Prolactin is a protein hormone (closely related to human growth hormone) that is secreted by specialized cells in the anterior part of the pituitary gland. In addition, the hormone is also produced and secreted by a broad range of other cells in the body, most prominently various immune cells, the brain, and the lining of the uterus. Most cells respond to prolactin. In fact it is hard to identify any tissue that does not have prolactin receptors.

Although prolactin’s major target organ is the breast, where it stimulates development and milk production, the hormone has many other functions. Several hundred different actions have been reported for prolactin.

Immune cells are rich in prolactin receptors and certain types of lymphocytes in fact synthesize and secrete prolactin. These observations suggest that prolactin may to some extent act as a regulator of the body’s immune activity.

In an area in the brain known as the hypothalamus, a chemical called dopamine is released. Dopamine suppresses prolactin synthesis and release by the pituitary gland. As such it acts as a “hypothalamic brake set” causing prolactin only to be secreted when the “brake” is released.

Several other hypothalamic hormones, including thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) cause an increase in prolactin secretion. Stimulation of the nipples (including but not limited to nursing) leads to hypothalamic activation and prolactin release Estrogens also exerts a positive control over prolactin synthesis and secretion.

Common manifestations of increased prolactin secretion (hyperprolactinemia) in women include amenorrhea (lack of menstrual cycles) and galactorrhea (excessive spontaneous breast secretion). Men with hyperprolactinemia may present with hypogonadism, decreased sex drive, sperm dysfunction resulting in infertility, and with impotence. Such men also can show breast enlargement (gynecomastia), but very rarely have galactorrhea.

Causes: Significantly raised blood prolactin levels (>60ng/ml) might point to a prolactin producing pituitary tumor (adenoma) which may be large (macroadenoma), small, or even microscopic (microadenoma). Markedly elevated blood prolactin is also associated with other types of intracranial lesions such as craniopharyngiomas, meningiomas etc. Prolonged treatment with bromocryptine (Parlodel) or related products will usually effectively lower blood prolactin concentration and lead to shrinkage of pituitary adenomas. Such treatment is also safe during pregnancy. Other intracranial lesions causing hyperprolactinemia are usually treated by surgical removal.

Certain drugs (e.g. tranquilizers, ganglion blocker antihypertensives, antidepressants, thiazides and narcotics) can also lead to a significant elevation in blood prolactin. Drug-induced hyperprolactinemia can be reversed by modifying or withdrawing the causative medication. In cases where this cannot safely be done, bromocryptine derivatives can be used.

Elevated Prolactin and female Reproductive Performance: It is important to recognize that even modestly raised prolactin levels (20ng/ml-40ng/ml) can interfere with response of the uterine lining to estrogen (i.e. endometrial proliferation) as well as ovarian follicle growth and development, thereby reducing reproductive potential, and may require treatment with prolactin suppressants such as Parlodel.

Hyperprolactinemia is often an early indicator of impending or existing thyroid hormone deficiency or hypothyroidism (Hashimoto’s disease) which in most cases results from antithyroglobulin and/or antimicrosomal antibodies that attack thyroid hormone producing glands, replacing them with connective tissue. In about 50% of cases where the woman has such thyroid antibodies in her blood (regardless of whether or not they have concomitant hormonal or clinical evidence of thyroid deficiency) she will also have increased natural killer cells activity(NKa). When this happens embryo implantation will likelyb be impaired and the woman will often present with inability to conceive (“infertility”), unexplained IVF failure, or with recurrent pregnancy loss (RPL).

It is my opinion that all women who manifest with such reproductive problems, women who have a personal or family history of hypothyroidism and those in whom hyperprolactinemia or elevated blood levels of thyroid stimulating hormone (TSH) are detected, be tested for antithyroid antibodies and NKa (using the K-562 target cell assay) and that women found to have such antibodies as well as NKa, undergo selective immunotherapy with Intralipid (IL) infusions plus steroid (prednisone, prednisilone, dexamethasone) therapy to down-regulate NKa. IL is administered intravenously 7-14 days prior to embryo transfer (or about 4-7 days prior to ovulation or egg retrieval) and then repeated once more, immediately upon biochemical confirmation (beta hCG blood test) of embryo implantation. The steroids are continued to the 10th week of pregnancy and then slowly tailed off.

What often goes unrecognized is that treatment of hypothyroidism with thyroid hormone replacement alone, while resolving the hormonal imbalance associated with hypothyroidism will usually not resolve associated reproductive dysfunction due to associated immunolgic imlantation dysfunction .