Amenorrhea secondary

The reasons

Signs of secondary amenorrhea

Analyzes and surveys

Treatment of amenorrhea

Prognosis and prevention

ICD-10 Code N91.1 

Synonyms: amenorrhea, prolonged absence of menstruation. 

Secondary amenorrhea – the absence of menstruation for six months or more in women who are of reproductive age, as well as having an established menstrual cycle. 
The prevalence of the disease in a population ranges from 3 to 10%. 
In addition to the absence of menstruation, depending on the cause, there may be additional symptoms, such as hirsurtism (excessive hair growth), obesity, infertility, acne, hypertension. 
Treatment is based mainly on the use of hormonal drugs.

The reasons

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There are two classifications of secondary amenorrhea.

The first is the division into two groups: physiological and pathological.

  • Physiological amenorrhea is possible during pregnancy, during menopause, while breastfeeding a child.
  • Pathological secondary amenorrhea is all other options associated with improper functioning of the body.

The second classification is based on the causes of the development of secondary amenorrhea.

Who is at risk

Among the risk factors contributing to the development of secondary amenorrhea, are called:

  • the presence of excess weight
  • chronic diseases of the genital or endocrine organs;
  • uncompensated chronic diseases
  • strict diets
  • acute infections not only of the genital organs, but also of the organism as a whole.

Causes of the brain (central)

Psychogenic Amenorrhea

  • It develops as a result of strong nervous shocks, regular stresses, and is also associated with severe stress, a depressive state. For example, for many women, menstruation stopped during the war. This was called the term “wartime amenorrhea.” The body in the conditions of danger to life put the sexual instinct in the background. In the pituitary-hypothalamic system, the proper amount of gonadotropins did not stand out, the ovaries did not receive proper stimulation and did not function.

Pathological changes in the hypothalamus

  • Loss of body weight due to debilitating diets, chronic or acute illness, anorexia. Menstruation stops when the amount of adipose tissue drops below a critical minimum. Adipose tissue is normally an extravagant source of a small amount of estrogen. In addition, with fasting and adherence to a rigid diet, there is always psychological stress, stress, and neurosis. As a result, less ovarian-stimulating gonadotropic hormones are produced in the brain. Without proper stimulation, the ovaries do not produce enough sex hormones. 
  • Overly intense exercise.
  • Neuroexchange-endocrine syndrome (a disease with presumably genetic predisposition, characterized by impaired functioning of the adrenal glands and ovaries against the background of obesity).

Pathological changes in the pituitary gland

  • Hyperprolactinemia (excessive pituitary synthesis of the hormone prolactin due to hormone-active tumor or functional impairment). Prolactin is responsible for the growth of the mammary glands and the production of breast milk. Excess prolactin can occur with a tumor or damage to the pituitary gland, after neuroinfections, with thyroid pathology and other endocrine disorders, and with severe stress. With an excess of prolactin, suppression of gonadotropin production in the brain occurs. Further along a typical pattern: no gonadotropins – no ovarian stimulation – the ovaries do not synthesize enough sex steroids – no menstruation. 
  • The effect of tumor formations on the production of pituitary hormones.
  • Sheehan syndrome (pituitary cell death due to impaired blood flow in it during complicated labor or abortion).
  • Traumatic brain injury with damage to the pituitary gland.

Adrenal Disorders

  • Adrenogenital syndrome characterized by congenital adrenal hyperplasia.
  • Adrenal tumors that can synthesize male sex hormones (virilizing).
  • Syndrome or Itsenko-Cushing’s disease (long-term treatment with systemic glucocorticosteroids or increased secretion of adrenal cortisol).

Pathology in the ovaries

Exhausted Ovary Syndrome

  • cessation of ovarian function in women whose age has not reached the age of 40 years. Syndrome of depleted ovaries develops with the depletion in the ovaries of the stock of follicles and eggs. It is the follicle tissue during the maturation of the egg and in the process of ovulation secrete sex steroids in the ovaries every month. Normally, the stock of follicles ends at 45-55 years (time of menopause). With ovarian depletion, this happens prematurely. The reserve of follicles in this disease can be initially reduced (for example, genetically small is laid, or during prenatal development of a girl, toxins, poisons, adverse environmental effects have affected the pregnancy of the mother). When cysts are large in the ovaries, normal ovarian tissue can be replaced and the ovarian reserve is lost. The supply of eggs also decreases after operations with the removal of part of the ovary.

Resistant ovary syndrome

  • ovarian insensitivity to hormones produced by the hypothalamic-pituitary system. In the tissues of the ovary a sufficient number of follicles and eggs, but the ovary is not sensitive to stimulation by gonadotropins. There are assumptions about the autoimmune nature of this syndrome. The ovaries are resistant to the stimulation of their function by gonadotropins. Breakdown occurs at the receptor level for gonadotropins.

Polycystic Ovary Syndrome ( PCOS )

  • the presence on the ovaries of a large number of varying in size cysts that disrupt their normal function. It is characterized by a violation of ovulation (its absence or rare ovulation), scanty rare menses or amenorrhea, hyperandrogenism (an increase in the content of male sex hormones in a woman’s blood). Often (in about half the cases), polycystic ovary syndrome is accompanied by overweight and hyperinsulinemia. At the same time there are many follicles in the ovaries, but their maturation and release of the egg does not occur. In the primary form of PCOS, an excess of male sex hormones and insulin is a violation in the formation cycle of these hormones (breakdown and deficiency at the level of enzymes). In the secondary form of PCOS, an excess of male sex hormones cause other diseases of the endocrine organs (hypothyroidism, obesity, brain tumors with increased production of the hormones prolactin and ACTH, adrenal gland disease).

Gonad hyper retardation syndrome

  • develops after taking hormone drugs. Sometimes menstruation stops after the abolition of combined oral contraceptives, after treatment with hormonal drugs of certain groups in order to suppress active endometriosis and uterine fibroids. Usually, amenorrhea after hormone drugs are self-cured after a few months.

Other violations:

  • ovarian tumors and cysts , both benign and malignant;  
  • effects on chemotherapy or radiation therapy on the ovaries, consequence of surgery, artificially created menopause.

From the side of the uterus

Pathology of the uterus:

  • endometritis,
  • frequent abortive interventions
  • atresia of the cervical canal,
  • the presence of intrauterine adhesions.

Fusion (synechia) in the uterus – Asherman syndrome

  • In this case, the inner menstrual layer of the uterus is damaged. Women with Asherman’s syndrome always have a previous traumatic or inflammatory factor: traumatic abortion, frequent abortions, curettage, infectious complications after surgical manipulations with the development of endometritis.

Cervical Canal Fusion (atresia)

  • Occur after abortions, operations on the cervix (plastic, cervical amputation according to Sturmdorf), electroconization of the cervix with damage to the basal layer of the mucous membrane of the cervical canal. There are adhesions, the overgrowth of the cervical canal and the violation of the outflow of menstrual blood from the uterus. Menstruation can be scanty, smearing at the beginning and stop altogether with complete atresia of the canal.

Signs of secondary amenorrhea

The main symptom of secondary amenorrhea is the absence of menstruation for 6 months or more. However, often menstrual dysfunction is supplemented by other complaints, including:

  • decreased libido – sexual desire – a sign of androgen deficiency;
  • oily skin, acne, excessive hairiness, fat deposition on the abdomen and shoulder girdle are signs of excess androgens (male sex hormones);
  • a decrease in the size of the uterus and ovaries, a pale and dry mucous membrane in the vagina – signs of estrogen deficiency;
  • “Flushes” (as in menopause), sweating, palpitations, irritability, fatigue, skin aging – with a deficit of sex steroids;
  • galactorrhea – the appearance of discharge from the mammary glands, although the woman is not pregnant and does not breastfeed – with an excess of prolactin;
  • weight gain or, on the contrary, excessive weight loss in a short time without significant changes in diet and lifestyle (weight gain is observed in polycystic ovary syndrome, hyperprolactinemia and dysfunction of the thyroid gland);
  • the appearance on the skin of stretch marks (“stretch marks”);
  • depressions, mood swings;
  • fatigue, sleepiness or, on the contrary, worsening of sleep quality or insomnia;
  • puffiness of the face, dull and falling hair;
  • bouts of tachycardia, increased blood pressure;
  • headaches;
  • lower abdominal pain
  • in case of PCOS on examination by the gynecologist, the ovaries are palpated enlarged in volume, dense;
  • violation of visual fields and color perception – with a pituitary tumor.

Analyzes and surveys

Diagnosis of the presence of secondary amenorrhea is not difficult. It is much more difficult for doctors to determine the cause of the development of the disease in order to select the optimal correction options. The following tests and tests are usually assigned:

External and gynecological examination

Red Flags:

  • excess weight,
  • acne
  • girsurtism,
  • male figure with broad shoulders and narrow hips, etc.

For a complete diagnosis, a detailed history of the patient is important (the time of the first menarche, the regularity and duration of the cycle, the history of gynecological diseases, abortions, STDs).

Blood tests

Pregnancy testing (determination of the level of hCG in serum) is always performed with menstruation delays and irregular cycles.  

Evaluation of the hormonal status of the blood test:

  • LH,
  • FSH,
  • estradiol,
  • progesterone,
  • prolactin,
  • ACTH,
  • cortisol,
  • 17-OH progesterone,
  • DHEA-S,
  • testosterone.

Determining the concentration of thyroid hormones:

  • thyroxin (T4), 
  • thyroid stimulating hormone (TSH); 

The list of recommended hormones for evaluation may expand or narrow depending on the clinical picture in each particular case.

Additional methods:

  • Perform pharmacological tests (with progesterone, clomiphene, estrogen and gestagens). It consists in administering to the body certain doses of hormones with subsequent evaluation of the body’s response to them. The method helps to determine which hormones are lacking and at what level the deficit has arisen. In the case of a negative test, a menstrual-like reaction to the administration of the hormone does not occur. When positive, the patient responds to the introduction of hormones by bleeding from the uterus.
  • Analysis of genital infections (gonorrhea, trichomoniasis, syphilis, etc.).
  • Determination of blood glucose, test glucose tolerance if indicated, for example, polycystic ovary syndrome and obesity;   

Surveys

  • Hysteroscopy is a manipulation aimed at examining the uterus. Helps diagnose the presence of non-functioning endometrium. 
  • Ultrasound of the pelvic organs – allows you to identify synechia in the uterus, hematometer, reducing the size of the uterus and ovaries, cysts, no follicles in the ovaries, no endometrial growth in the uterus, no ovulation, polycystic and enlarged ovaries with a dense capsule. 
  • Diagnostic laparoscopy is an operation performed for diagnostic purposes, and is particularly informative in cases of secondary amenorrhea of ​​ovarian origin. Also, laparoscopy is indicated to clarify the diagnosis of emaciated or resistant ovarian syndrome, in case of infertility in a woman, and preparation for IVF.  
  • CT or MRI of the pituitary gland in case of suspected pathological changes in the work of this organ;
  • X-ray examination of the “Turkish saddle” with suspected pituitary tumor – prolactin.
  • Ultrasound of the kidneys , according to indications in / intravenous urography, is necessary for all patients with malformations of the reproductive system, often combined with kidney abnormalities.  
  • Ultrasound of the adrenal glands and thyroid gland.

Treatment of amenorrhea

Gynecologist-endocrinologist or gynecologist in tandem with an endocrinologist deals with amenorrhea therapy.

Treatment of a secondary form of amenorrhea depends on its origin. The main goal is to restore menstruation and, if possible, reproductive function.

Treatment may be directed to the immediate cause of the absence of menstruation, when it is known. If the cause of the disease is not clear or the disease itself is incurable, symptomatic therapy is prescribed.

If amenorrhea is caused by any chronic disease, first seek compensation for it, and then normalize the menstrual cycle.

The important points of treatment of amenorrhea also include:

  • Psychotherapy;
  • Physiotherapy
  • Healthy lifestyle, normalization of sleep and rest;
  • For weight loss, a high protein diet, counseling with a psychotherapist or psychiatrist with anorexia;
  • Amenorrhea caused by obesity is corrected with a low-carb diet, increased physical exertion;
  • In the psychogenic form – reducing stress effects, counseling with a psychologist, the use of sedatives.

Treatment methods

Medicamentous

Here, the gynecologist and the patient need to clearly know the purpose of the treatment:

  • restoration of menstrual function and normal hormonal levels in the absence of the desire to conceive or
  • recovery of menstruation, ovulation and childbirth.

Drugs and treatment tactics will be different in these situations.

Hormone replacement therapy

With resistant or ovarian syndrome

  • hormone replacement therapy (HRT) is shown. One of the easiest drugs to use for HRT in this case is femoston. The treatment is carried out before the age of the average menopause, according to indications and longer.

Hypothyroidism

  • hormone replacement therapy with thyroid hormones.

With hyperprolactinemia

  • “Bromkriptin”, “dostineks.”

Anti-androgenic drugs for PCOS and hyperandrogenism

Again, talking about two treatment goals.

  • reducing the severity of excess male sex hormones androgen
  • restoration of the ability to continue the race.

Achieving the first goal (for example, contraceptives) may precede the achievement of the second. KOC is divided into groups, including by the presence of anti-androgenic effect. To reduce the signs of excess androgens: oral contraceptives with antiandrogenic gestagens – ethinyl estradiol + cyproterone (“Diane-35”), ethinyl estradiol + dienogest (“Janine”), cyproterone (with the ineffectiveness of oral contraceptives).

Glucocorticoid drugs, for example, “dexamethasone” in a dose of 0.5 mg at night and the diuretic “spironolactone” or “veroshpiron” (100 mg 1–2 p. / Day) also have an antiandrogenic effect.

The effects of hormone therapy in relation to unwanted hair growth on the face and body, improving the condition of the skin and hair rarely occur quickly (improvement is observed no earlier than after 3-6 months). Often it is necessary to artificially remove hair: shaving, electrolysis, chemical hair removal.

Preparations for the stimulation of ovulation in the ovaries (for example, with PCOS)

  • Special schemes for the use of drugs “clomiphen” and “puregon” are used.

Stimulation of ovulation is used when the presence of menstruation and the absence of obesity. These drugs allow the follicle to mature in the ovaries. In some cases, pregnancy occurs independently after the induction of ovulation, and in other cases, stimulation makes it possible to pick up a mature egg for IVF.

Preparations for increasing insulin sensitivity in PCOS with obesity and hyperinsulinemia

  • “Siofor”, “metformin”

These drugs help patients with hyperinsulinemia in the fight against weight loss, reduce the density of the ovarian capsule. Weight loss and insulin levels in PCOS are necessary for a more favorable prognosis for conception and childbirth, as well as for the prevention of insulin-dependent diabetes mellitus.

Surgical treatment method

Surgical intervention is necessary in the case of synechiae in the uterus and fusion in the cervical canal.

The patient is dilated and dilated in the cervical canal in the hospital.

Synechias are destroyed by hysteroscopy and hysteroresectoscopy. These are vaginal surgeries, performed in the hospital under general anesthesia. After surgical removal of adhesions, a course of anti-inflammatory therapy (antibiotics, NSAIDs, means for preventing adhesive disease, enzymes, physical therapy) and hormone replacement therapy is prescribed.

Surgical treatment is also used in the absence of the effect of conservative treatment of PCOS. An operative laparoscopy is performed, and a dense capsule is made on the ovaries.

With hypertecosis and ovarian tumors secreting male sex hormones, excision of the ovaries is indicated.

Surgical treatment is also used in the case of growing hormone-producing pituitary tumors (for example, prolactinomas).

Assisted Reproductive Technology Method

(including IVF) – is in some cases the only way to become a mother to a woman.

Prognosis and prevention

Secondary amenorrhea with timely diagnosis and early treatment has a favorable prognosis. It is possible to restore both the menstruation and the reproductive function of the woman. The main complication of neglect is infertility, which can be difficult to correct and require the use of methods of reproductive technology.

The course and prognosis depend on the cause of amenorrhea. In hypothalamic-pituitary-related amenorrhea, the appearance of menstruation within 6 months was noted in 99% of patients, especially after the correction of body weight.

With appropriate timely correction of endocrine abnormalities in the body, the prognosis for the restoration of menstrual function is favorable. However, it must be remembered that treatment usually takes a long period, usually not less than six months.

The prognosis for childbirth depends on the cause of amenorrhea. Childbearing is not possible with advanced stages of ovarian depletion syndrome.

Independent conception and childbirth occur in patients after correction of hyperprolactinemia, hyperandrogenism, and thyroid hormones. With the help of ovulation stimulation, it is possible to induce pregnancy with PCOS and to take an egg cell for in vitro fertilization procedure with resistant ovary syndrome (with the cycle still saved). IVF with donor ovum and surrogate motherhood can help women with ovarian depletion syndrome.

Given the many factors that can provoke amenorrhea secondary type, specific prevention has not been developed.

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