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Persistent galactorrhea-amenorrhea syndrome - Information review
Last reviewed: 04.07.2025
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Persistent galactorrhea-amenorrhea syndrome is a characteristic clinical symptom complex that develops in women due to a long-term increase in prolactin secretion. In rare cases, a similar symptom complex develops with a normal serum level of prolactin, which has an excessively high biological activity. In men, chronic hypersecretion of prolactin occurs much less frequently than in women, and is accompanied by the development of infertility, impotence, gynecomastia, sometimes with lactorrhea.
Persistent galactorrhea-amenorrhea syndrome was considered an extremely rare disease for a long time. The identification of different forms of the syndrome depending on the presence or absence of a radiologically detectable adenoma or on previous pregnancy and childbirth (Forbes-Albright, Chiari-Frommel, Ayumada-Argonza-del Castillo syndromes) exacerbated the erroneous assumption of its rarity.
In the early 1970s, thanks to the development of a radioimmune method for determining prolactin, as well as the introduction of polytomography of the sella turcica, it became clear that chronic hyperproduction of pituitary prolactin accompanies every third case of female infertility and can be both the main pathogenetic link in an independent hypothalamic-pituitary disease, and a consequence of a number of endocrine and non-endocrine diseases with secondary involvement of the hypothalamus and pituitary gland in the process.
The term "persistent galactorrhea-amenorrhea syndrome" cannot be considered to fully reflect the essence of the disease. There are no statistical data on the actual frequency of hyperprolactinemic syndrome and its specific form - persistent galactorrhea-amenorrhea syndrome. In the last twenty years, the number of diagnosed cases has increased significantly. Mass screening undertaken in 1986 by K. Miyai et al. (10,550 residents of Japan who did not present any complaints were examined) revealed 5 patients with prolactinoma, 13 people with drug-induced hyperprolactinemia and 1 patient with "empty" sella turcica syndrome. It can be assumed that the frequency of prolactinomas, at least in the Japanese population, exceeds 1:2800 in men and 1:1050 in women. Autopsy data reveal an even higher frequency of asymptomatic prolactinomas, but it is unclear whether these lesions have any clinical significance.
Persistent galactorrhea-amenorrhea syndrome is a disease of young women, and is extremely rare in childhood and old age. The average age of patients is 27-28 years. The disease is diagnosed much less frequently in men, usually at the age of 25-40 years, although cases of hyperprolactinemia in adolescents and old people have been described.
Causes and pathogenesis of persistent galactorrhea-amenorrhea syndrome
The genesis of pathological hyperprolactinemia is heterogeneous. It is assumed that the syndrome of persistent galactorrhea-amenorrhea, caused by primary damage to the hypothalamic-pituitary system, is based on a violation of the tonic dopaminergic inhibitory control of prolactin secretion.
The concept of primary hypothalamic genesis suggests that a decrease or absence of the inhibitory effect of the hypothalamus on prolactin secretion leads first to hyperplasia of prolactotrophs and then to the formation of pituitary prolactinomas. The possibility of persistence of hyperplasia or microprolactinoma that does not transform into a subsequent stage of the disease (i.e., into macroprolactinoma - a tumor extending beyond the sella turcica) is allowed. Currently, the dominant hypothesis is a primary pituitary organic lesion (adenoma), not detected at early stages by conventional methods. This adenoma is monoclonal and is the result of a spontaneous or induced mutation; releasing hormones, numerous growth factors (transforming growth factor-alpha, fibroblast growth factor, etc.) and imbalance between regulatory influences can act as promoters of tumor growth. In this case, excess prolactin leads to the production of excess dopamine by neurons of the tuberoinfundibular system.
Causes and pathogenesis of persistent galactorrhea-amenorrhea syndrome
[ Symptoms of persistent galactorrhea-amenorrhea syndrome
The most common reason for women with persistent galactorrhea-amenorrhea syndrome to seek medical attention is menstrual irregularities and/or infertility. The former varies from opso-oligomenorrhea to amenorrhea, most often secondary. Polymenorrhea is not typical of hyperprolactinemic syndrome, with the exception of its symptomatic forms associated with primary hypothyroidism. Approximately every fifth patient reports that menstruation has been irregular since menarche, the onset of which is somewhat delayed in many patients. Subsequently, menstrual irregularities are especially clearly detected during chronic stress situations (exam sessions, long-term illnesses, conflict situations). The development of amenorrhea often coincides in time with the onset of sexual activity, discontinuation of previously used oral contraceptives, termination of pregnancy, childbirth, insertion of intrauterine contraceptives, or surgery. As a rule, patients with persistent galactorrhea-amenorrhea syndrome are more concerned about menstrual irregularities and/or infertility.
Galactorrhea is rarely the first symptom of persistent galactorrhea-amenorrhea syndrome (in no more than 20% of patients) and even more rarely the main complaint. Sometimes, even with significantly increased prolactin levels, it is absent.
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Diagnosis and differential diagnosis of persistent galactorrhea-amenorrhea syndrome
If the diagnosis of typical forms of persistent galactorrhea-amenorrhea syndrome seems quite simple today, then the differential diagnosis of “erased”, “incomplete” forms from symptomatic forms of persistent galactorrhea-amenorrhea syndrome, as well as from various unclearly defined and poorly studied clinical syndromes, in which galactorrhea develops against the background of normal serum prolactin levels and its correction does not change the course of the underlying disease and does not alleviate the patient’s condition, is very complex.
Laboratory and instrumental examination required to confirm the presence of persistent galactorrhea-amenorrhea syndrome consists of 4 stages:
- confirmation of the presence of hyperprolactinemia by determining the serum level of prolactin;
- exclusion of symptomatic forms of persistent galactorrhea-amenorrhea syndrome (determination of the functional state of the thyroid gland, exclusion of Stein-Leventhal syndrome, liver and kidney failure, neuroreflex and drug effects, etc.);
- clarification of the condition of the adenohypophysis and hypothalamus (X-ray of the skull, computed tomography or magnetic resonance imaging of the head, with additional contrast if necessary), carotid angiography;
- clarification of the state of various organs and systems against the background of chronic hyperprolactinemia (determination of the level of gonadotropins, estrogens, DHEA sulfate, study of the state of carbohydrate and fat metabolism, the skeletal system, etc.).
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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 with remote 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.