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most frequently occurring adenoma. Prolactinomas affect womenmoreoften than men. For instance, the incidence is 3.38 times greater in womenthan in men in Japan. Most prolactinomas in womenare microadenomas (<1 cm in diameter) and occur at childbearing ages, while those in menare more frequently macroadenomas and occur evenly distributed throughout their adult life span. In general, the larger the tumor, the higher the PRL level in blood. The elevated PRL level in blood (hyperprolactinemia) causes gonadal dysfunction or infertility by inhibiting the GnRH-LH/FSH-gonadal axis probably through the effect on the hypothalamus. Typical symptoms are irregular menses, amenorrhea, and galactorrhea in womenand decreased libido and impotence in men. Another important issue related to hyperprolactinemia is decreased bone density or osteoporosis associated with hypogonadism. This bone complication should not be overlooked because if left untreated, it potentially increases a risk of fractures. Microadenomasrarely progress to macroadenomas; the risk of progression is only 7% (1). Tumor growth is usually directed upward into the suprasellar cistern (suprasellar extension). The tumors that are large enoughto compress optic chiasm and adjacent structures produce symptoms of mass effects, including headache, decreased vision, and narrowing of visual fields, typically bitemporal hemianopsia. Furthermore, direct compression of normal pituitary tissues and, occasionally, invasion into the hypothalamus causes single or multiple pituitary hormone deficiency, i.e. hypopituitarism of the pituitary and hypothalamic origin. For these reasons, prolactinomas should be sufficiently treated at the appropriate time. The goal of treatment is to reduce or eliminate hormonaloverproduction and local mass effects and to restore or preserve normal pituitary function. Secretion of PRL by the pituitary is under tonic inhibition by dopamine, a PRL-inhibiting factor delivered from the hypothalamus. Although prolactinoma pathogenesis remains to be proved, prolactinoma retains biochemical characteristics of normal PRLcells (lactotrophs) and responds to dopamine. Dopamine receptor agonists suppress PRL secretion in prolactinoma patients as in healthy subjects. Bromocriptine was the first dopamine agonist in worldwide clinical use for treatment of hyperprolactinemia and prolactinomas (1). It can normalize elevated PRL levels in 80-90% of prolactinoma patients (1) and thereby restore normal gonadal function, cease galactorrhea, and recover visual disturbance in a majority of patients. In addition, bromocriptine shrinks 70% of prolactinomas more than 25% (1) and makes some tumors disappear. The mechanism by which dopamineagonists reduce tumor size involves a suppression of PRLsynthesis and PRLgene transcription. The normalization rate of hyperprolactinemia by bromocriptine is greater than that achieved by neurosurgery, i.e. transsphenoidal tumor removal. The long-term surgical cure rate is 5060%, although initial normalization of PRLis attained in about 70%of patients. This is the reason whydopamine agonists have been used as a first-line treatment in prolactinomas during the last two decades. By contrast, surgery remains a treatment of choice for other functioning and non-functioning pituitary tumors. Currently available dopamine receptor agonists for hyperprolactinemia in Japan are bromocriptine and terguride. In general, these drugs are well tolerated and side effects are usually mild and transient. Commonside effects are such gastrointestinal symptomsas nausea, vomiting, and constipation, and dizziness or vertigo associated with orthostatic hypotension. To minimize these side effects, bromocriptine is initially started at a low dose (1.25 mg) with a snack at a bedtime and gradually increased to 2.5 mg twice or three times a day over a period of a few weeks. However, approximately 5% of patients experience side effects of sufficient severity, which limits the dose and even necessitates withdrawal of the medication. Drug intolerance is a considerable frustration for clinicians as well, if there is no alternative choice of treatment. In the August issue of this journal (2), Sabuncu et al from Turkey compared the efficacy and tolerability of a new dopaminergic agent, cabergoline, with those of bromocriptine in prolactinoma and non-tumoral (idiopathic) hyperprolactinemia.

Cabergoline, a Hopeful Medicine for Prolactinomas and Non-tumoral Hyperprolactinemia