Effects of cyproheptadine clorhydrate ,a serotonin receptor antagonist ,on endocrine parameters in weight-loss related amenorrhea

Abstract

The aim of the study was to evaluate the possible interactions and/or modulations of the serotoninergic system on hormonal parameters and the reproductive axis in amenorrheic subjects. Hypogonadotropic, underweight, amenorrheic patients (n = 8) were studied before and during cyproheptadine clorhydrate administration (4 mg/day for 3 months). A pulsatility study (4 hours, sampling every 10 minutes) and a naloxone test were performed before and after 4 and 12 weeks of treatment. Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), estradiol, thryoid-stimulating hormone (TSH), free tri-iodothyronine (fT3), free thyroxine (fT4) and total tri-iodothyonine (total T3), insulin-like growth factor-I (IGF-I) concentrations were determined. Pulse detection analysis was performed using the DETECT program. Serotoninergic receptor blockade affected neither the naloxone-inducted LH response nor the gonadotropin pulsatile parameters. Body mass index (BMI) did not vary; conversely, integrated mean gonadotropins, GH and fT3 concentrations increased during the treatment. In conclusion, cyproheptadine administration affects some of the abnormal endocrine parameters of underweight amenorrheic subjects with no modulation of the opioidergic system. It is likely that the gonadotropin and the fT3 increases take place owing to a change in the metabolic signals modulating hypothalamic function and/or an increased energy availability. Our study suggests a specific central effect of cyproheptadine on the serotonergic pathway controlling food intake at the hypothalamic level.

Short-Term Cyproheptadine Therapy in Underweight Children: Effects on Growth and Serum Insulin-like Growth Factor-I

“…In addition, previous studies have shown that serum IGF-I is a sensitive index of nutritional repletion in malnourished children 23 increment of growth rate in the cyproheptadine group accompanied an increase in serum IGF-I concentration. By contrast, an increased 4-hour integrated mean GH concentration during 3 months cyproheptadine therapy in underweight amenorrheic patients was demonstrated 25 . Given the evidence of blunting of the GH response during GH provocative testing in cyproheptadinetreated individuals 13 " 15 , cyproheptadine therapy may therefore have a detrimental effect, if any, on 24hour integrated GH secretion, and consequently may attenuate IGF-I secretion.…”

Estriol administration modulates luteinizing hormone secretion in women with functional hypothalamic amenorrhea

“…All these situations lead to or amplify the disruption of the hypothalamus-pituitary activity controlling ovarian function (1,7,(23)(24)(25). In the last decade, various therapeutic strategies have been proposed to recover the reproductive function of patients affected by FHA who are trying to avoid the use of oral contraceptives, such as naltrexone chlorohydrate, an opioid receptor antagonist (26)(27)(28), cyproheptadine, a serotonin receptor antagonist, (29) or acetyl-L-carnitine (30).…”

Cancer cachexia—pathophysiology and management

“…Cyproheptadine also appeared to stimulate appetite and decrease diarrhea in patients with advanced carcinoid tumors [113]. Studies on the effects of cyproheptadine in progressive weight loss in patients with cancer or other causes of cachexia suggest that cyproheptadine has a beneficial effect on appetite stimulation but only slight effects on weight gain [110, 114, 115]. 5-hytroxytryptamine type 3 (5HT3) receptor antagonists, such as ondansetron and granisetron, have entered widespread clinical use as antiemetics for cancer chemotherapy [99].…”