Hyperprolactinemic hypogonadism is a neuroendocrine syndrome associated with excessive secretion of the hormone prolactin by the anterior pituitary gland and accompanied by a number of endocrine and somatogenic disorders. Pathology is manifested by menstrual dysfunction, pathological galactorrhea, hirsutism, infertility (in women), decreased libido, erectile dysfunction, gynecomastia, infertility (in men). Diagnosis is based on multiple determination of prolactin levels in the blood; conducting medical tests, skull x-ray, MRI of the brain, examination of the fields of vision; examination of the thyroid gland and reproductive system. When choosing tactics for the treatment of hyperprolactinemic hypogonadism, the cause of hyperprolactinemia is taken into account: with prolactinoma, surgical treatment is performed; in other cases, drug therapy with dopamine receptor agonists is carried out.
Meaning
Hyperprolactinemic hypogonadism is one of the most common types of hypothalamic-pituitary dysfunction characterized by hyperproduction of the hormone prolactin. This pathology occurs in 0.5% of the female and 0.07% of the male population in the general population. Disease is detected in 70% of women with infertility and 15-20% of patients with secondary amenorrhea. The disease is most often diagnosed at the age of 20-40 years. Hyperprolactinemic hypogonadism is also known in the literature as hyperprolactinemia syndrome, in women – persistent galactorrhea-amenorrhea syndrome.
Meanwhile, hyperprolactinemia and hyperprolactinemic hypogonadism are not always synonymous. An increase in the level of prolactin in the blood serum (hyperprolactinemia) can be asymptomatic (biochemical), physiological (during pregnancy, lactation, newborn) and pathological, accompanied by the development of hyperprolactinemic hypogonadism. In medicine, hyperprolactinemic hypogonadism is the subject of research in various clinical disciplines: endocrinology, gynecology, andrology, sexology.
Causes
Hyperprolactinemic hypogonadism may have an independent, primary significance, be combined with another pathology of the hypothalamic-pituitary system or have the character of symptomatic manifestations. As a primary disease, hyperprolactinemic hypogonadism develops with pituitary adenomas (micro- and macroprolactinoma). The causes of idiopathic hyperprolactinemia, which occurs in the absence of pituitary adenoma and other visible causes, are unknown.
When the peripheral endocrine glands are affected, the so-called symptomatic hyperprolactinemic hypogonadism develops, which may be caused by taking medications, hypothyroidism, polycystic ovary syndrome, chronic prostatitis, liver cirrhosis, kidney failure, etc. Hyperprolactinemic hypogonadism can be combined with hormonal inactive adenomas, “empty” Turkish saddle syndrome and other hypothalamic-pituitary disorders (craniopharyngioma, acromegaly, Cushing’s disease, lymphocytic pituitary, chronic intracranial hypertension).
Pathogenesis
A key link in the development of hyperprolactinemic hypogonadism of any genesis is the reduction or absence of the blocking effect of dopamine on the production of prolactin by the pituitary gland. This causes hyperplasia of prolactin-secreting cells at first, and then the formation of a pituitary microprolactinoma. In the case of symptomatic hyperprolactinemic hypogonadism, pharmacopreparations (antidepressants, aminazine, oral contraceptives, etc.) and endogenous hormones (melatonin, serotonin, steroids, tyroliberin, vasoactive intestinal polypeptide, etc.) can act as stimulators of dopamine transmission blockade and hyperprolactinemia.
Hyperprolactinemic hypogonadism is characterized by the development of a complex of reproductive, sexual, metabolic and emotional-personal disorders.
Symptoms
Manifestations of hyperprolactinemic hypogonadism in women
In women, hyperprolactinemia inhibits the cyclic release of gonadoliberin, which, in turn, is accompanied by a violation of the release of luteinizing and follicle-stimulating hormones, hypolyutein ovarian dysfunction, hypoestrogenism and hyperandrogenism. The extragenital effect of prolactin contributes to the enhanced transformation of carbohydrates into fats, which contributes to the development of obesity.
With the development of hyperprolactinemic hypogonadism in girls in the pre-pubertal period, hypoplasia of the uterus, labia minora, and clitoris is noted. Menstrual dysfunction occurs in women of childbearing age, the severity of which varies from oligomenorrhea to amenorrhea. Anovulation is accompanied by neuroendocrine infertility, for which patients are examined for a long time and treated by a gynecologist. Hypoestrogenia entails a decrease in sexual activity, frigidity, anorgasmia, vaginal dryness, dyspareunia.
The presence of pathological galactorrhea in hyperprolactinemic hypogonadism is detected in 70% of women. At the same time, the amount of pathological discharge from the mammary glands can be different – from single drops when pressed – to abundant and spontaneous expiration of a milk-like secretion. Typical is macromastia caused by fatty involution of the breast, which does not correspond to age. Pathological galactorrhea in hyperprolactinemic hypogonadism should be differentiated from fibrocystic mastopathy and breast cancer. A quarter of the patients have moderate hirsutism, expressed in excessive growth of facial hair, in the periarticular area and along the white line of the abdomen.
Manifestations of hyperprolactinemic hypogonadism in men
In men, under the influence of sustained hyperprolactinemia, testosterone secretion is inhibited, its conversion to dihydrotestosterone is reduced in target tissues, followed by suppression of the activity of secretory cells of the testicles and violation of spermatogenesis. Therefore, when examining the spermogram in men with hyperprolactinemic hypogonadism, oligozoospermia, asthenozoospermia, necrospermia are detected.
Hyperprolactinemia, which developed in boys in childhood, is accompanied by a delay in sexual development, underdevelopment of the genitals and secondary male sexual characteristics. In adult men with hyperprolactinemic hypogonadism, regression of secondary sexual characteristics, decreased libido, impotence, gynecomastia, infertility, galactorrhea is noted.
Other manifestations of hyperprolactinemic hypogonadism
Hyperprolactinemic hypogonadism caused by macroadenoma is accompanied by the development of neurological symptoms, metabolic and psychoemotional disorders.
Thus, the growth of a macroadenoma often causes compression of the intersection of the optic nerves, which leads to a limitation of the visual fields or a decrease in visual acuity. When the adenoma spreads into the cavity of the third ventricle of the brain, intracranial pressure increases, hydrocephalus develops, edema of the optic nerve. In the case of compression by a prolactin-secreting tumor of the pedicle and the posterior pituitary lobe, diabetes insipidus develops; when an adenoma spreads to the anterior pituitary lobe, hypopituitarism occurs. The germination of the tumor of the bottom of the Turkish saddle can lead to the spread of adenoma into the sphenoid sinus and the expiration of cerebrospinal fluid from the nose (rhinorrhea). When the tumor passes to the cavernous sinus, paralysis of the oculomotor, block, and diverting cranial nerves is possible. With the tumor genesis of hyperprolactinemic hypogonadism, patients are often disturbed by headache.
In addition to the suppression of reproductive and sexual functions, hyperprolactinemic hypogonadism develops metabolic diseases – osteoporosis, obesity, insulin-resistant diabetes mellitus. Among the psychoemotional disorders in hyperprolactinemic hypogonadism, insomnia, a tendency to depression, increased fatigue, memory impairment, etc. may be noted.
Diagnostics
Diagnostic tasks in case of suspected hyperprolactinemic hypogonadism are: identification of hyperprolactinemia and determination of its nature (tumor, symptomatic, idiopathic, medicinal).
A study of the concentration of prolactin in the blood serum reveals its increase by tens or even hundreds of times. Hyperprolactinemia is confirmed in the presence of increased prolactin levels in at least three blood samples. With prolactin levels above 200 ng/ml, one should think of a pituitary macroadenoma; less than 200 ng/ml – of a microadenoma or idiopathic hyperprolactinemia. Moderate hyperprolactinemia is characteristic of hypothyroidism, taking medications, diseases of the pelvic organs. Pharmacodynamic tests with metoclopramide, tyroliberin do not cause a significant increase in prolactin levels.
For the purpose of functional examination of the thyroid gland, hormonal parameters (T4 sv, TSH) are determined, an ultrasound of the thyroid gland is performed. If kidney damage is suspected, clinical blood and urine tests, biochemical parameters (electrolytes) are examined. In order to assess bone density, densitometry is performed. To determine the causes of hyperprolactinemia (mainly the detection of pituitary adenomas), an X-ray of the skull, CT or MRI of the brain or hypothalamic-pituitary region is performed.
Examination of the reproductive sphere in hyperprolactinemic hypogonadism involves ultrasound of the pelvis, gynecological examination (in women); ultrasound of the scrotum and prostate gland, spermogram examination – in men. The level of sex hormones (testosterone, estradiol, gonadotropins – LH, FSH) is determined. In the presence of chiasmal syndrome, it is necessary to consult an ophthalmologist with visometry, examination of the fundus and visual fields (perimetry), which makes it possible to exclude optic atrophy, optic neuritis, chorioretinitis, and other pathology.
Treatment
The method of treatment of hyperprolactinemic hypogonadism depends on the cause that caused it. With drug-induced hyperprolactinemia, a dose reduction or withdrawal of the drugs that caused the violation is required. In the case of symptomatic hyperprolactinemia associated with hypothyroidism, treatment with thyroid hormone preparations is prescribed.
To suppress the secretion of prolactin, the appointment of dopamine agonists (bromocriptine, cabergoline, L-DOPA) is indicated. Normalization of prolactin levels helps restore the synthesis of gonadotropins, menstrual cycle, sexual activity and fertility. In some cases, simultaneous use of chorionic gonadotropin or androgens in men is advisable.
With pituitary tumors that have caused the development of hyperprolactinemic hypogonadism, remote radiation therapy, drug therapy with dopaminomimetics can be performed. With adenomas resistant to conservative therapy, especially in the chiasmal region, a transnasal transsphenoidal adenomectomy is indicated. After such operations, pangypopituitarism often develops, and therefore hormone replacement therapy (hCG, thyroidin, etc.) is required.
Forecast
In most cases of hyperprolactinemic hypogonadism, therapy with dopaminomimetics can normalize prolactin levels, eliminate symptoms and restore fertility. Long-term remissions (over 5 years) are observed in 5-10% of patients after discontinuation of treatment. In a third of cases, spontaneous remission in women develops after childbirth or the onset of menopause.