Prolactin Related Infertility

Hyperprolactinemia

Prolactin - The Hormone
Prolactin is a protein (197-199 amino acids) product of the anterior pituitary . Chemically similar to growth hormone and human placental lactogen .
A single gene located on chromosome 5 encodes it for prolactin synthesis and function .
Three types of prolactin have been identified based on differences in size and structural modifications that are the result of glycosylation , phosphorylation , additions and deletions-little , big and big big prolactin . Little prolactin has more biological activity than the bigger forms .

Sites of Secretion
Prolactin is secreted by the acidophils of the anterior pituitary . A glycosylated form of the hormone is secreted by the endometrium in the luteal phase and by the decidua of pregnancy .
Ectopic secretion though rarely seen , has been found to be associated with pituitary tissue in the pharynx , bronchogenic carcinoma , renal cell carcinoma , gonadoblastomas and ovarian dermoid tumors .

Control of Secretion
This is the only pituitary hormone whose control is mainly inhibitory ; the main factor involved is Dopamine – released by the hypothalamus into the portal system . Prolactin secretion is inhibited and stimulated by the association and dissociation of dopamine from its receptors (D2) on the acidophils .
Estrogens increases prolactin synthesis , while Serotonin and Thyrotropin Releasing Hormone (TRH) stimulate prolactin release . Other factors involved include angiotensin II , vasopressin , growth factors , vasoactive intestinal peptide (VIP),etc.

Functions
The primary function of Prolactin is to enhance breast development in pregnancy , and to induce lactation after delivery . In addition , by binding to specific receptors in the gonads , lymphoid cells and liver – it affects fertility , immunity and liver functions .

Etiology of hyperprolactinemia
Physiological Pathological
-REM sleep ; -tumors-prolactinoma;
-pregnancy ; -hypothalamic / pituitary lesions;
-nipple stimulation ; -idiopathic;
-stress ; -polycystic ovarian disease;
-coitus ; -hypothyroidism;
; -chest wall injury;
; -renal failure;
; -liver failure;
; -drugs-dopamine analogs
*Phenothiazines;
*Estrogens;
*Opiates;
*Cimetidine;
*Methyldopa;
*Reserpine .

Effect on Female Reproductive Function:
-disrupts normal follicular development;
-atresia of the dominant follicle;
-inhibits aromatase enzyme;
-inhibits progesterone synthesis by the corpus luteum;
-premature destruction of the corpus luteum;
-induces uterine adenomyosis ;

Effect on Male Reproductive Function:
--inhibits pulsatile LH release by the anterior pituitary;
-reduces testosterone synthesis;
-inhibits 5-alpha reductase activity;
-structural changes in the testes-Germ cell exfoliation
*disorganization of seminipherous tubules;
*increased tubule wall thickness;
*lipid accumulation in Leydig cells.

Common presenting symptoms in prolactin related disorders:
-amenorrhea;
-oligomenorrhea;
-galactorrhea;
-unexplained infertility;
-headache;
-visual field defects;
-symptoms of hypothyroidism;
-drug intake;
-decreased libido.

Adjuvant investigations in a case of hyperprolactinemia:
-Serum TSH;
-Blood urea nitrogen;
-Serum creatinine;
-Liver function tests;
-Visual fiels testing;
-CT;
-MRI.

Drugs used in the treatment of hyperprolactinemia:
-Bromocriptine oral or im.;
-Pergolide;
-Cabergoline.

If the only cause of infertility is chronic anovulation due to hyperprolactinemia , a 60-80% pregnancy rate can be achieved with medical therapy alone .