Evaluation Plasma levels of immunoreactive prolactin are 5 to 27 ng/mL throughout the normal menstrual cycle. Samples should not be drawn soon after the patient awakes or after procedures. Prolactin is secreted in a pulsatile fashion with a pulse frequency ranging from about 14 pulses per 24 hours in the late follicular phase to about 9 pulses per 24 hours in the late luteal phase. There also is a diurnal variation, with the lowest levels occurring in midmorning. Levels rise 1 hour after the onset of sleep and continue to rise until peak values are reached between 5 and 7 a.m. (256,257). The pulse amplitude of prolactin appears to increase from early to late follicular and luteal phases (258–260). Because of the variability of secretion and inherent limitations of radioimmunoassay, an elevated level should always be rechecked. This sample preferably is drawn midmorning and not after stress, previous venipuncture, breast stimulation, or physical examination, all of which transiently increase prolactin levels.
When prolactin levels are found to be elevated, hypothyroidism and medications should first be ruled out as a cause. Prolactin and TSH determinations are basic evaluations in infertile women. Infertile men with hypogonadism should be tested. Likewise, prolactin levels should be measured in the evaluation of amenorrhea, galactorrhea, hirsutism with amenorrhea, anovulatory bleeding, and delayed puberty (Fig. 31.9).
Physical Signs Elevations in prolactin may cause amenorrhea, galactorrhea, both, or neither. Amenorrhea without galactorrhea is associated with hyperprolactinemia in approximately 15% of women (261–263). The cessation of normal ovulatory processes resulting from elevated prolactin levels is primarily caused by the suppressive effects of prolactin, via hypothalamic mediation, on GnRH pulsatile release (243,261,262,264–272). In addition to causing a hypogonadotropic state, prolactin elevations may secondarily impair the mechanisms of ovulation by causing a reduction in granulosa cell number and FSH binding, inhibition of granulosa cell 17βestradiol production by interfering with FSH action, and by causing inadequate luteinization and reduced luteal secretion of progesterone (273–278). Other etiologies for amenorrhea are detailed in Chapter 30.
Although isolated galactorrhea is considered indicative of hyperprolactinemia, prolactin levels are within the normal range in nearly 50% of such patients (279–281) (Fig. 31.9). In these cases, whether caused by a prior transient episode of hyperprolactinemia or other unknown factors, the sensitivity of the breast to the lactotrophic stimulus engendered by normal prolactin levels is sufficient to result in galactorrhea. This situation is very similar to that observed in nursing mothers in whom milk secretion, once established, continues and even increases despite progressive normalization of prolactin levels. Repeat testing is occasionally helpful in detecting hyperprolactinemia. Approximately one-third of women with galactorrhea have normal menses. Conversely, hyperprolactinemia commonly occurs in the absence of galactorrhea (66%), which may result from inadequate estrogenic or progestational priming of the breast.
In patients with both galactorrhea and amenorrhea (including the syndromes described and named by Forbes, Henneman, Griswold, and Albright in 1951, Argonz and del Castilla in 1953, and Chiari and Frommel in 1985), approximately two-thirds will have hyperprolactinemia;
Hyperprolactinemia Review history, drug use, and physiologic etiologies