Treatment of persistent galactorrhea-amenorrhea syndrome

Drug therapy occupies a major place in the treatment of all forms of persistent galactorrhea-amenorrhea syndrome of hypothalamic-pituitary genesis. In case of adenomas, it is supplemented or competes with neurosurgical intervention or radiation therapy. Until the 1970s, SPGA was considered incurable. However, this idea changed after the introduction of the semi-synthetic ergot alkaloid parlodel (bromocriptine) into medical practice, which has the properties of a hypothalamic and pituitary dopamine agonist (DA-mimetic), and is also capable of inhibiting the growth of prolactinomas in some patients by affecting the genetic apparatus of prolactotrophs.

The sequence of application of various treatment methods and their choice in each specific case are still controversial.

In the "idiopathic" form of persistent galactorrhea-amenorrhea syndrome, treatment with parlodel is indicated to restore fertility, normalize the menstrual cycle, and eliminate sexual, endocrine-metabolic, and emotional-personal disorders associated with hyperprolactinemia. If the concept of a single genesis of the disease with the transition of "idiopathic" forms to microadenoma is correct, the use of parlodel may have a preventive value.

Parlodel is used according to the scheme, starting with 1.25 mg (0.5 tablet) of the drug 1-3 times a day during meals with a further increase to 2.5 mg (1 tablet) 2-4 times a day. In refractory patients, significantly higher doses are acceptable. A single dose of parlodel inhibits prolactin secretion for an average of 12 hours. The drug reduces prolactin levels to normal, reduces lactorrhea, and restores a two-phase menstrual cycle. Ovulation occurs in the 4th-8th week of treatment. In cases where infertility is caused only by hyperprolactinemia, restoration of fertility is possible in 75-90% of cases. During treatment, most patients lose weight, and headaches are less common; some note a decrease in sexual disorders, an improvement in the emotional background, a decrease in acne, sialorrhea, and normalization of hair growth. The drug is relatively well tolerated, possible side effects include nausea, constipation, a feeling of nasal congestion, and dizziness. They decrease or stop during treatment, and sometimes it is necessary to temporarily reduce the dose of the drug. In patients with adenomas, parlodel primarily causes a violation of prolactin secretion and a decrease in the size of tumor cells, less often - dystrophic and degenerative changes in tumor cells, up to their necrosis, and ultimately - cell involution and a decrease in size, and sometimes - complete disappearance of the tumor. The effect of treatment depends on the degree of tumor differentiation - the more differentiated it is, the stronger. Refractory to the drug (i.e., no decrease in prolactin levels even with an increase in the dose of the drug to 25 mg / day, 10 tablets per day) is rare. In the event that treatment with parlodel, normalizing prolactin levels, is not accompanied by ovulation, a combination of this drug with gonadotropins or clomiphene is used.

Developmental abnormalities in children born to mothers who took parlodel are not more common than in the population on average. The drug does not have an abortive effect. Some researchers note the predominance of boys and relatively accelerated mental development in the "parlodel-baby" group. There is no consensus on the duration of continuous use of parlodel in women who do not want to get pregnant. The most serious complication associated with long-term use of the drug is considered to be the development of alveolar fibrosis, which is extremely rare in reality. The available experimental data on the activation of proliferative processes in the endometrium of rats with long-term use of the drug, although they cannot be uncritically transferred to clinical practice (the duration and dose of parlodel use in the experiment are incomparable with clinical conditions), still dictate the need for caution and periodic (for 3-4 months, after 12-16 months of treatment) breaks in parlodel intake with monitoring of prolactin levels. In the absence of endocrine-metabolic disorders and sexual dysfunctions in patients with persistent galactorrhea-amenorrhea syndrome who do not want to become pregnant, it is probably possible to limit ourselves to observation without treatment with parlodel, since there is a possibility of spontaneous remissions.

Microprolactinomas can be treated both by medication and by gentle surgical intervention - transsphenoidal microsurgical resection or cryodestruction. Some researchers prefer neurosurgical intervention, others, taking into account the extreme rarity of progressive growth of microadenomas during pregnancy and the antiproliferative effect of parlodel, as well as not excluding the possibility of pituitary insufficiency during surgical treatment, believe that women with microprolactinomas who want to become pregnant should be treated with parlodel before pregnancy and during pregnancy if signs of progressive tumor growth appear.

In case of macroadenomas with a tendency to rapid growth, preference is given to neurosurgical intervention. At the same time, preoperative treatment with parlodel in cases of invasive growth of an inoperable tumor can reduce invasion and make the tumor operable. As a rule, even after surgery, a patient with macroadenoma requires long-term therapy with parlodel. The high antimitotic activity of the drug in these tumors ensures growth retardation, reduction of cellular volume and fibrosis of prolactinomas.

In symptomatic forms of persistent galactorrhea-amenorrhea syndrome, Parlodel is used less frequently only when pathogenetic therapy is insufficiently effective and in combination with the latter (thyroid hormones in primary hypothyroidism, clomiphene in Stein-Leventhal syndrome). Indications for treatment with the drug for symptomatic persistent galactorrhea-amenorrhea syndrome against the background of somatic diseases have not been developed, but its use is allowed in case of liver and kidney failure, in particular for the correction of menometrorrhagia.

Of the domestically produced drugs, abergin (2-bromo-alpha-beta-ergocryptine mesylate) is successfully used for the treatment of patients with persistent galactorrhea-amenorrhea syndrome in an average daily dose of 4-16 mg.

New drugs for the treatment of hyperprolactinemic conditions include the long-acting dopamine agonists quinagolide and cabergoline.

Quinagolide (norprolac) is a non-ergot-containing dopamine mimetic belonging to the octabenzoquinoline class. The drug's selectivity for D2 receptors is due to the presence of the dopamine mimetic pharmacophore pyrroleethylamine. Quinagolide has virtually no interaction with other types of CNS and vascular receptors (D1-dopamine, serotonin and alpha-adrenergic), due to which the frequency and severity of side effects during its use are significantly lower than during treatment with bromocriptine. The biological activity of quinagolide is approximately 35 times higher than that of bromocriptine; it is effective in approximately 50% of patients resistant to previous therapy. The average therapeutic dose of the drug, depending on individual sensitivity, ranges from 50 to 150 mcg per day and is prescribed once, mainly in the evening.

Cabergoline (Dostinex) is an ergoline derivative characterized by high affinity and selectivity for dopamine D2 receptors. After a single dose, the prolactin-suppressing effect lasts for 21 days, which allows prescribing the drug 1-2 times a week at a dose of 0.25-2 mg, on average - 1 mg, in rare cases up to 4.5 mg. In terms of tolerability and effectiveness, cabergoline is significantly superior to bromocriptine, and in some cases quinagolide. Cabergoline and quinagolide, like bromocriptine, cause regression (up to complete disappearance) of prolactin-secreting pituitary adenomas. Preliminary results obtained in assessing the condition of children born due to the use of selective dopamine mimetics have shown that these drugs do not have a teratogenic effect. However, for the treatment of infertility due to hyperprolactinemia, due to the lack of information on the effects of long-acting dopamine agonists on the fetus, bromocriptine is currently preferred.

Forecast

Outpatient observation. With modern treatment methods, the prognosis for life and preservation of fertility is favorable. Patients with persistent galactorrhea-amenorrhea syndrome should be constantly monitored by an endocrinologist; in case of prolactinomas, observation by a neurosurgeon is also indicated. Depending on the state of the pituitary gland, dynamic MRI (preferably) or computed tomography (after 1-3 years), determination of prolactin levels (1-2 times a year), and an ophthalmologist and gynecologist examination once every six months are performed.

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Prevention of persistent galactorrhea-amenorrhea syndrome

Since the etiology and pathogenesis of various forms of persistent galactorrhea-amenorrhea syndrome have not been sufficiently studied, prevention of this disease has not been developed until recently. When the leading role of hyperprolactinemia in the genesis of the disease became known, the refusal to take drugs that increase the production of pituitary prolactin in patients with menstrual cycle disorders began to be recommended as a preventive measure. Sufficient replacement or corrective therapy of endocrine and non-endocrine diseases, against which hyperprolactinemia may develop, is also a preventive measure for persistent galactorrhea-amenorrhea syndrome.