Anovulatory menstrual cycle in women

In the absence of an ovulatory phase in a woman's menstrual cycle, it is defined as an anovulatory cycle.

In ICD-10, the code N97.0 has infertility associated with anovulation in women. And this is logical, since the absence of ovulation itself is not considered a disease, but a sign of the pathology of the female reproductive system that occurs in various conditions and diseases. 

Epidemiology

According to statistics, 15% of women of reproductive age can have a menstrual cycle without ovulation; 50% of adolescent girls have anovulatory cycles in the first two years after the onset of menstruation.

In young women, 75-90% of cases of anovulation are the result of polycystic ovary syndrome; more than 13% of cases are due to hyperprolactinemia. In 7.5% of cases, idiopathic chronic anovulation is observed. [1],  [2], [3]

Almost 30% of cases of infertility are caused by the anovulatory cycle. [4]

Causes anovulatory cycle

The ovulatory and anovulatory cycles differ fundamentally: the first is a  normal menstrual cycle  with alternation of all phases (follicular or follicular, ovulatory and luteal); the second is abnormal, without the release of a mature oocyte from the follicle, that is, without ovulation, without the formation and involution of the corpus luteum and the release of luteinizing hormone from the pituitary gland.

It should be borne in mind that the anovulatory cycle can be not only pathological, but also physiological. In particular, it occurs during the first two years after menarche in girls; with a sharp change in the climatic zone of residence or severe stress; during lactation after childbirth; after miscarriage or stopping birth control pills, and after 45 years - due to fluctuations in hormone levels before menopause.

The main causes of the pathological anovulatory cycle are hormonal disorders, which, in turn, can be caused by:

• polycystic ovary syndrome  (PCOS);
• dysfunction of the ovaries in the presence of their chronic inflammation -  oophoritis ;
• d hyperanlrogenism ;
• excessive production of prolactin by the pituitary gland -  hyperprolactinemia ;
• hyperestrogenism  or, conversely,  estrogen deficiency ;
• dysfunction of the hypothalamic-pituitary system -  gonadotropic insufficiency ;
• imbalance of thyroid-stimulating hormones (thyroxine and triiodothyronine) with hyper or hypothyroidism;
• dysfunction of the adrenal cortex (hypocorticism), including with its hormonally active tumor -  androsteroma .

In addition, exceeding the quantitative norm of follicles - multifollicular ovaries can also cause anovulatory cycle, since the  multifollicular structure of the ovaries  prevents follicle maturation and, in addition, often leads to PCOS and associated hormonal imbalances. [5]

In more detail in the publication -  Causes, symptoms and diagnosis of anovulation

Depending on the etiology and hormonal state, experts distinguish normogonadotropic normoestrogenic, hypergonadotropic hypoestrogenic and hypogonadotropic hypoestrogenic types of anovulatory cycle. [6]

Risk factors

Factors that significantly increase the risk of a cycle without ovulation include:

• long-term use of oral contraceptives;
• hereditary or acquired insulin resistance, leading to metabolic syndrome - with an increase in the production of adrenocorticotropic hormone (ACTH) by the pituitary gland and hyperandrogenism;
• overweight or underweight;
• the impact on the hormonal background of frequent stress;
• excessive physical exertion (menstrual irregularities and amenorrhea are included in the so-called triad of female athletes);
• diseases of the uterus (endometriosis, fibroids, etc.);
• tumor formations of the ovaries, thyroid and parathyroid glands, pituitary gland or hypothalamus;
• adrenal insufficiency.

Pathogenesis

For all of the above reasons, including polycystic ovary syndrome with damage to their follicular apparatus, the pathogenesis of the absence of ovulation is associated with the fact that hormonal homeostasis is disturbed - the natural balance of sex steroids and gonadotropins: estradiol and estrone, androstenedione and testosterone, luteotropin luteotropin and follite-lithropiruin - LH and FSH), progesterone, prolactin, gonadotropin-releasing hormone, which are produced by the ovaries and the corpus luteum, the adrenal cortex and the hypothalamic-pituitary system. [7],  [8], [9]

A more detailed understanding of the positive and negative relationships of sex and gonadotropic hormones will help publications:

• Menstrual function
• Hormonal regulation of the menstrual cycle
• Monthly cyclical changes in the female reproductive system
• Impaired ovulation

Symptoms anovulatory cycle

With anovulation, the first signs are manifested by  irregularities in the menstrual cycle , when it is shorter than 21 days or longer than 35 days, or the duration of the cycles changes from month to month. Although menstruation during anovulatory cycle (which many gynecologists consider menstrual bleeding) may be less regular and more prolonged. About 20% of women have no periods, that is, amenorrhea is observed  , and in 40% of cases, rare and short menstruation is observed (if the intervals between menstruation increase by more than 35 days, this is defined as oligomenorrhea). [10]

In addition, the following symptoms are noted:

• in the second phase, the basal temperature does not increase during the anovulatory cycle;
• there are spotting in the middle of the cycle;
• weight gain and facial hair growth (often associated with PCOS and hypocorticism);
• severe bleeding may occur during the anovulatory cycle, which is associated with insufficient levels of FSH and LH and a  deficiency of progesterone  - hormones that neutralize the effect of estradiol on the uterine mucosa. This type of bleeding is called estrogen breakthrough or metrorrhagia and can be confused with menstruation.
• mucous secretion of the cervix - cervical mucus in the anovulatory cycle may become more abundant and liquid for several days, which indicates an increase in estrogen levels in anticipation of ovulation, but then it becomes thick again.

If the anovulatory cycle also hurts the chest, then this is an indicator of low progesterone levels. In about 20% of women with ovulation problems, breast tenderness (mastodynia) is not observed.

But the endometrium in the anovulatory cycle of a chronic nature, especially in women with PCOS, undergoes hyperplasia, that is, overgrowth and thickening - due to the lack of an inhibitory effect of progesterone on the stimulation of the mucous membrane of the uterine cavity by estrogen.

Complications and consequences

The main consequences and complications of a cycle without an ovulatory phase include:

• infertility, since pregnancy does not occur after the anovulatory cycle (and even when trying to get pregnant with IVF, a donor egg is used);
• early perimenopause and menopause;
• anemia;
• decreased bone density;
• cancerous degeneration of the endometrium.

Diagnostics anovulatory cycle

It seems that in the absence of menstruation or irregularities in their periodicity, the diagnosis of anovulatory cycle is very simple. But this is not the case in all cases. [11]

To diagnose the anovulatory cycle, women take blood tests for the level of estrogen, progesterone, luteinizing and follicle-stimulating hormones, prolactin, 17a-hydroxyprogesterone, dihydrotestosterone, ACTH, thyroid hormones, insulin. [12]

Instrumental diagnostics is carried out:

• x-ray of the uterus and ovaries ;
• Ultrasound of the pelvic organs and uterus .

When conducting transvaginal ultrasound with high resolution, the anovulatory cycle, ultrasound signs are determined by the absence of visualization of protrusion in the cortical substance of the dominant (preovular) follicle covering the ovary and vascularization of its wall (perifollicular vascular perfusion). 

The task that  differential diagnostics solves based on the results of the  hormonal tests performed is to determine the main cause of anovulatory disorders. [13]

Treatment anovulatory cycle

Taking into account the cause of the anovulatory cycle, its treatment is also carried out.

Medications are often prescribed to induce ovulation, including drugs from the estrogen antagonist group Clomiphene (Clomid, Clostilbegit) or Tamoxifen (Nolvadex), and the aromatase enzyme inhibitor Letrozole (Femara).

With dysfunction of the hypothalamic-pituitary system, it promotes the development of follicles and stimulates ovulation Follitropin alfa (by injection) - 75-150 IU once a day (during the first seven days of the cycle). This drug is contraindicated for cysts and ovarian hypertrophy, tumors of the hypothalamus, pituitary, uterus or mammary glands. Its side effects are nausea, vomiting, abdominal and joint pain, ascites and the formation of venous blood clots. [14]

Also, the FSH deficiency can be replenished by the injectable Puregon (Follitropin beta).

Progesterone analogs Dydrogesterone (Dyufaston) and Utrozhestan with anovulatory cycle with a deficiency of this hormone are used to stimulate the synthesis of pituitary gonadotropins (LH and FSH) and the luteal phase. The dosage is determined by the doctor, for example, the daily dose of Utrozhestan is 200-400 mg, it is taken for 10 days (from 17 to 26 days of the cycle). This drug is contraindicated in deep vein thrombosis, liver failure, breast cancer. Side effects include headache, sleep disturbances, fever, nocturnal hypergilrosis, breast tenderness, vomiting, and bowel disorders. [15],  [16],  [17], [18]

In the case of hyperprolactinemia, Bromocriptine (Parlodel) is used to reduce the production of prolactin by the pituitary gland. If the anovulatory cycle is associated with increased production of male hormones by the adrenal glands, corticosteroids are prescribed. [19]

Herbal therapy or herbal medicine to maintain ovulation is most often aimed at restoring hormonal balance. For this purpose, on the recommendation of a doctor, grass and seeds of creeping tribulus can be used; grass and flowers of red clover; Dioscorea (wild yam) root; the root and rhizomes of cimicifuga (Voronets racemose); linseed oil and oil from evening primrose seeds (primrose or evening primrose). Particularly noteworthy are the seeds, fruits and leaves of a tree-like shrub of the family of the lamellar - common prutnyak (another name is sacred vitex). Extracts from these parts of the cane increase the activity of dopamine in the brain, which leads to a decrease in prolactin release, as well as normalization of the balance of progesterone and estrogen and an increase in LH levels.

Also read the article -  Treatment of anovulation

Prevention

You can prevent the anovulatory cycle in case of weight problems: if the body mass index rises, you need to lose excess; with significant weight loss - gain the missing kilograms. [20]

For women's health, you need to adhere to a healthy lifestyle and eat well. See -  Products to restore hormonal levels

Forecast

Considering that it is possible to restore ovulation with the help of appropriate drugs, the  [21] prognosis of the anovulatory cycle is considered favorable in almost 90% of cases.