Sleep in menopause: differential effects of two forms of hormone replacement therapy.

OBJECTIVES: The aim of the present study was to evaluate differences between two regimens of estrogen/progestogen replacement therapy on nocturnal sleep in postmenopausal women. METHODS: Twenty-one (21) postmenopausal women were studied. They were randomized into two treatment groups: (1) estrogen (Premarin 0.625 mg) and medroxyprogesterone acetate (Provera 5 mg) (n = 11) or (2) estrogen (Premarin 0.625 mg) and oral micronized progesterone (Prometrium 200 mg) (n = 10). Postmenopausal women were recorded for two consecutive nights in the sleep laboratory at baseline and again after 6 months of treatment in a randomized trial. The women also had to fill out evening and morning sleep and vigilance questionnaires for 7 days before baseline recordings and for 23 days before month 6 recordings. RESULTS: Sleep efficiency was found to be significantly improved in the micronized progesterone group. It increased by 8% (p = 0.014) with no such increase observed in the medroxyprogesterone acetate group. Time spent awake after sleep onset was also significantly improved in the micronized progesterone group but not in the medroxyprogesterone acetate group. On the other hand, menopausal symptoms and subjective measures of sleep (questionnaires) improved in both groups after treatment. CONCLUSION: This study suggests that medroxyprogesterone acetate and micronized progesterone are both effective for treating menopausal symptoms but that the latter might better improve the quality of sleep in postmenopausal women taking estrogen.

Pramipexole in the treatment of restless legs syndrome: a follow-up study.

The restless legs syndrome (RLS) is a condition characterized by unpleasant limb sensations occurring at rest and associated with an irresistible urge to move. Several treatments are used to treat RLS including benzodiazepines, opioids, dopaminergic agents, clonidine and anticonvulsant drugs such as carbamazepine and gabapentine. Dopaminergic agents are now considered the treatment of choice for RLS. Levodopa is effective in treating RLS; however, several patients treated with levodopa at bedtime developed morning or late afternoon restlessness. Recently, more attention has been paid to dopamine receptor agonists. Ergoline derivatives, bromocriptine and pergolide were found effective, but require concomitant administration of domperidone, a peripheral dopamine antagonist. In a recent study, we studied the efficacy and innocuity of pramipexole, a new dopamine agonist with a higher affinity for the D3 receptor subtype of the D2 family, in a double-blind, placebo-controlled, randomized trial. Pramipexole had major effects on RLS symptoms without severe side-effects. The present study aimed to assess the long-term efficacy of pramipexole. Seven patients were treated with the drug for a mean follow-up duration of 7.8 months. Treatment was started at a dosage of 0.25 mg, and progressively increased until the optimal therapeutic effect was obtained. Home questionnaires were completed for 7 consecutive days, after one month and after a mean of 7.8 months of treatment with pramipexole, assessing leg restlessness during the daytime, in the evening, at bedtime and during the night. There was no evidence of a decrease in the therapeutic effect of pramipexole in these patients, even 7.8 months after the initiation of treatment. The optimal dosage was 0.25 mg for one patient, 0.5 mg for five patients and 0.75 mg for one patient. While there was a progressive increase in severity of leg restlessness from daytime to nighttime before treatment, a suppression of leg restlessness was observed throughout the 24 h with a single dose of pramipexole at bedtime. The remarkable efficacy of pramipexole raises the possibility that the D3 receptors of the mesolimbic system may be more specifically involved in the physiopathology of RLS.

Restless legs syndrome improved by pramipexole: a double-blind randomized trial.

BACKGROUND: Restless legs syndrome (RLS) is characterized by leg paresthesia associated with an irresistible urge to move. Currently used dopaminergic agents, such as levodopa, pergolide, and bromocriptine, offer incomplete control of sensory and motor symptoms and induce severe side effects. OBJECTIVE: To assess the safety and efficacy of pramipexole, a full D3-receptor agonist, in the treatment of RLS. METHODS: Ten RLS patients were studied before and after two 1-month treatments (placebo and pramipexole) administered in a double-blind crossover fashion. The severity of sensory and motor manifestations was assessed by 1 week of home questionnaires and 2 consecutive nights of sleep laboratory recordings. The indexes of periodic leg movement during sleep (PLMS) and during wakefulness (PLMW) were used as primary outcome variables. RESULTS: Pramipexole dramatically reduced the PLMS index to normal values (Wilcoxon, p = 0.005). The PLMW index was also significantly reduced (Wilcoxon, p = 0.007). Pramipexole also alleviated leg discomfort at bedtime and during the night as measured by the home questionnaires. CONCLUSIONS: Pramipexole is the most potent therapeutic agent ever tested for RLS. Measures of both sensory and motor functions returned to normal values after treatment. Moreover, these results further support the hypothesis that D3 receptors play a major role in the physiopathology of this condition.