What is hyperprolactinemia? A brief review

A brief review of hyperprolactinemia

1. العنوان الفرعي What is hyperprolactinemia ?

2. Hyperprolactinemia Hyperprolactinemia is defined as an increased level of prolactin in the blood . There are several reasons for the increase in this hormone. Some of them are related to the inhibition of dopamine,a neurotransmitter that exerts a negative control on prolactin. Therefore, a decrease in dopamine results in an increase in the blood prolactin rate. Furthermore, an increase in prolactin also influences the secretion of the hormone GnRH , which is responsible for regulating the production of the pituitary hormones FSH and LH. As a consequence, high prolactin levels cause anovulation in women and infertility.

3. Hyperprolactinemia: prolactin hormone Prolactin (PRL) is a hormone secreted by the pituitary gland, a gland at the base of the brain . Its main function is to stimulate the production of colostrum and breast milk in the mammary glands after childbirth. Prolactin is also involved in the synthesis of progesterone during the luteal phase of the menstrual cycle. Although the level of the hormone prolactin usually increases during pregnancy and lactation, it is normal for an adult woman to have values between O and 20 ng/ml.

4. Causes of hyperprolactinemia As we have already mentioned, pregnancy is the main cause of hyperprolactinemia in women. During gestation, the prolactin level may increase to 300 ng/ml. The same is true during breastfeeding, in which the baby stimulates the nipple when sucking milk causing continuous blockage in dopamine secretion. As a consequence, the decrease in dopamine causes more prolactin to be secreted, as both hormones are regulated by a negative feedback system. However, these are normal physiological situations in a woman's life in which the increase in blood prolactin is transient, just as it occurs during deep sleep, physical exercise, or orgasm. Once lactation is over, prolactin will return to normal levels and themenstrual cycle will re-establish itself.

5. Also, hyperprolactinemia can have some pathological causes, such as the following: Hypothyroidism • Pituitary adenomas ( prolactinomas ) • Chronic renal failure • Polycystic ovary syndrome (PCOS) • Hyperandrogenism Anorexia nervosa Other causes of hyperprolactinemia

6. Other causes of hyperprolactinemia There is also a type of iatrogenic hyperprolactinemia, caused by external factors such as neuroleptic drugs, antidepressants, anxiolytics, tranquilizers, opioids (morphine derivatives), and so on. All these drugs decrease the action and synthesis of dopamine. Finally, oral contraceptive pills with estrogens may also produce a moderate increase in circulatingprolactin in the blood.

7. 3. Signs and symptoms Everyone is different and not everyone will have the same symptoms when they have high levels of prolactin in their blood. The following are the most important signs and symptoms of hyperprolactinemia • Galactorrhea : secretion of milk by the mammary glands. It occurs in 30% of cases. • Primary or secondary amenorrhea: disappearance of menstruation. • Headaches and visual field alterations. These symptoms are caused by tumors. • Hirsutism, if the woman has PCOS and/or hyperandrogenism . • Osteoporosis, especially in cases of hypogonadism. • Decreased libido and dry vagina. • Infertility, mainly due to chronic anovulation. :

8. 4. Diagnosis The first diagnostic test that should be done in any patient with suspected hyperprolactinemia is to meaure bloodprolactin levels. To do this, a blood test must be done between the third and fifth day of the menstrual cycle, when the ovaries are at rest and hormones at basal levels. As indicated above, blood prolactin levels greater than 30 ng/ml indicate hyperprolactinemia disorder. If a prolactin result between 20 and 40 ng/ml is obtained, the analysis will be repeated to confirm the diagnosis.

9. A blood prolactin value greater than 200ng/ml in a non-pregnant woman may indicate a pituitary tumor. Treatment of high prolactin levels As noted above, prolactin levels can often be corrected by stopping or switching to a different medication. Correction of hypothyroidism is very effective also. If prolactin levels are persistently high, they can be effectively treated with a group of medications known as dopamine agonists .

10. Bromocriptine ( Parlodel ) . Parlodel is an effective and inexpensivemedication for high prolactin levels. Parlodel is usually taken at bedtime with a snack. This is because Parlodel will occasionally cause dizziness or stomach upset. so taking it before sleep and with food will reduce those side effects. generally with time, the side effects stop anyway. The prolactin levels can be rechecked in about three weeks. If the levels are still elevated the dose can be increased or a different medication can be tried. The Parlodel can be stopped upon diagnosis of pregnancy. However, if a woman has a macroadenoma , Parlodel should be continue through pregnancy and delivery.

11. Cabergoline ( Dostinex ) Because it is more expensive, cabergoline is not usually the first choice for treatment of high prolactin levels. It is usually used when Parlodel is ineffective or a woman cannot tolerate the side effects. Cabergoline is a longer acting medication. It is usually given twice a week instead of every day.

12. In a recent study by Uhr et al. (24), there was a clear the difference in the genotype distribution of rs2032583 and rs2235015 between remitters and non-remitters to antidepressant therapy in favor of C- and T-carriers respectively. Another study by Kato et al. (26) showed that the C-variant of rs1045642 and the G-variant of rs2032582 were similarly linked to a higher expression and function of P- gp , resulting in a poorer treatment response and lower remission rates to antidepressants. We, therefore, hypothesized that the C- and T-carriers of SNPs rs2032583 and rs2235015, linked to decreased function and activity of P- gp , could be a risk-the aggravating factor for the occurrence of side effects under cabergoline . On the contrary, the C-variant of rs1045642 and the G-variant of rs2032582 were found to lead to increased functionality of P- gp and therefore could be a protective factor against the occurrence of side effects. We, therefore, selected these four SNPs for genotyping analyses in our study .

13. In addition, it is important to review the medical history of the patient to determine the cause of this hormonal disturbance. Firstly, pregnancy has to be ruled out, and it must be taken into account whether the patient takes oral contraceptives, anxiolytic drugs, antidepressants, etc. Finally, it is also important to rule out the presence of any pituitary tumor using computed tomography (CT) or magnetic resonance imaging (MRI), especially if hyperprolactinemia is not associated with hypothyroidism.

14. ABCB1 is a gene that codes for a protein called P-glycoprotein, which plays an important role in transporting various substances across cell membranes. Cabergoline is a medication commonly used to treat hyperprolactinemia, a condition where there is an excessive production of the hormone prolactin, which can lead to a range of symptoms including irregular periods, infertility, and breast milk production. Studies have suggested that variations in the ABCB1 gene may affect the response to cabergoline treatment. Specifically, a particular ABCB1 gene polymorphism called C3435T has been shown to be associated with altered P-glycoprotein activity, which may influence the transport of cabergoline into cells and thereby affect its therapeutic efficacy. ABCB1