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.