Androgens in Health and Disease.pdf - E Library

Chapter 15/Androgens and Cognition 301
Fig. 6. Mean intraindividual difference scores in CAH and controls on the Primary Test of
Mental Abilities reflecting the relative strength of spatial vs perceptual speed abilities in the
four groups. Difference scores were calculated by subtracting the perceptual speed quotient
from the spatial quotient for each child. A positive value indicates relatively greater proficiency
in the spatial domain. Error bars represent the standard error of the mean. (From ref. 95,
reproduced with permission.)
effect of androgens in this population. Although other studies have failed to find an
advantage of spatial abilities in CAH girls (85,92), evidence of behavioral masculinization
has also been reported in CAH girls (96–103). Thus, additional carefully designed
studies may provide further information regarding the organizational effects of androgens
on cognition in this population.
Isolated Hypogonadotropic Hypogonadism and Kallmann’s Syndrome
Isolated hypogonadotropic hypogonadism (IHH) results from deficiency of gonadotropin-releasing
hormone (GnRH) from the hypothalamus. When this type of hypo-gonadism
is accompanied by anosmia from agenesis or malformation of the olfactory bulb, sulci, and
tracts, this condition is termed Kallmann’s syndrome (KS). It occurs in about 1 in 10,000
male births and males predominate in a ratio of 5 : 1. The syndrome can occur as an
inherited or sporadic disorder. X-Linked, autosomal-dominant, and autosomal-recessive
modes of inheritance have been described. For one-third or more of patients with KS, the
defect is likely the result of an X-linked form of KS, caused by a defect in KAL. KAL
encodes a protein, anosmin, that plays a key role in the migration of GnRH neurons and
olfactory nerves to the hypothalamus (104). MRI studies have confirmed the absence or
aplasia of the olfactory bulb in KS vs IHH patients (105). In IHH without anosmia, a defect
in the GnRH receptor (GnRHR) has been reported to be responsible for reproductive
function failure, and GnRHR mutations may be more common than previously appreciated
in familial cases of normosmic IHH (106). Individuals are typically identified during
adolescence when they evidence failure or a delay of puberty. It has been suggested that
developmental anomalies arise in the CNS as a result of a chronic lack of T and estradiol.
Reported neurologic abnormalities include anosmia, hyposmia, ocular motor abnormalities,
pes cavus foot deformities, and impaired smooth pursuit eye movements and mirror
movements (any synchronous movement of a corresponding muscle of another extremity