Prolactin is a hormone produced by the pituitary gland that is responsible for breast development and lactation, which acts both as a hormone and as a cytokine. Cytokines “can activate signalling pathways that promote cell growth and survival with increasing evidence of a role in cancers, such as breast and prostate.”
Symptoms of high prolactin levels include the following:
Amennorrhea (absence of menses).
Gynaecomastia (swelling of male breasts).
Women with naturally higher prolactin levels have higher risk of breast cancer according to a large epidemiologic study. High prolactin levels correlated in another study most positively with a risk of post-menopausal estrogen receptor positive or progesterone receptor positive breast cancers. Tamoxifen, a breast cancer drug, blocks the prolactin receptor from binding with prolactin, which may explain how tamoxifen works to treat breast cancer. Estradiol and weak environmental estrogens increase human prolactin production.
Hyperprolactinemia (high blood prolactin levels) is a serious risk factor for patients with breast cancer. Dopamine agonists are drugs that increase dopamine, such as Amantadine (Symmetrol) and bromocryptine. These drugs reduce prolactin levels, but they do not benefit breast cancer patients according to some studies.
One study showed that higher prolactin levels were a risk factor for metastases in women who already had breast cancer. The women with higher levels of prolactin had faster metastases of their breast cancers.
At the cellular level prolactin stimulates breast cancer growth, stimulates cytokine systems, and protects breast cancer cells from apoptosis (a natural form of cell death for abnormal cells.) Prolactin is being seen as a target for breast cancer treatment. New drugs are being developed to block prolactin both from the pituitary and of local origin, such as from breast cancer cells.
The elevation of prolactin levels by dopamine antagonists (anti-psychotic medications) was studied in large numbers of women. A six year study compared a group of women who took dopamine antagonists with a group of women who did not. The dopamine antagonists takers had a 16% increase in the rate of breast cancer. The increase risk of breast cancer was dose-related with the highest doses causing the highest rates of cancer.
Several research studies have shown that elevated prolactin in humans is a risk factor for both breast and prostate cancers. Since dopamine antagonists increase prolactin levels, there needs to be more study as to their effect. A number of pharmaceutical drugs cause hyperprolactinemia. Untreated Parkinson’s disease patients have elevated prolactin levels.
There is evidence for a role of prolactin in prostate cancer. Prolactin modulates and stimulates testosterone production in both rodents and humans. Androgens (male hormones) are related to prostate cancer and early treatment of prostate cancer is to disrupt androgen production. Prolactin is thought to promote prostate cell growth by cytokines, independent of androgens. Prolactin suppresses prostate cell apoptosis, a natural form of cell death for abnormal cells.
Bromocriptine reduces hyperprolactinemia in women with breast cancer and men with prostate cancer. Dopamine agonists reduce hyperprolactinemia even though some studies show they don’t benefit breast cancer treatment. Prolactin produced locally is not controlled by centrally acting dopamine agonists. The relationship of prolactin with prostate cancer is not as clear as the relationship between breast cancer and prolactin.
CONCLUSION: Dopamine antagonists, such as anti-psychotic drugs, are associated with higher rates of breast cancer as well as increased rates of metastases and faster metastases. Dopamine antagonists increase the production of prolactin, which is mitogenic, suppresses apoptosis, and stimulates breast cancer growth. Hyperprolactinemia is a serious side effect of anti-psychotic medications for women and may be for men. There is evidence that hyperprolactinemia has a higher level of significance for humans.
Hyperprolactinemia is a serious risk factor for patients who have breast cancer. Human breast cancer cells produce prolactin. Dopamine agonists reduce pituitary prolactin but do not alter the prolactin produced by the breast cancer cells.
“Elevation of prolactin should be considered an adverse event in humans.” “Tumor promotion in undiagnosed breast cancer is likely to be the most common adverse reaction of hyperprolactinemic drugs.”
NOTE: See summary #45 about Boswellia serrata. Boswellia, by blocking the 5-lipoxygenase enzymes, reduces the production of leucotrienes. This reduces the production of prolactin, which is stimulated by leucotrienes. Whether this is actually clinically significant remains to be proven.
The following are pharmaceuticals that are dopamine antagonists and can be the cause of hyperprolactinemia: Chlorpromazine (Thorazine), Clozapine (Clozaril), Haloperidol (Haldol), Olanzepine (Zyprexa), Quetiapine (Seroquel), Risperidone (Resperidal), Thioridazine HCl (Thioridazine), Thiothixene (Navane), Trifluoperazine (Stelazine).
To read the author’s abstract of the article click on the link to the author’s title of the article above.