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 .