Obstetrics and Gynecology - A. M. Gromova 2000

Menstrual Function Disorders
Forms of Menstrual Cycle Disorders
Amenorrhea

Amenorrhea is the absence of menstruation for 6 months or longer. This condition is not an independent disease, but rather a syndrome reflecting various local and systemic changes in a woman's body arising from multiple causes, which ultimately result in prolonged reproductive and menstrual dysfunction.

Physiological amenorrhea is distinguished—the absence of menstruation during Pregnancy and breastfeeding, in childhood, during menopause and postmenopause (persistent absence of menstruation in advanced age), as well as pathological amenorrhea caused by underlying disorders in a woman's body. Amenorrhea can be primary (menstruation has never occurred) or secondary (menstruation was previously established but has ceased). A distinction is also made between true amenorrhea (the bodily processes necessary for menstruation are absent) and false (cryptomenorrhea, where endometrial desquamation occurs in the Uterus, but menstrual Blood cannot escape due to anatomical obstructions, such as an imperforate hymen or vaginal atresia).

Depending on the level of the regulatory system responsible for the Menstrual cycle, amenorrhea is classified into cortical, hypothalamic, pituitary, ovarian, and uterine forms, as well as amenorrhea associated with adrenal and thyroid disorders.

Cortical amenorrhea occurs in cases of severe stress, starvation (such as amenorrhea during wartime), an intense desire to conceive or, conversely, a fear of pregnancy (pseudocyesis), Schizophrenia, meningoencephalitis, and similar conditions. In any case, the etiological factor induces a focus of constant impulse generation in the Cerebral Cortex, disrupting the normal relationship between the cortex and subcortical structures of the Brain, leading to the subsequent release of corticotropic Hormones into the bloodstream. In high concentrations, these hormones can block the hypothalamic synthesis of releasing factors and consequently limit the secretion of Pituitary Hormones, resulting in a lack of cyclic Changes in the Ovaries and uterus.

A certain role in the onset of stress-induced amenorrhea is played by elevated endorphin levels, which are also capable of inhibiting luteotropin synthesis.

Depending on the period of a woman's life when the negative etiological factor acts, cortical amenorrhea can be either primary or secondary. Primary cortical amenorrhea develops during Puberty and is accompanied by underdevelopment of the uterus and secondary sexual characteristics.

Hypothalamic amenorrhea develops due to damage to the diencephalic region resulting from neuroinfections, intoxications, or psychological trauma. Several forms of hypothalamic amenorrhea are distinguished.

Amenorrhea caused by Adiposogenital Dystrophy (Babinski-Fröhlich syndrome) develops in childhood in connection with tumor, traumatic, or infectious damage to the Hypothalamus. The clinical picture is characterized by hypothalamic obesity with predominant fat deposition on the face, abdomen, and Mammary Glands, growth retardation, possible increased intracranial pressure or headaches in cases of a tumor origin, genital hypoplasia, and underdevelopment of secondary sexual characteristics.

Amenorrhea in Laurence-Moon-Biedl syndrome arises from multiple Gene defects inherited in an autosomal recessive manner, leading to damage of the hypothalamic nuclei. The clinical picture resembles that of adiposogenital dystrophy; however, unlike the latter, patients exhibit severe mental retardation and Congenital Malformations (visual impairment, deafness, polydactyly, Syndactyly, Skull anomalies, or other defects), while excessive adipose tissue accumulation is observed from the first days of life.

Amenorrhea in Morgagni-Stewart-Morel syndrome is also a congenital pathology (inherited in an autosomal dominant manner), but its clinical manifestations begin to develop after the age of 35–40. It is characterized by a triad of symptoms: congenital frontal hyperostosis resulting in narrowing of the sella turcica Diaphragm with subsequent damage to the hypothalamo-pituitary region; adiposogenital-type obesity; and hypertrichosis with normal urinary levels of 17-KS and 17-OHCS in the female patient. Headaches, convulsive seizures, and mental state alterations are possible.

The galactorrhea-amenorrhea syndrome includes the Chiari-Frommel syndrome (arising as a complication of the postpartum and post-abortion periods) as well as the syndromes described by Castillo, Forbes, and Albright, in which galactorrhea and amenorrhea occur in nulliparous women due to psychological trauma, tumor development, or medication use. The Pathogenesis and Clinical Features of these conditions are similar. The clinical picture presents a triad of symptoms: amenorrhea, galactorrhea, and Atrophy of the external and later internal genitalia combined with breast hypertrophy. It is caused by a dysfunction of hypothalamic centers responsible for regulating prolactin production in the Pituitary Gland. Prolonged hyperprolactinemia suppresses FSH synthesis and blocks its action on the ovaries.

The cause of pituitary amenorrhea is predominantly damage to the pituitary gland by tumor or inflammatory processes, or by cerebral Circulation disorders (vascular thrombosis, necrosis).

As a result, functional failure of the pituitary gland occurs regarding the synthesis of all hormones (panhypopituitarism), gonadotropins alone (hypogonadotropism), or hormonal dyscorrelation (hypogonadotropism combined with Growth Hormone and ACTH hyperproduction).

Congenital panhypopituitarism causes amenorrhea in Pituitary dwarfism. The main signs of this condition are growth retardation noticeable from 3–5 years of age with proportional Skeletal Structure, absence of secondary sexual characteristics, and underdevelopment of the reproductive Organs.

Acquired deficiency of all pituitary hormones characterizes Sheehan's syndrome, which results from pituitary Hemorrhage or necrosis following complicated labor or septic abortion. Following delivery, headaches appear, agalactia occurs, and the patient's body weight decreases. Subsequently, symptoms of peripheral endocrine gland deficiency appear (amenorrhea, Myxedema), secondary hypoplasia of the Reproductive System, breast atrophy, and regression of secondary sexual characteristics. Patients are emaciated, anemic, and prone to hypopituitary coma due to acute adrenal cortex insufficiency.

Simmonds' disease presents a similar clinical picture, in which panhypopituitarism is caused by total pituitary damage from tumors, tuberculosis, Syphilis, or abscesses.

When There is a deficiency solely in gonadotropin production while the secretion of other pituitary hormones is preserved, pituitary eunuchoidism develops. The condition manifests by the end of puberty and is characterized by amenorrhea and underdevelopment of the external genitalia and breasts with normal growth rates.

When pituitary hormone synthesis is unbalanced—where suppressed gonadotropin synthesis is combined with elevated growth hormone production—gigantism or acromegaly develops. The former pathology is caused by pituitary damage before puberty and is characterized by tall stature (over 190 cm) with normal body proportions.

Acromegaly develops after growth has ceased, typically in middle or older age. The fingers and toes progressively enlarge, the menstrual cycle becomes disturbed, and subsequently the BONES OF THE skull (lower jaw, supraorbital ridges, Nose, ears) enlarge.

Cushing's Disease arises from corticotropin hyperproduction and adrenal cortex hyperplasia associated with a basophilic Adenoma of the pituitary, encephalitis, or HEAD trauma.

Clinical signs include pituitary-type obesity (fat deposition in the upper body and face), Menstrual disorders IN the form of amenorrhea or hypomenstrual syndrome, increased Hair growth on the face, trunk, and extremities, and acne vulgaris. Subsequently, arterial Hypertension develops, leading to cardiosclerosis, nephrosclerosis, or retinal changes. Bone demineralization with The Development of Osteoporosis is also noted.

Gynecological examination reveals hyperpigmentation of the external genitalia. The uterus is hypotrophic. The ovaries frequently undergo cystic degeneration. Cyclic changes in the mucous membrane of the uterus and Vagina cease and remain prolonged at the proliferative stage.

The Diagnosis is confirmed by determining The excretion of 17-KS and 17-OHCS and by performing hormonal dynamic tests with prednisolone and dexamethasone. Cushing's disease is characterized by a significant increase in 17-OHCS excretion with normal or slightly elevated urinary 17-KS levels, as well as positive results from the hormonal tests.

Amenorrhea also occurs in empty sella syndrome, which develops as a result of pituitary surgery or necrosis and is characterized by decreased secretion of all tropic pituitary hormones.

Ovarian amenorrhea develops in the event of complete failure of ovarian hormonal function combined with relatively preserved pituitary function. It most commonly occurs due to primary ovarian damage resulting from chromosomal abnormalities.

Turner syndrome develops prenatally in the absence of one X chromosome and is manifested by ovarian dysgenesis, underdevelopment of the reproductive organs, and somatic anomalies, such as short stature, webbed neck with lateral folds, and bone and internal organ malformations. Hormonal studies reveal a significant increase in gonadotropin levels accompanied by a decreased estrogen concentration. 17-KS and 17-OHS secretion remains within the normal range. Sex Chromatin is negative in such patients.

Both pure and mixed forms of ovarian dysgenesis are distinguished. The pure form is characterized by the underdevelopment of the reproductive system without somatic anomalies. The mixed form is extremely rare and presents with an ambiguous phenotype and intersex STRUCTURE OF THE external and internal genitalia.

Triple X syndrome is distinguished by the presence of three X Chromosomes with a 47,XXX karyotype and is characterized by primary amenorrhea and Infertility.

Testicular feminization syndrome (Morris syndrome) is a form of male pseudohermaphroditism. It is characterized by the manifestation of a female phenotype in genetically male individuals with a 46,XY karyotype due to congenital androgen insensitivity. The most critical diagnostic features of this syndrome are negative sex chromatin and the absence of a uterus in an individual with a female phenotype.

Hypohormonal amenorrhea can also develop during puberty or the reproductive years as a result of ovarian Damage caused by radiation, intoxication, severe inflammatory processes, and extragenital diseases. When the etiologic factor exerts its effect before puberty is complete, alongside pronounced infantilism with primary amenorrhea, somatic development is disrupted in a eunuchoid pattern (rapid, disproportionate growth with longitudinal body dimensions predominating, and excessive fat deposition in the thighs). During the reproductive years, chronic inflammatory processes frequently cause hypohormonal amenorrhea due to the persistent presence of infectious agents in the body, to which ovarian tissue is exceptionally sensitive. These processes lead to the premature decline of follicular apparatus function, as well as atrophy of the uterus and endometrium. Ovarian hypofunction is frequently combined with hypothalamic-pituitary disorders resembling menopausal symptoms.

Occasionally, a hyperhormonal form of ovarian amenorrhea is encountered, caused by follicular persistence without endometrial desquamation. Such amenorrhea is invariably secondary, appearing after a period of normal menstruation. Functional diagnostic tests indicate a state of heightened estrogen saturation in the body. Histological examination of an endometrial biopsy specimen reveals glandular-cystic endometrial hyperplasia.

Stein-Leventhal syndrome is characterized by impaired ovarian steroidogenesis, leading to androgen overproduction and suppressed estrogen synthesis. In this condition, the ovaries become scleropolycystic—that is, enlarged with a thickened tunica albuginea; the ovarian tissue contains numerous cystic follicles, accompanied by excessive Connective Tissue proliferation and vascular sclerosis. Clinically, this manifests as amenorrhea or hypomenstrual syndrome, obesity, infertility, and hirsutism, with hair growth in typical male distribution areas, such as the face (in the form of sideburns or a mustache), along the linea alba, and around the areolae.

The disorder typically begins several years after menarche, with symptoms progressing gradually. Detailed evaluation reveals an absence of estrogenic influence, and basal body Temperature remains monophasic. Endometrial biopsy demonstrates proliferation without pronounced hyperplasia, whereas in long-standing cases, the endometrium appears atrophic. Determining the level of 17-KS holds the highest diagnostic value (showing a mild elevation), especially when combined with hormonal tests whose outcomes confirm the ovarian Water/144.html">Origin of the hyperandrogenism.

Uterine amenorrhea is the absence of menstruation resulting from endometrial damage caused by tuberculosis, Gonorrhea, excessive Curettage of the uterine lining during abortion, post-intrauterine iodine administration, the development of intrauterine synechiae, and other pathological processes. Gynecological examination reveals no apparent changes in the genitalia. Ovarian function remains unimpaired for a prolonged period, though secondary pituitary-adrenal insufficiency eventually develops.

Hormonally, despite the presence of amenorrhea, biphasic yet "silent" (concealed) menstrual cycles are diagnosed. Progesterone and estrogen-progestin tests yield negative results, confirming the inability of the damaged endometrium to respond to normal hormonal stimulation.

Amenorrhea associated with adrenal cortex disorders (adrenogenital syndrome) arises from cortical hyperplasia or tumor formation. Three Clinical forms of this disorder are distinguished: congenital, pubertal, and postpubertal.

Congenital adrenogenital syndrome is caused by 21-hydroxylase deficiency, leading to reduced cortisol synthesis and a compensatory increase in ACTH production. The latter drives both a compensatory rise in cortisol production and heightened androgen output, which together shape the Clinical presentation of the disease.

Congenital adrenogenital syndrome manifests as female pseudohermaphroditism. The ovaries and uterus develop normally, and the karyotype is 46,XX. During their first decade of life, girls with the congenital form of adrenogenital syndrome exhibit signs of precocious heterosexual puberty. The most informative diagnostic test is an elevated level of urinary 17-KS and/or blood testosterone, 17-OHP, and DHEA, which normalize following a glucocorticoid suppression test.

The pubertal form of adrenogenital syndrome manifests as early puberty, a male body habitus, and signs of virilization (excessive hair growth, clitoromegaly, voice deepening, and acne).

The postpubertal form is characterized by delayed menarche (at 14–16 years of age), a family history of hypertrichosis and early pregnancy loss among maternal or paternal relatives, persistent hypertrichosis and irregular menses starting from menarche, virile features, elevated urinary 17-KS levels alongside increased blood testosterone, DHEA, and 17-OHP, which decline to normal ranges following dexamethasone administration.

Amenorrhea associated with thyroid disorders (hypothyroidism, thyrotoxicosis) develops gradually and is frequently accompanied by infertility and miscarriages. Reproductive disorders begin as a hypomenstrual syndrome, which transitions into amenorrhea as the underlying disease progresses. No external structural changes in the reproductive system are observed in this form of amenorrhea.

The primary objective in evaluating patients with amenorrhea is to determine its underlying cause. The patient must undergo thorough examination by related specialists, particularly a neurologist, internist, ophthalmologist, otolaryngologist, endocrinologist, and geneticist. Sex chromatin and karyotype analyses are performed according to indications. If Central Nervous system pathology is suspected, skull radiography—particularly of the sella turcica—is conducted.

To assess The Nature of ovarian hormonal function, evaluations of gonadotropins, Sex Hormones, 17-KS, and 17-OHS are employed, along with functional diagnostic tests (basal body temperature measurement, evaluation of the "pupil" sign, cervical mucus crystallization, mucus spinnbarkeit, and hormonal colpocytological studies), alongside histological examination of endometrial biopsy specimens. Various hormonal tests are performed as indicated to pinpoint the level of the lesion within the cycle-regulating system.

Treatment for amenorrhea must target the elimination of its underlying cause. Across all forms of amenorrhea, primary emphasis is placed on a rational daily schedule, adequate rest, proper Nutrition, and general strengthening therapy. When inflammatory processes are the cause, anti-inflammatory agents are administered. Tumors require surgical intervention, whereas Brain Tumors are managed with radiotherapy combined with the administration of gonadotropins, sex hormones, and thyroid preparations.

For amenorrhea of central origin, synthetic liberins, statins, follicle-stimulating and luteinizing hormones, or human chorionic gonadotropin, humegon, puregon, pregnin, duphaston, clomiphene, and clostilbegyt are prescribed to stimulate ovulation.

In cases of Hypogenitalism, treatment courses are administered starting with gonadotropins (human chorionic gonadotropin or profasi at 500–1500 IU every 2–3 days for 1 month), followed by sex hormones: folliculin at 5000–10000 IU or microfolliculin at 0.01 mg twice daily for 20 days with 10-day intervals. Upon the appearance of a withdrawal bleeding response, a 2.5% progesterone solution (1 ml) is administered intramuscularly for 7–8 days during the second phase of the menstrual cycle. The treatment course spans 2–3 months, with an average overall treatment duration of 2 years.

Therapy utilizing preparations containing FSH and LH (pergonal or pergogrin at 1 ml [750 IU] for 7–12 days) is employed, followed by The stimulation of ovulation and corpus luteum formation using human chorionic gonadotropin: profasi at 1000 IU on day 14 of treatment or choriogonin at 3000 IU on days 12, 14, and 16. The administration of the LH-releasing hormone agonist buserelin at a dose of 500 mcg/day is also a viable option.

In cases of hyperprolactinemic amenorrhea (amenorrhea-galactorrhea syndrome), following necessary diagnostic evaluations to rule out a pituitary adenoma, patients undergo treatment to suppress mammary gland secretion via the administration of parlodel (bromocriptine). Treatment is initiated at 1/4 to 1/2 of a tablet (with 1 tablet containing 2.5 mg), increasing the dose by 1/2 tablet every 2–3 days until a daily dose of 2.5–5 mg is reached. The treatment course should last 28–30 days and must be conducted under continuous monitoring of its efficacy through basal body temperature measurements and colpocytological evaluations. If ovulation is absent and the duration of the second cycle phase remains unchanged after the initial treatment course, the dose is increased by 2.5 mg per day with each successive course. The total duration of treatment is 6–8 months.

In pituitary dwarfism, one of the primary therapeutic interventions is height correction using somatotropin, THYROID HORMONES, and glucocorticoids. Sex hormones are prescribed for virilization, while gonadotropic and sex hormones are used for sexual infantilism. Treatment of panhypopituitarism (Simmonds' disease and Sheehan's syndrome) is carried out via hormone replacement therapy addressing the deficient hormones—corticosteroids, androgens, estrogens, and thyroidin—while accounting for their mutual interactions.

Treatment for ovarian amenorrhea should aim to enhance bodily feminization. During puberty, in cases of growth retardation, thyroid preparations and anabolic Steroids (nerobol, retabolil) are prescribed. Sex hormones, particularly estrogens, should only be administered after 18 years of age due to their potential to induce premature epiphyseal fusion in younger individuals.

If necessary, therapy is initiated with small doses of estrogens: microfolin at 0.05-0.1 mg daily. During the first 8-12 months of treatment, they are administered for 20 days followed by 10-day breaks. Afterward, patients are switched to cyclic estrogen-progesterone therapy with a gradual dosage reduction of 25-50%. Cyclic therapy is carried out for 1.5-2 years in courses lasting 2-3 months with monthly intervals.

For long-term therapy, sustained-action drugs have recently been recommended: dimestrol 0.6%-2 ml intramuscularly, or sterile estradiol or diethylstilbestrol pellets implanted into the subcutaneous adipose tissue, which exert their effect for 40-80 days.

Ovarian function is improved by prescribing 5% copper sulfate iontophoresis to the lower abdomen in The first phase, and 1-2% zinc sulfate iontophoresis In the second phase. Estrogens are recommended to be combined with ascorbic acid, and progesterone with Folic acid or tocopherol acetate.

For Stein-Leventhal syndrome, resorption-promoting ovulation-stimulating therapy, ovarian puncture during laparoscopy, or wedge resection of the ovaries is used. If hormone replacement therapy is necessary, it is administered according to Kvater's scheme: 1 ml of 0.1% folliculin solution is injected intramuscularly daily for 12 days, followed by 1 ml of 0.1% folliculin solution and 0.5 ml of 1% progesterone solution for 4 days, and then 1 ml of 1% progesterone solution intramuscularly for 8 days.

In testicular feminization, removal of the Testes, clitoral reduction, vaginoplasty, and estrogen therapy to stimulate breast development are recommended.

Treatment for uterine amenorrhea must be etiological. In the presence of intrauterine synechiae, curettage of the uterine cavity is performed, followed by estrogen therapy and the insertion of an intrauterine device for 2-3 months. Prior to surgery, it is advisable to introduce lidase (64 IU) into the uterine cavity or administer ultrasound therapy targeting the projection area of the uterus. Endometrial transplantation into the uterus is also possible. In cases of total obliteration, treatment often proves ineffective.

In the treatment of adrenogenital syndrome, glucocorticoids are used to compensate for cortisol deficiency and suppress excessive corticotropin synthesis. Dexamethasone is prescribed at 0.25-0.125 mg (1/2-1/4 tablet) daily over an extended period, monitored by basal body temperature measurements, colpocytological examinations, and monthly 17-KS assays (levels should be maintained at the lower limit of normal). Such treatment should increase the body's estrogen saturation, restore ovulation, and prolong the second phase of the cycle. To enhance feminization, glucocorticoid therapy is supplemented with estrogens (the optimal ratio is 50:1). If necessary, plastic surgery (clitoral reduction) or surgical intervention for an adrenocortical tumor is performed.

When amenorrhea develops as a result of thyroid disorders, appropriate corrective therapy with thyroid hormone medications or antithyroid agents is administered depending on the specific form of the condition. Often, following the Treatment of the underlying disease, the menstrual cycle in such patients is restored quite rapidly.