroid hormone. However, this favorable effect, at least in part, is negated after long-term treatment by a secondary decrease in bone formation. Our data are consistent with the concept that the maximal benefit that can be derived from sex hormone therapy in postmenopausal osteoporosis is arrest or slowing of the progession of bone loss.