Emiliano, 2004 From Galactorrhea to Osteopenia: Rethinking Serotonin - Prolactin Interactions

[Barbarannamated]

Recent discussion of menopause prompted me to search for studies discussing the role of SSRIs in gonadal/ovarian function with amenorrhea (cesation of menses) which can be misdiagnosed as menopause.FROM GALACTORRHEA to OSTEOPENIA: RETHINKING SEROTONIN - PROLACTIN INTERACTIONSFull text: http://www.nature.com/npp/journal/v29/n5/full/1300412a.htmlAna B F Emiliano and Julie L FudgeDepartment of Psychiatry, University of Rochester Medical Center, Rochester, NY, USNeuropsychopharmacology (2004) 29, 833–846, advance online publication, 3 March 2004; doi:10.1038/sj.npp.1300412ABSTRACTThe widespread use of the selective serotonin reuptake inhibitors (SSRIs) has been accompanied by numerous reports describing a potential association with hyperprolactinemia. Antipsychotics are commonly known to elevate serum prolactin (PRL) through blockade of dopamine receptors in the pituitary. However, there is little awareness of the mechanisms by which SSRIs stimulate PRL release. Hyperprolactinemia may result in overt symptoms such as galactorrhea, which may be accompanied by impaired fertility. Long-term clinical sequelae include decreased bone density and the possibility of an increased risk of breast cancer. Through literature review, we explore the possible pathways involved in serotonin-induced PRL release. While the classic mechanism of antipsychotic-induced hyperprolactinemia directly involves dopamine cells in the tuberoinfundibular pathway, SSRIs may act on this system indirectly through GABAergic neurons. Alternate pathways involve serotonin stimulation of vasoactive intestinal peptide (VIP) and oxytocin (OT) release. We conclude with a comprehensive review of clinical sequelae associated with hyperprolactinemia,The classic manifestations of hyperprolactinemia are galactorrhea, amenorrhea, infertility, and decreased libido in women, and erectile dysfunction, hypogonadism, and infertility in males (Gomez et al, 1977; Carter et al, 1978; Segal et al, 1979; Seppala, 1978). Long-term clinical consequences of hyperprolactinemia are less obvious, and include osteopenia in men and women (Greenspan et al, 1986; Jackson et al, 1986; Klibanski et al, 1988) and the possibility of an increased risk of breast cancer in women (Welsch and Nagasawa, 1977; Kwa et al, 1981). PRL levels associated with impaired fertility, decreased bone density and breast cancer have not been established. However, these conditions have a major public health impact and are therefore of special interest.ALTERED FERTILITYMenstrual disturbances associated with hyperprolactinemia range from luteal phase dysfunction with normal menses to frank amenorrhea (Bohnet et al, 1976; Katz and Adashi, 1990; Yazigi et al, 1997). Subtle abnormalities in PRL secretion may impact fertility. In a study of women with infertility of unknown etiology, the normal midcycle increase of PRL was absent in the patients, but maintained in healthy controls. All subjects had normal basal PRL levels, implicating loss of normal pulsatility in fertility problems (Subramanian et al, 1997). Consistent with this, altered fertility associated with only modestly elevated PRL levels is well recognized with antipsychotic drug use (Dickson and Glazer, 1999; Kinon et al, 2003; Smith, 2003), but has not been studied with respect to SSRIs. Aberrant PRL levels can interfere with female fertility through both CNS and peripheral mechanisms. At the hypothalamic level, high PRL interferes with LH pulsatility due to abnormalities in GnRH secretion (Sauder et al, 1984). Another mechanism is a direct inhibitory effect of PRL on ovarian follicular development and steroidogenesis (McNatty, 1979). Corpus luteum deficiency is also a mechanism of infertility due to PRL's luteolytic effect (Kredentser et al, 1981).Received 19 September 2003; Revised 30 December 2003; Accepted 13 January 2004; Published online 3 March 2004.

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Thanks, Barb. Please include lead author and year of publication in the topic title when posting in Journals.