Gonadal sex hormones and dystonia: Experimental studies in genetically dystonic hamsters

Abstract

In some kinds of idiopathic dystonia, including paroxysmal dystonia, a role of sex hormones has been suggested because of female predominance and onset, recurrence, or exacerbation of dystonic symptoms with pregnancy. Similar effects of pregnancy have recently been reported in a model of paroxysmal dystonia, the genetically dystonic hamster. Dystonia in mutant hamsters of both genders is transient, i.e., exhibits spontaneous remission at around puberty, strongly suggesting involvement of gonadal sex hormones. For exploration of the role of sex hormones in dystonia, we undertook a series of ontogenetic experiments in male and female dystonic hamsters. Mutant animals of both genders exhibited the same postnatal development of dystonia with maximum severity of dystonic attacks between weaning and approximately 40 days of age and spontaneous remission thereafter. As shown by plasma sex hormone determinations and, in females, vaginal cytology, spontaneous improvement of the movement disorder coincided with puberty in both genders. Male and female hamsters had about the same plasma levels of progesterone. Compared with nondystonic hamsters, onset of puberty was significantly retarded in both male and female dystonic hamsters. Furthermore, body weight gain was lower in dystonic animals, indicating retarded postnatal development. Gonadectomy at time of weaning did not alter the age-dependent development and remission of dystonia, suggesting that gonadal sex hormones are not critically involved in the disease in hamsters. We propose that transient paroxysmal dystonia in mutant hamsters is caused by postnatal retardation of brain development resulting in a temporary impairment of brain functions with spontaneous remission independent of gonadal sex hormones. In view of the fact that the brain can synthesize steroids such as progesterone independent of peripheral glands in both genders, such neurosteroids might be involved in the postnatal brain maturation that leads to remission of dystonia at around puberty in mutant hamsters.

Onset and progression of primary torsion dystonia in sporadic and familial cases

“…These observations are in keeping with previous reports form England [27,28] and suggest that these clinical features are shared by other patients particularly amongst European population. These gender‐related variations support the possibility that sex hormones play a role in the pathophysiology of dystonia [29,30].…”

Oromandibular dystonia and hormonal factors: twelve years follow‐up of a case report

“…A relation between female hormones and movement disorders has been hypothesized (28, 29). Pregnancy has been reported to exacerbate movement disorders such as torticollis, hemimasticatory spasms, dystonia, chorea and restless leg syndrome (30–33). Oral contraceptive therapy has been indicated as a causative role in chorea (34) and paraballismus (35).…”

Menopause and Menarche in Patients with Primary Blepharospasm: An Exploratory Case-Control Study

“…A recent study observed a significantly retarded onset of puberty in genetically dystonic female hamsters in which dystonia spontaneously remits at around puberty [8]. In this setting, both dystonia and later menarche were interpreted as the result of postnatal retardation of the maturation of brain systems controlling the motor system and the hypothalamic-pituitary-gonadal axis, responsible for the onset of puberty.…”

“…As the peak age of BSP onset is in the 5th–6th decade [1], this raises the possibility that the drop in peripheral estrogen levels due to menopause contribute to the age-dependent development of the condition. A recent study observed a significantly retarded onset of puberty in genetically dystonic female hamsters as compared with nondystonic animals [8]. …”