Secondary amenorrhea is the cessation of menstruation for six months or more in women of reproductive age with an established menstrual cycle. The defining sign is the absence of menstruation for at least six months. Secondary amenorrhea can be accompanied by lower abdominal pain (with uterine form), mental disorders (with psychogenic form), obesity (with endocrine form), vegetative disorders (with ovarian form), etc. To determine the causes of amenorrhea, a general and gynecological examination, hormonal studies, ultrasound of the pelvic organs, radiography of the Turkish saddle, hysteroscopy and laparoscopy are performed. Treatment is aimed at correcting the factors that led to secondary amenorrhea.
N91.1 Secondary amenorrhea
Secondary amenorrhea is a violation of the menstrual cycle, characterized by the absence of menstruation for 6 months or longer. Unlike primary amenorrhea, the secondary form develops in previously menstruating women. At the age of 16-45 years, the frequency of secondary amenorrhea, unrelated to physiological causes (pregnancy, lactation, menopause), is 3-10% of cases. Secondary amenorrhea is one of the most difficult problems of reproductive health, since women with such a disorder always suffer from infertility. Spontaneous termination of menstruation indicates a serious dysfunction of the body, which may be in the plane of consideration of gynecology, endocrinology, psychiatry.
Among secondary amenorrhea, its true and false forms are distinguished. At the heart of true amenorrhea is a violation of the neuroendocrine regulation of the menstrual cycle. False amenorrhea is diagnosed with the preservation of the hormonal function of the ovaries and cyclic changes in the uterus; in this case, the absence of menstruation is associated with anatomical obstacles to the outflow of blood from the uterus and genital tract. With false amenorrhea, blood can accumulate in the fallopian tubes (hematosalpinx), uterus (hematometer) or in the vagina (hematocolpos).
Depending on the level of gonadotropic hormones regulating menstrual function, amenorrhea is divided into:
- hypogonadotropic, due to organic lesions of the pituitary gland or hypothalamus;
- hypergonadotropic, caused by disorders of ovarian function of genetic, enzyme, autoimmune or other etiology;
- normogonadotropic, caused by uterine pathology, PCOS, psychogenic factors, eating disorders, debilitating physical exertion, hyperprolactinemia.
Causes of secondary amenorrhea
The development of pathological secondary amenorrhea may be associated with various anatomical, genetic, biochemical, hormonal, neuropsychiatric factors. Taking into account the etiology and the level of lesion, secondary amenorrhea of hypothalamic, hypothalamic-pituitary, adrenal, ovarian, uterine, psychogenic genesis is distinguished.
Secondary hypothalamic amenorrhea is observed in women with functional disorders in the system “hypothalamus-pituitary gland-adrenal glands-ovaries” – the so-called hypothalamic syndrome. Such pathology develops under the influence of frequent viral diseases or chronic infections, excessive physical and mental stress, surgical interventions. Usually occurs in girls 1-3 years after menarche. The pathogenesis of hypothalamic syndrome is associated with hyperactivation of the sympathoadrenal system and stimulation of hypothalamic structures. Against this background, there is an increased secretion of LH, FSH, prolactin, ACTH, TSH, cortisol, aldosterone; a decrease in the level of estradiol and progesterone, STH. In the future, as the sympathoadrenal system is depleted, the activity of the hypothalamic-pituitary-adrenal system also decreases, which is accompanied by secondary amenorrhea.
Disorders in the hypothalamus can also occur against the background of significant weight loss due to a low-calorie diet or anorexia nervosa. It is known that even the loss of 10-15% of weight from the physiological and age norm can cause symptoms of secondary amenorrhea, and a weight loss of less than 46 kg leads to insensitivity of the pituitary gland to stimulation by gonadoliberins. Another cause of hypothalamic amenorrhea may be a false pregnancy. In this syndrome, there is an increased secretion of LH and prolactin with simultaneous inhibition of FSH synthesis.
Secondary amenorrhea of hypothalamic-pituitary genesis is most often associated with functional and organic hyperprolactinemia. An increase in prolactin production is accompanied by a decrease in the synthesis of gonadotropins, which causes the cessation of menstruation. Functional hyperprolactinemia can develop against the background of hypothyroidism, prolonged lactation, stress, abortions, long-term use of psychotropic, hormonal drugs, COCs. The causes of organic hyperprolactinemia may be tumors of the pituitary gland (prolactinoma). Disorders of the hypothalamic-pituitary regulation of the menstrual cycle are noted in Sheehan syndrome, pituitary adenoma, TBI, neuroinfections.
The adrenal variant of secondary amenorrhea occurs in adrenogenital syndrome (congenital adrenal hyperplasia), virilizing tumors of the adrenal glands, hyperplasia of the adrenal cortex, Itsenko-Cushing syndrome. Ovarian forms are observed in ovarian depletion syndrome, resistant ovarian syndrome, PCOS, ovarian tumors, oophoritis, artificial menopause induced by surgery or radiation therapy.
Uterine forms of secondary amenorrhea are most often associated with inflammatory or traumatic damage to the endometrium. The destruction of the endometrium can occur due to endometritis of tuberculous or gonorrheal etiology, repeated abortions and diagnostic curettage, endometrial ablation. At the same time, as a result of damage to the basal layer of the uterus, cyclic transformation of the endometrium in response to hormonal stimulation and its desquamation does not occur. Less common among uterine amenorrhea factors are Ascherman syndrome, cervical canal atresia due to electroconization of the cervix.
Psychogenic, or stress-amenorrhea accounts for about 10% of cases among other forms of the disorder. It can be provoked by acute or chronic emotional and mental injuries. Stress amenorrhea often occurs in women during periods of armed conflict and social disasters, therefore it is often defined as “wartime amenorrhea”. The stressful effect on the body causes the release of a large amount of ACTH, neurotransmitters that block the secretion of gonadotropin-releasing factor, which leads to a violation of the production of gonadotropins (FSH and LH) by the pituitary gland and a decrease in the synthesis of sex hormones by the ovaries.
Forms of secondary amenorrhea
Regardless of the cause of secondary amenorrhea, it is common for all forms to stop menstrual bleeding, which previously occurred more or less regularly, and infertility. The criterion is considered to be the absence of monthly periods for 6 or more consecutive months. The remaining symptoms are variable and depend on the form of secondary amenorrhea.
Psychogenic amenorrhea is additionally accompanied by asthenoneurotic, depressive or hypochondriac syndromes. Patients note increased fatigue, anxiety, sleep disorders, a tendency to depression, decreased libido. Tachycardia, dry skin, constipation may bother. Menstruation stops suddenly, there is no period of oligomenorrhea.
Amenorrhea on the background of weight loss is accompanied by a noticeable weight deficit; during a medical examination, hypoplasia of the mammary glands and genitals is detected. Other signs of malnutrition include arterial hypotension, bradycardia, hypothermia, hypoglycemia, constipation. Appetite is reduced, persistent aversion to food and cachexia may develop, indicating the onset of anorexia.
Secondary amenorrhea in hypothalamic syndrome is combined with early puberty, obesity, hirsutism, the presence of acne and striae on the skin, vegetative-vascular dystonia. Amenorrhea associated with hyperprolactinemia is characterized by spontaneous galactorrhea. Frequent complaints of cephalgia, dizziness, hypertension. There are psychoemotional disorders: mood variability, irritability, depressive reactions.
With ovarian forms of secondary amenorrhea, the disappearance of menstruation is often preceded by a period of oligomenorrhea. The patients have a history of timely onset of menarche and often normal menstrual function. With resistant ovarian syndrome, menstruation stops before the age of 35, but there are no vegetative-vascular disorders characteristic of premature menopause. Amenorrhea associated with ovarian depletion syndrome, on the contrary, is accompanied by hot flashes, facial hyperemia, sweating, headaches.
The defining symptom of false amenorrhea is spastic pain in the lower abdomen caused by a violation of the outflow of menstrual blood. With chronic endometritis, menstrual cycle disorders develop gradually: over time, the intensity and duration of menstruation decreases until complete cessation.
Secondary amenorrhea is diagnosed on the basis of anamnesis and clinical picture. However, a more difficult task for gynecologists, endocrinologists, neurologists, psychotherapists and other specialists is the differential diagnosis of the form of amenorrhea and the determination of its causes. When determining the gynecological status of the patient, the age of menarche, the nature of menstruation in the past, obstetric history, gynecological and extragenital diseases, operations and injuries, heredity, nutrition, stress susceptibility and other factors affecting menstrual function are taken into account.
Mandatory for secondary amenorrhea are examination on a chair, functional tests (pupil symptom, basal temperature measurement, colpocytology), colposcopy, ultrasound of the pelvic organs. Within the framework of differential diagnostics, pharmacological tests are widely used: with progesterone, estrogens and progestogens, clomiphene, gonadotropins. To detect intrauterine pathology, hysterosalpingography and hysteroscopy are performed. In ovarian forms of secondary amenorrhea, diagnostic laparoscopy is informative.
In order to identify hormonal disorders, a study of TSH, T4, insulin, LH and FSH, estradiol, progesterone, testosterone, prolactin, ACTH, cortisol and other hormones is shown, taking into account the suspected variant of secondary amenorrhea. If a pituitary pathology is suspected, an X-ray of the Turkish saddle is performed; according to the indications, a CT or MRI of the pituitary gland is performed. The examination plan includes an ophthalmologist’s consultation with an examination of the fundus (ophthalmoscopy) and a study of the fields of vision.
Treatment of secondary amenorrhea
Treatment options for secondary amenorrhea are closely related to its form. Therapy is aimed at eliminating the causes of amenorrhea, if possible – restoring menstrual and reproductive functions.
Secondary amenorrhea caused by weight deficiency or anorexia is treated together with psychotherapists and nutritionists. Patients are prescribed a high-calorie diet with frequent fractional nutrition, sedatives, multivitamins, psychotherapy. If there is no spontaneous recovery of the menstrual cycle against this background, hormone therapy is prescribed for 4-6 months. Patients with a psychogenic form of amenorrhea are recommended to exclude provoking factors, normalize working and rest conditions. Physiotherapy courses are shown: endonasal electrophoresis, balneotherapy.
If the cause of amenorrhea is hypothyroidism, thyroid hormones are used in long courses. Patients with hyperprolactinemia are indicated to take bromocriptine, cabergoline and their analogues. Detection of pituitary macroadenoma based on the results of the examination is the basis for surgical or radiation treatment.
Therapy of ovarian forms of secondary amenorrhea consists in the appointment of cyclic hormone therapy, low-dose COCs. If an ovarian tumor is detected, an ovariectomy or adnexectomy (removal of appendages) is required. With atresia of the cervical canal, its augmentation is performed. The treatment of synechiae of the uterine cavity is operative, using hysteroresectoscopy. In infectious processes, the appointment of etiotropic antibacterial therapy is indicated. In the future, to improve metabolic processes in the uterus, it is advisable to conduct physiotherapy procedures – ultrasound, electrophoresis, diathermy on the pelvic area.
In most cases, with the help of properly organized treatment, it is possible to achieve the resumption of menstruation. The prognosis in terms of restoring reproductive function depends on the form of secondary amenorrhea. If infertility persists, a woman is recommended to consult a reproductologist. Modern reproductive technologies allow for in vitro fertilization (using the IMSI or ICSI method), if necessary using donor sperm, donor egg or donor embryo. To increase the chances of pregnancy after artificial insemination and a successful embryological stage, cryopreservation of embryos is performed with their subsequent defrosting and planting in the patient’s uterus. Chronic miscarriage of pregnancy is an indication for the use of surrogacy.