**5. Physiological causes**

#### 1. Pregnancy

220 Prolactin

**Drugs**  Estrogens

cisapride.

Verapamil Fluoxetine

Serotonin Noradrenaline

HRT

**Other**

Liver cirrhosis

Convulsions

Iv: intra-venous

antidepressants.

Protease inhibitors

Beta endorphins GABA

**Neurogenic causes** Thoracic wall lesions Spinal cord lesions Breast stimulation

Primary hypothyroidism Chronic renal insufficiency

Suprarenal insufficiency Polycystic ovary syndrome

GABA: Gamma-aminobutyric acid HRT: Homone replacement therapy

Idiopathic macroprolactinemia

**Table 1.** Hyperprolactinemia causes

Benzodiazepine Cimetidine (iv)

Empty-sella syndrome Cushing disease

Lymphocytic hypophysitis

Antihypertensives: reserpine, methyldopa.

Adrenergic receptor antagonists (medroxalol)

Opiates: cocaine, morphine, heroine.

Antipsychotics: phenothiazine (chlorpromazine, perphenazine, fluphenazine, thorazine,

The most important cause of hyperprolactinemia is the secretory pituitary adenoma. Nevertheless, the most common cause are drugs and, when it is possible, the serum

prolactin determination should be done once those are suspended.

Other dopaminergic blockers: metoclopramide, sulpiride, domperidone, cisperidone,

Antidepressant: monoamine oxidase inhibitors (imipramine), amoxapine, Tryciclic

promazine, fluoperazine, trifluoperazine, etc.), haloperidol, butyrophenone.

Serum prolactin rises in a progressive way during gestation, but in a variable manner (18- 19). At the end, the mean value is around 200 ng/ml but the range is 35-600.

Around the 6th week from the labor the normoprolactinemia is restored. Although the prolactin concentration is high before the labor, the milk secretion only takes place after it, because the high presence of estrogens and progesterone in pregnant women has an inhibitory effect over the milk secretion. When these hormones levels drop after the labor, lactation is produced.

During gestation the prolactin levels in the amniotic liquid can reach the 1000 ng/ml, higher concentration that any other organic fluid, this happens around the 15th and the 20th week of gestation and it drops slowly until the end of the pregnancy to 450 ng/ml. It is supposed to be produced by the fetal and the mother´s hypophysis, with a possible function of fetal osmoregulation to survive in the intrauterine liquid environment, helping and contributing to the pulmonary maturing raising the content of phospholipids and changes in the lecithinsphingomyelin ratio (20).

2. Breast stimulation

Nipple suction, probably by neural via, during breastfeeding, rises the serum values of prolactin, especially in the first weeks after giving birth in direct relation to the lactotroph hypertrophy by the estrogenic stimulus of the pregnancy (18-20)

3. Stress

Any kind of stress, physical or psychical, can cause hyperprolactinemia, which is normally slight, and rarely over 40 ng/ml.

4. Sexual contact

There is a dopamine decreasing after orgasm, immediately, the prolactin rises, in men and women, acting as a sexual satiation mechanism (21). In men, without any doubt contributes to the "turn around and snore" phenomenon. In women, its effects can be delayed.

Kruger TH et al have demonstrated that sexual intercourse with orgasm induced not only the well-established immediate prolactin increasing of 300% but also an additional prolactin elevation around noon of the next day. These fluctuations were measured on top of regular circadian rhythm (22).
