Follicle persistence is a hormone—related disorder of menstrual function, in which folliculogenesis is disrupted, ovulation is absent and the functioning of the dominant follicular formation is preserved. It is manifested by opsomenorrhea, spaniomenorrhea, menorrhagia, infertility, abdominal pain. It is diagnosed using folliculometry, ultrasound of the pelvic organs, determination of estrogen levels, progesterone, FSH, LH, histological examination of the endometrium. The main treatment regimens provide for the appointment of hormonal agents — progestogens, combinations of estrogens with progestins, antiestrogenic drugs, LH analogues.
Normally, folliculogenesis is regulated by follicle-stimulating and luteinizing hormones of the anterior pituitary gland. In the first phase of the menstrual cycle, under the influence of FSH, a dominant follicle is formed in the ovarian tissue, in the second, a mature oocyte under the influence of LH leaves the ovary and enters the fallopian tube. With insufficient concentration of LH (luteotropin, lutropin), ovulation does not occur, the mature follicle continues to function, releasing a large amount of estrogens.
The clinical picture of the disorder caused by prolonged follicle persistence in the premenopausal period was first described in 1915 by the German obstetrician-gynecologist Robert Schroeder. Subsequently, the disease was called hemorrhagic metropathy or Schroeder’s disease. Later, a variant of ovulation disorder with short-term rhythmic persistence of follicular tissue was identified, characteristic of patients of adolescent and reproductive age.
The key etiological factor causing the disorder is a violation of the secretion of luteinizing hormone by the pituitary gland. Hormonal failure can occur in any link of the hypothalamic-pituitary system. The main causes of isolated inhibition of LH synthesis with a sufficient level of estrogens, characteristic of follicular persistence, are:
- Diseases of the hypothalamus and pituitary gland. More often, hypothalamic-pituitary pathology is accompanied by a violation of the secretion of several releasing factors or tropic hormones. However, in some tumors of the pituitary gland and hypothalamus, other brain pathology (meningitis, encephalitis, stroke, autoimmune and radiation damage), isolated suppression of luteotropin secretion is possible.
- Age-related hormonal restructuring. The formation of mechanisms of humoral regulation in adolescence and after childbirth, their imbalance during menopause may be accompanied by non-synchronous production of lyuliberin (GnRH), LH and FSH. In addition, against the background of involutive atrophy of the epiphysis, the production of melatonin decreases, which affects the normal secretion of luteinizing hormone.
- Taking pharmaceutical drugs. LH synthesis can be disrupted when taking medications that affect the pituitary gland — progestins, hormone antagonists, cardiac glycosides, phenothiazines. Temporary hormonal failure with inhibition of luteotropin secretion occurs after exposure to high doses of estrogens that are part of monopreparations or combined oral contraceptives.
- Stressful loads. With prolonged hard work, constant emotional experiences, the level of ACTH increases. Under the influence of adrenocorticotropin, lutropin secretion decreases. Due to the high energy consumption during stress, the release of GnRH, necessary for the synthesis of LH, is disrupted. The same mechanism underlies anovulation in anorexia nervosa and sports amenorrhea.
The basis of follicle persistence is the absence of the luteal phase of the menstrual cycle. Due to insufficient concentration of luteinizing hormone, the mature egg remains in the ovary, further physiological changes in the follicular tissue do not occur, active secretion of estrogens persists with insufficient progesterone levels. Against the background of absolute hyperestrogenism, proliferative processes continue in the mucous layer of the uterus. Hyperplasia of the endometrium develops, which does not undergo secretory transformation. With a significant overgrowth of the inner uterine layer, the trophic cells are disrupted, blood vessels are thrombosed, necrosis and desquamation begin. As a rule, the endometrium is rejected in separate areas, which can cause profuse prolonged bleeding.
The criterion for systematization of clinical variants of follicle persistence is the period during which the hormonal activity of the follicular tissue persists. This approach takes into account the features of the etiopathogenesis of possible variants of the disease. With this in mind , specialists in the field of gynecology have identified two main forms of the disorder:
- Short-term rhythmic persistence. It can occur at any age under the influence of factors that cause an imbalance in the secretion of GnRH, LH, FSH (diseases, stress, stress, medication). The mature follicle actively functions for 20-40 days, after which menstrual-like uterine bleeding begins.
- Long-term persistence (Schroeder disease). It usually develops in premenopause against the background of involutive changes in the humoral regulation of reproductive function, primarily circadian disorders due to age-related atrophy of the epiphysis. Prolonged persistence ends with follicle atresia and profuse bleeding.
Symptoms of follicle persistence
The main manifestation of the disorder is anovulatory dysfunctional uterine bleeding. Metrorrhagia are irregular. The intermenstrual interval exceeds 35 days, often reaches 6-8 weeks or more. In extreme cases, menstrual-like bleeding occurs 2-4 times a year. With short-term follicular persistence, the intensity of bloody discharge may not differ from normal menstruation, with prolonged bleeding profuse, prolonged (more than 7 days). Women of reproductive age complain of infertility. Some patients have pulling pains on the right or left in the lower abdomen.
The accumulation of secretions in the cavity of a long-lasting persistent dominant follicle can lead to the formation, progression and rupture of an ovarian cyst. In some cases, cystic formations reach 5 cm in diameter and are accompanied by persistent pain syndrome. Against the background of abundant metroragia, secondary iron deficiency anemia often occurs. The constant persistence of follicles is accompanied by significant hyperestrogenism, provoking malignant degeneration of the endometrium, the development of endometriosis, cervical dysplasia, uterine fibroids, cystic fibrotic mastopathy, breast cancer.
Examination to exclude the persistence of the follicle is prescribed to patients with complaints of menstrual irregularities, constant delays of menstruation, inability to get pregnant. Since the symptoms of the disorder are not pathognomonic and can be observed in other gynecological diseases, methods are recommended for diagnosis to identify the non-ovulated dominant follicle and characteristic hormonal changes:
- Monitoring of folliculogenesis. Folliculometry is the gold standard in the diagnosis of follicular persistence. Almost before the onset of menstrual-like secretions, one or more dominant follicles with sizes of 18-24 mm or more remain in the ovary. There are no signs of ovulation — the yellow body does not develop, there is no free fluid in the retro-uterine space.
- Determination of the level of sex hormones. There is no luteal phase of the ovarian cycle: a high concentration of estradiol is constantly maintained, the progesterone content in the blood does not increase in the second half of the intermenstrual cycle, the level of pregnanediol in the urine is reduced. The content of FSH is increased, luteinizing hormone is reduced, the secretion of gonadotropins is irregular.
- Ultrasound of the pelvic organs. Ultrasound examination reveals changes characteristic of hyperestrogenism: the endometrium is hyperplasized, the uterus is enlarged in size. In patients with rhythmic persistence, small-cystic degeneration of ovarian tissue is noted, with Schroeder’s disease, polycystic degeneration of the ovaries with an increase in their size is possible.
- Histological examination of endometrial biopsy. The biological material obtained by hysteroscopy or diagnostic curettage of the uterus reveals signs of excessive proliferation, various variants of endometrial hyperplasia — glandular-cystic, adenomatous, polypous, atypical. Possible dysplasia of the mucous membrane.
As an additional method, colposcopy is shown, revealing hyperestrogenic changes in the cervix — hypertrophy with hyperplasia, pseudoerosion, endocervicitis, cervicitis, leukoplakia, dysplasia. In a general blood test, a decrease in the levels of erythrocytes and hemoglobin is often determined. Follicular persistence is differentiated with pregnancy, early menopause, other causes of anovulation and dysfunctional uterine bleeding — adrenogenital syndrome, polycystic ovaries, ovarian dysfunction in oophoritis, adnexitis, ovarian tissue tumors, etc. According to the indications, the patient is consulted by an endocrinologist, a neurosurgeon, an oncologist.
Treatment of follicle persistence
Patients are shown conservative therapy with hormonal correction of the disorder. The main goals of treatment are to restore the normal menstrual cycle, fertility and prevention of possible complications of an imbalance of sex hormones, especially hyperestrogenism. To eliminate follicular persistence , the most effective:
- Combined oral contraceptives. The appointment of modern estrogen-progestogenic drugs restores the normal cyclic content of sex hormones in the blood in the absence of ovulation. After the cancellation of the COC, a rapid normalization of the menstrual cycle is possible.
- Gestagens. Progestins block excessive proliferation and ensure normal secretory transformation of the endometrium, reducing the risk of hyperestrogenic carcinogenesis. Gestational therapy is carried out when hyperproliferative processes are detected in the uterine mucosa.
- Cyclic estrogen-progestogenic therapy. Taking monopreparations according to the scheme of the physiological menstrual cycle allows you to more accurately control the level of sex hormones. The principle of operation of such hormone therapy is similar to the use of COC, but differs in greater variability.
- Cyclic therapy with HCG and progestins. It serves as an alternative to estrogen-progestogenic regimens with high estrogenic saturation of the body. Analogues of chorionic gonadotropin have a luteinizing effect, are able to stimulate ovulation, and progestins transform the endometrium.
- GnRH agonists. They affect the key pathogenetic link of the disorder — a violation of hypothalamic-pituitary metabolism. Especially effective in hyperestrogenism. The advantage of GnRH agonists is the selectivity of action depending on the level of estrogens.
- Analogues of luteinizing hormone. They make up for the lack of lutropin in the body, stimulate ovulation, and support the development of the corpus luteum. Taking into account the possible increase in follicular secretion with persistence, they are used with caution under the control of hormonal background.
Symptomatic treatment usually includes the use of antianemic drugs, medical and surgical hemostasis in case of heavy bleeding (the use of uterotonics, antihemorrhagic and hemostatic agents, monophasic COCs, therapeutic and diagnostic curettage of the uterine cavity). Drug therapy is supplemented with diet correction with an increase in the amount of proteins, vitamins, trace elements, vitamin therapy, adaptogens. Physiotherapy procedures are prescribed: electrophoresis with copper and zinc sulfates, cervical-facial galvanization, endonasal electrophoresis with vitamin B1 and novocaine, ultrasound exposure to the uterus, laser therapy, gynecological massage.
Prognosis and prevention
Timely detection of follicle persistence and the use of modern methods of hormone therapy in most cases allows you to restore menstrual and reproductive functions, prevent possible hyperestrogenic complications. Primary prevention is aimed at eliminating physical and emotional overload, compliance with the principles of rational nutrition, adequate rest, the use of hormonal contraception only taking into account the recommendations of an obstetrician-gynecologist, limited prescription of other drugs that can disrupt the menstrual cycle.