A 12-day course of an experimental hormone treatment was followed by improvements in sleep, physical restlessness, body weight and eating-disorder symptoms in a 17-year-old girl with long-standing anorexia nervosa, according to a case report from researchers at Rostock University Medical Center in Germany. The treatment used metreleptin, a laboratory-made form of the hormone leptin, outside its approved indications. The patient’s body-mass index rose from 15.4 to 16.2 kilograms per square metre during the treatment period and reached 18.3 two months later. Her compulsive exercise and eating-disorder thoughts also diminished, while objective sleep recordings showed more deep sleep and less wakefulness after initially falling asleep. The authors stress that the report describes only one patient and cannot establish that leptin caused the changes, particularly because she was also receiving intensive inpatient care and gaining weight through standard treatment.
The findings have attracted attention because anorexia nervosa is not simply a disorder of eating behavior. Severe and prolonged energy restriction alters nearly every major physiological system, including the brain circuits that regulate appetite, movement, stress, reproduction and sleep. Insomnia is common in people with anorexia nervosa and can intensify emotional distress and make recovery more difficult. At the same time, some patients develop striking starvation-associated hyperactivity: despite being dangerously underweight, they may feel driven to walk, exercise or remain in motion. Researchers have proposed that these symptoms partly reflect the body’s response to a severe energy deficit. Leptin may be one of the biological signals linking depleted fat stores to changes in behavior and sleep.
Leptin is produced predominantly by adipose tissue and normally provides the brain with information about the amount of energy stored in the body. When fat stores and energy availability decline, circulating leptin concentrations generally fall. The hormone acts on receptors in the hypothalamus, a brain region involved in energy balance and endocrine control, influencing neural populations that include appetite-regulating AgRP neurons and POMC neurons. In ordinary conditions, leptin helps signal that sufficient energy is available, restraining food-seeking pathways and supporting normal reproductive and metabolic function. During starvation, low leptin is interpreted as a warning of energy scarcity. That response may be adaptive in the short term, but in chronic anorexia nervosa it can become entangled with fear of weight gain, compulsive activity, mood symptoms and disrupted circadian physiology.
The German team treated the adolescent with daily injections of recombinant human leptin, known clinically as metreleptin, for 12 days while she remained in hospital and continued to receive usual multidisciplinary care. The intervention was undertaken with the agreement of the patient and her parents, who provided written informed consent for treatment and publication of pseudonymised data. The researchers examined two periods: the first compared measurements taken before dosing with those at the end of day 12, while the second followed the patient from the end of treatment to approximately 60 days later. This distinction was important because any rapid biological response to leptin would be mixed with the slower effects of nutritional rehabilitation and weight restoration. The treatment was reportedly well tolerated, and no side effects were reported during the observation period.
Several changes appeared during the short treatment window. The patient gained weight, and standardized assessments indicated a marked reduction in eating-disorder cognitions and compulsive exercise. Her starvation-associated motor hyperactivity also weakened, suggesting that the treatment may have influenced the physical drive to remain active. These observations are intriguing because they occurred before the patient’s subjective insomnia improved. In other words, her behavior and objective sleep physiology began to change while she did not yet feel that she was sleeping better. The distinction illustrates why sleep research often combines questionnaires with physiological measurements: a person’s perception of insomnia can remain severe even when the architecture of sleep is beginning to shift.
Overnight polysomnography, which records electrical brain activity through electroencephalography alongside other physiological signals, showed an increase in N3 sleep during the 12-day period. N3, often called slow-wave or deep sleep, is the most restorative non-rapid-eye-movement sleep stage and is characterized by high-amplitude, low-frequency delta waves. The recording also showed less wake after sleep onset, a measure of the time spent awake after initially falling asleep. These changes point to improved sleep continuity and a greater proportion of deep sleep, although they do not by themselves prove that leptin restored normal sleep regulation. The study also used a wrist-worn movement sensor to examine activity patterns over time. Non-parametric circadian rhythm analysis later suggested partial normalization of the patient’s daily activity rhythm, including improvements in the regularity and amplitude of her rest–activity cycle.
The more dramatic subjective sleep improvement emerged after the injections had stopped. At the two-month follow-up, the patient reported a marked reduction in insomnia, while her BMI had continued to rise to 18.3. Some broader cognitive-affective symptoms, including depressive features, remained largely unchanged during the initial treatment period and temporarily became more noticeable during the longer follow-up. That pattern underscores how recovery from anorexia nervosa can be uneven: improvements in weight, movement, sleep and eating-disorder thoughts do not necessarily occur at the same pace as improvements in mood or overall cognition. It also makes the causal interpretation especially difficult. Continued nutritional rehabilitation could have improved sleep and reduced hyperactivity, while psychological symptoms may have fluctuated as the patient confronted the emotional consequences of weight restoration.
The report’s authors present leptin as a hypothesis-generating treatment target rather than a ready-made therapy. A single retrospective case cannot separate the effects of metreleptin from those of increased food intake, weight gain, structured hospital routines, psychotherapy, medical monitoring or the passage of time. There was no untreated comparison patient, no random assignment and no way to determine whether the observed changes would have occurred without the hormone. Nor can the result establish the appropriate dose, duration, safety profile or long-term effects of metreleptin in adolescents with anorexia nervosa. Leptin treatment is also not a substitute for nutritional rehabilitation, psychiatric care or medical management of the potentially life-threatening complications of severe malnutrition. Nevertheless, the case may encourage controlled studies examining whether restoring a starvation-suppressed hormonal signal can reduce hyperactivity and improve sleep alongside conventional treatment. Carefully designed trials will be needed to determine whether this striking individual response represents a reproducible biological effect or an unusual coincidence within a complex recovery process.
