The clinical presentation is consistent with hyperprolactinemia, which has caused bilateral galactorrhea and decreased libido. All of the listed medications have dopamine-blocking actions and can cause hyperprolactinemia with the exception of bromocriptine.
Prolactin is released from the anterior pituitary and normally functions to stimulate milk production in breast tissue and to inhibit ovulation through inhibition of GnRH. The release of prolactin is normally under tonic inhibition by dopamine released from hypothalamic neurons. Thus, dopamine agonists, such as bromocriptine, will inhibit prolactin secretion and form the basis of medical therapy for hyperprolactinemia; conversely, dopamine antagonists (such as many antipsychotic medications) can stimulate prolactin production by decreasing inhibition by dopamine. Hyperprolactinemia has many causes including pregnancy, prolactinoma in the anterior pituitary, hypothyroidism (due to the stimulating effects of increased TRH on prolactin production) and medication effects of dopamine antagonists. Symptoms include abnormal milk production in the breast with expression of the milk from the nipples (galactorrhea), menstrual abnormalities, reduced libido (due to the inhibitory effects of prolactin on the GnRH-FSH/LH endocrine axis), and a predisposition to osteoporosis.
Leung and Pacaud provide an overview of the diagnosis and management of galactorrhea. Diagnostic studies include tests for pregnancy, serum prolactin and TSH levels, and MRI scanning to rule out pituitary tumors. Pharmacologic management of hyperprolactinemia is done with dopamine agonists such as cabergoline and bromocriptine. When pituitary tumors are present, surgical resection may be indicated.
Peuskens et al. review the effects of second-generation antipsychotics on serum prolactin levels. They note that among the second-generation antipsychotics, amisulpride, risperidone, and paliperidone are the worst offenders in terms of causing increased prolactin secretion, while aripiprazole and quetiapine have a more favorable profile. However, any of the second-generation antipsychotics can cause this condition.
Illustration A exhibits the normal inhibition of prolactin release by dopamine produced in the hypothalamus.
Illustration B shows a MRI scan with a prolactinoma, which is a common cause of hyperprolactinemia. In the case of a prolactinoma, associated symptoms might include visual field abnormalities (due to mass effect on the optic chiasm) and headaches (due to increased intracranial pressure).
Answers 1, 2, 4, 5: All of these medications inhibit dopamine signaling and can therefore lead to hyperprolactinemia and its associated symptoms. Haloperidol and fluphenazine are first-generation antipsychotics that block the dopamine D2 receptor in the hypothalamic tuberoinfundibular system. Risperidone is a second-generation antipyschotic, while metoclopramide is an antiemetic agent; both can lead to hyperprolactinemia through dopamine D2 receptor blockade.
Leung AKC, Pacaud D. Diagnosis and management of galactorrhea. Am Fam Physician. 2004 Aug 1; 70(3):543-550.
PMID:15317441 (Link to Abstract)
Peuskens J, Pani L, Detraux J, De Hert M. The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. CNS Drugs. 2014 May;28(5):421-53.
PMID:24677189 (Link to Abstract)