Persistent galactorrhea-amenorrhea syndrome: causes, symptoms, diagnosis, treatment

Persistent galactorrhea-amenorrhea syndrome (synonyms: Chiari-Frommel syndrome, Ahumada-Argones-del Castillo syndrome - named after the authors who first described this syndrome: in the first case in women who have given birth and in the second - in women who have not given birth). Galactorrhea in men is sometimes called O'Connell syndrome. The main clinical symptom is galactorrhea, which can be observed both against the background of hyperprolactinemia and normoprolactinemia. Normoprolactinemic galactorrhea usually occurs without concomitant amenorrhea. Hyperprolactinemic galactorrhea is combined with two other clinical manifestations of the disease - menstrual irregularities and infertility.

Causes of persistent galactorrhea-amenorrhea syndrome

One of the main causes of persistent galactorrhea-amenorrhea syndrome are pituitary adenomas - micro- and macroprolactinomas. Tumors of parasellar and hypothalamic localization can provoke persistent galactorrhea-amenorrhea syndrome. Traumatic genesis of the disease (rupture of the pituitary stalk) and inflammatory-infiltrative genesis (sarcoidosis, histiocytosis-X) are also possible.

Hyperprolactinemic hypogonadism can be observed in intracranial hypertension and in the syndrome of the "empty" sella turcica.

Knowledge of the listed etiologic causes determines the initial tactics of the doctor with mandatory neurological examination of the patient (X-ray of the skull, fundus, visual fields, computed tomography). In addition, a fairly common cause of persistent galactorrhea-amenorrhea syndrome is the long-term use of pharmacological agents that change the neurochemistry of the brain - inhibitors of monoamine synthesis (tx-methyldopa), agents that reduce monoamine reserves (reserpine), dopamine receptor antagonists (phenothiazines, butyrophenones, thioxanthenes), inhibitors of neuronal reuptake of mediator monoamines (tricyclic antidepressants), estrogens (oral contraceptives), drugs.

One of the common causes of persistent galactorrhea-amenorrhea syndrome is decompensation of constitutional biochemical hypothalamic defect with development of dopaminergic system insufficiency in the tuberoinfundibular region. In these cases, the terms "idiopathic hyperprolactinemia" and "functional hypothalamic hyperprolactinemia" are sometimes used.

A decrease in the inhibitory effects of the central nervous system on prolactin secretion as a result of unfavorable environmental influences (emotional stress - acute or chronic, exhausting prolonged physical exertion) can lead to hyperprolactinemia with the formation of the prolactin syndrome.

Pathogenesis of persistent galactorrhea-amenorrhea syndrome

The disease is based on hyperprolactinemia, which is the result of a disorder of the hypothalamic-pituitary dopaminergic mechanisms. Dopamine is a physiological inhibitor of prolactin secretion. Insufficiency of dopaminergic systems in the tuberoinfundibular region of the hypothalamus leads to hyperprolactinemia; it can also be caused by the presence of a prolactin-secreting pituitary tumor. In the formation of pituitary macro- and microadenomas, great importance is attached to hypothalamic disorders of catecholamine control of prolactin secretion, which can cause excessive proliferation of cyclolactaphores in the pituitary gland with possible further formation of a prolactinoma.

Symptoms of persistent galactorrhea-amenorrhea syndrome

Galactorrhea should be considered a varying degree of secretion of milk-like secretion from the mammary glands, which continues for more than 2 years after the last pregnancy or occurs independently of it. The degree of expression of galactorrhea can vary significantly - from single drops of secretion with strong pressure on the mammary glands in the nipple area to spontaneous secretion of milk. Menstrual cycle disorders manifest themselves in the form of secondary amenorrhea or oligomenorrhea, less often primary amenorrhea can be observed. Most often, galactorrhea and amenorrhea develop simultaneously. As a rule, patients are found to have atrophy of the uterus and appendages, monotonous rectal temperature. It should be borne in mind that in the first years of the disease, atrophic changes in the internal genital organs may be absent.

They reveal the absence of orgasm and difficulties during sexual intercourse as a result of a significant decrease in vaginal secretion. Both a decrease and an increase in body weight may be observed. Hirsutism is usually moderate. Pale skin, pastosity of the face, lower extremities, and a tendency to bradycardia are noted. The syndrome of persistent galactorrhea-amenorrhea may be combined with other neurometabolic-endocrine syndromes - cerebral obesity, diabetes insipidus, idiopathic edema.

In the emotional-personal sphere, unexpressed anxiety-depressive disorders prevail. As a rule, the disease begins at the age of 20 to 48 years. Spontaneous remissions are possible.

Differential diagnosis

It is necessary to exclude pathology of peripheral endocrine glands, which can lead to secondary hyperprolactinemia and symptoms characteristic of persistent galactorrhea-amenorrhea syndrome. This refers to diseases such as primary hypothyroidism, tumors producing estrogens, Stein-Leventhal syndrome (polycystic ovary syndrome), congenital dysfunction of the adrenal cortex. Chronic renal failure should also be excluded. It is known that in 60-70% of people with this disease, the level of prolactin increases. Its increase is also observed in cirrhosis of the liver, especially in hepatic encephalopathy. Tumors of non-endocrine tissues with ectopic production of prolactin (lungs, kidneys) should be excluded. In case of damage to the spinal cord and chest walls (burns, incisions, shingles), if the IV-VI intercostal nerves are involved in the process, galactorrhea may develop.

Treatment of persistent galactorrhea-amenorrhea syndrome

Therapeutic tactics depend on the causes of hyperprolactinemia. When a tumor is verified, surgical intervention or radiation therapy is used. In the absence of tumor or inflammatory-infiltrative lesions of the central nervous system, the use of anti-inflammatory, resorption, dehydrating therapy or radiotherapy is not indicated. The main drugs for the treatment of persistent galactorrhea-amenorrhea syndrome are ergot alkaloid derivatives: parlodel (bromocriptine), lisenil (lisuride), metergoline, as well as L-DOPA, clomiphene.

Parlodel is a semi-synthetic ergot alkaloid that is a specific dopamine receptor agonist. Due to its stimulating effect on hypothalamic dopamine receptors, parlodel has an inhibitory effect on prolactin secretion. It is usually prescribed in a dose of 2.5 to 10 mg/day, used daily for 3-6 months. Lisenil is prescribed in a dose of up to 16 mg/day. Other ergot alkaloids are also used: ergometrine, methysergide, metergoline, however, the therapeutic tactics of their use are under development.

The therapeutic effect of L-DOPA is based on the principle of increasing the content of dopamine in the central nervous system. L-DOPA is used in a daily dose of 1.5 to 2 g, the course of treatment is usually 2-3 months. There are indications of the drug's effectiveness in normoprolactinemic galactorrhea. It is believed that this drug can directly affect the secretory cells of the mammary gland and reduce lactorea. If there is no effect during the first 2-3 months of use, further therapy is inappropriate.

Clomiphene (clomid, clostilbegit) is prescribed at a dose of 50-150 mg/day from the 5th to the 14th day of the menstrual cycle induced by the previous administration of infecundin. 3-4 courses of treatment are carried out. The drug is less effective than parlodel.

To treat persistent galactorrhea-amenorrhea syndrome, a serotonin receptor blocker is used - peritol (citroheptadine, deseril). The effectiveness of the drug is controversial: it does not help all patients, and clear criteria for its use have not been developed. Treatment tactics using parlodel or lisenil are preferable.