To determine the mechanisms by which calcium channel blockade with verapamil causes hyperprolactinemia, the authors investigated the effects of this blockade on the prolactin (PRL) responses to stimulation by thyrotropin releasing hormone (TRH) and inhibition by dopamine, using L-dopa and bromocriptine. Verapamil, given for 1 week at a dosage of 240 mg orally to eight healthy volunteers, induced a significant elevation of basal PRL levels (17.3 ± 1.8 ng/ml to 30.9 ± 4.3 ng/ml, p < 0.005). Verapamil also caused an increase in the PRL response to a TRH (100 μg). However, when the increased basal level was considered by calculating the area under the TRH response curve and subtracting the basal values, this increase (1763.4 ± 202.6 ng/ml · min to 2260.6 ± 223.9 ng/ml · min) was not found to be statistically significant (p > 0.05). Verapamil had no effect on the basal or TRH- stimulated thyroid stimulating hormone levels. In these same volunteers, PRL levels decreased from 13.2 ± 2.5 ng/ml to a nadir of 5.5 ± 1.6 ng/ml in response to L-dopa. After 1 week of verapamil 240 mg, basal PRL levels were elevated to 21.5 ± 3.1 ng/ml, then decreased to 8.2 ± 1.8 ng/ml with L- dopa. The percentage decreases in PRL in response to L-dopa (60 ± 5% versus 62 ± 3%) were not significantly different (p > 0.05). Verapamil had no effect on the basal or L-dopa-stimulated growth hormone levels. Bromocriptine 2.5 mg given to five volunteers twice daily caused PRL levels to fall from 13.3 ± 1.6 ng/ml to 5.0 ± 0.9 ng/ml. The addition of verapamil 240 mg daily did not significantly alter this suppression of PRL levels. Calcium channel blockade with verapamil resulted in sustained elevation of PRL levels without affecting the PRL response to TRH or impairing the inhibition of PRL by L- dopa or bromocriptine. Because it is likely that this sustained PRL elevation was due to a decrease in dopamine action, this effect may have resulted from a decrease in dopamine release by TIDA neurons. Alternatively, this effect could have been the result of an decrease in dopamine action on the lactotroph. However, the verapamil was not able to block the large pharmacologic amounts of dopamine generated from the L-dopa or block the large dopamine effect from the dose of bromocriptine used in this study.
- Amenorrhea, Bromocriptine
- Calcium channel
- Galactorrhea, Hyperprolactinemia, Prolactin
ASJC Scopus subject areas