Treatment of the syndrome of persistent galactorrhea-amenorrhea

Drug therapy occupies the main place in the treatment of all forms of the syndrome of persistent galactorrhea-amenorrhoea of hypothalamic-pituitary origin. With adenomas, it is complemented or competing with neurosurgical intervention or with radiation therapy. Until the 1970s, SSTA was considered incurable. However, this idea changed after the introduction into the medical practice of the semisynthetic alkaloid ergot, parlodel (bromocriptine), possessing the properties of the hypothalamic and pituitary agonist dopamine (DA-mimetic), and also capable of inhibiting the growth of prolactin in some patients by influencing the genetic apparatus of prolactotrophs.

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

With the "idiopathic" form of the syndrome of persistent galactorrhea-amenorrhea, treatment with parlodel for the restoration of fertility, normalization of the menstrual cycle, elimination of sexual, endocrine-metabolic and emotional-personality disorders associated with hyperprolactinemia is indicated. If the concept of a single genesis of the disease is correct with the transition of "idiopathic" forms to a microadenoma, the application of the parlodel can have a prophylactic value.

Parlodel is used according to the scheme, starting with 1.25 mg (0.5 tablets) 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 permissible. A single dose of parodela inhibits the secretion of prolactin on average by 12 hours. The drug reduces the level of prolactin to normal, reduces lac torus, restores a two-phase menstrual cycle. Ovulation occurs at 4-8 weeks of treatment. In those cases when infertility is caused only by hyperprolactinaemia, fertility recovery is possible in 75-90% of cases. On the background of treatment in most patients, weight loss decreases, headaches are less common; some note a decrease in sexual disorders, an improvement in the emotional background, a decrease in acne, sialorrhea, normalization of hair growth. Tolerability of the drug is relatively good, there may be side effects: nausea, constipation, nasal congestion, dizziness. They decrease or cease with the treatment, sometimes it is required 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, down to necrosis, and ultimately - cell involution and size reduction, and sometimes complete disappearance of the tumor. The effect of treatment depends on the degree of differentiation of the tumor - the more differentiated it is, the stronger. Refractory to the drug (i.e., no decrease in the level of prolactin 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 the level of prolactin, is not accompanied by ovulation, use a combination treatment with this drug in combination with gonadotropins or clomiphene.

Deviations in the development of children born from mothers who have received parlodel occur no more often than the average in the population. The drug has no abortive effect. Some researchers note the predominance of boys and the relatively accelerated mental development in the "parlodel-baby" group. There is no consensus on the duration of the continuous use of parlodel in women who do not want to become pregnant. The most serious complication associated with long-term use of the drug is the development of alveolar fibrosis, which is really rare. There are also experimental data on the activation of proliferative processes in the endometrium of rats with long-term administration of the drug, although they can not be uncritically transferred to clinical practice (duration and dose of application of parlodel in the experiment are not comparable with clinical conditions), nevertheless dictate the need for caution and periodic -4 months, after 12-16 months of treatment), interruptions in the administration of parlodel with the control of the level of prolactin. In the absence of endocrine-metabolic disorders and sexual disorders in those who do not want to become pregnant, patients with the syndrome of persistent galactorrhea-amenorrhea may probably be limited to observation without parodel treatment, since there is the possibility of spontaneous remissions.

Micropropactinoma can be treated with a medicamental method, or by sparing surgical intervention - transfenoid microsurgical resection or cryodestruction. Some researchers prefer neurosurgical intervention, others, considering the extreme rarity of progressive growth of the microaden during pregnancy and the antiproliferative effect of the parlodel, and also not excluding the possibility of pituitary insufficiency in operative treatment, believe that women who want to become pregnant with microproplatinomas should be treated with a parlodel prior to pregnancy and period of pregnancy with the appearance of signs of progressive growth of the tumor.

With macroadenomas with a tendency to rapid growth, preference is given to neurosurgical intervention. In this case, 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 surgical intervention of a patient with a macroadenoma, long-term parlodel therapy is required. High antimitotic activity of the drug with these tumors provides a slowdown in growth, a decrease in cell volume and fibrosis with prolactin.

With symptomatic forms of the syndrome of persistent galactorrhea-amenorrhea, parlodel is used less often only when the pathogenetic therapy is inadequate and in combination with the latter (thyroid hormones in primary hypothyroidism, clomiphene in the Stein-Levental syndrome). The indications for the treatment of symptomatic syndrome of persistent galactorrhea-amenorrhea against the background of somatic diseases have not been developed, but its use is allowed for liver and kidney failure, in particular, for correction of menometrorrhagia.

From domestic preparations for treatment of patients with the syndrome of persistent galactorrhea-amenorrhea, abergin (2-bromo-alpha-beta-ergocryptin mesylate) is successfully used in an average daily dose of 4-16 mg.

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

Quinagolide (norprolac) is an ergot-containing dopaminomimetic related to the class of octabenzoquinolines. The selectivity of the drug against D2 receptors is due to the presence of a dopaminomimetic pharmacophore pyrrolylethylamine. With the other types of receptors of the central nervous system and vessels (D1-dopamine, serotonin and alpha-adrenergic), quinagolide practically does not interact, so that the frequency and severity of side effects when used is significantly lower than with bromocriptine. Biological activity of quinagolide is approximately 35 times greater than that of bromocriptine, it is effective in about 50% of patients resistant to previous therapy. The average therapeutic dose of the drug, depending on the individual sensitivity is 50 to 150 mcg per day and is administered once, mainly in the evening.

Cabergoline (dostineks) is an ergoline derivative, characterized by high affinity and selectivity for D2 receptors of dopamine. After a single administration of prolactin, the suppressive effect persists for 21 days, which allows prescribing 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. For portability and efficacy, cabergoline significantly exceeds bromocriptine, and in some cases quinagolide. Cabergoline and quinagolide, like bromocriptine, cause regression (until complete disappearance) of prolactin secreting pituitary adenomas. Preliminary results obtained in assessing the condition of children born through the use of selective dopaminomimetics have shown that these drugs do not have a teratogenic effect. Nevertheless, for the treatment of infertility due to hyperprolactinemia, due to a lack of information on the effect of long-acting dopamine agonists on the fetus, bromocriptine is currently preferred.

Forecast

Dispensary observation. With modern methods of treatment, the prognosis for life and maintaining fertility is favorable. Patients with the syndrome of persistent galactorrhea-amenorrhea should be constantly monitored by an endocrinologist; with prolactinomas, the observation of a neurosurgeon is also shown. Depending on the condition of the pituitary gland, dynamic MP - tomography (preferably), or computed tomography (after 1-3 years), determination of prolactin level (1-2 times a year), and once a six months examination of the oculist and gynecologist are performed.

[1], [2], [3], [4], [5], [6], [7]

Prevention of the syndrome of persistent galactorrhea-amenorrhea

Since the etiology and pathogenesis of various forms of the syndrome of persistent galactorrhea-amenorrhea has not been adequately studied, until recently the prophylaxis of this disease has not been developed. When it became known about the leading role of hyperprolactinaemia in the genesis of the disease, as a prophylactic measure, it was recommended to refuse the use of drugs that increase the production of pituitary prolactin in patients with menstrual cycle disorders. Sufficient replacement or corrective therapy of endocrine and non-endocrine diseases, against which hyperprolactinemia may develop, is also a prophylaxis of the syndrome of persistent galactorrhea-amenorrhea.