Stromal tecomatosis is a benign hormone—active hyperplasia of the ovarian stroma, accompanied by increased androgen synthesis and increased peripheral estrogen production. It is manifested by signs of virilization (hirsutism, coarsening of the voice, hypertrophy of the clitoris), oligomenorrhea, amenorrhea, infertility, visceral obesity. For diagnosis, the content of androgens, estrogens, LH, FSH is examined, pelvic ultrasound, CT, ovarian MRI, diagnostic laparoscopy with histological analysis of the biopsy is performed. Treatment is combined with resection or bilateral removal of the ovaries and the appointment of hormonal drugs.
Stromal tecomatosis (ovarian hyperthecosis, stromal ovarian hyperplasia, Frenkel syndrome) is a rare gynecological disease, usually diagnosed in perimenopause or postmenopause. Pathological overgrowth of the ovarian stroma is also detected by histological examination of the material in 0.45% of young patients who underwent ovarian surgery. Although the causes of tecomatosis remain unknown, the risk of developing stromal hyperplasia increases with an unfavorable premorbid background (extragenital somatic, endocrine pathology) and impaired formation of the menstrual cycle (67.8% of sick women had early or late menarche). The urgency of timely diagnosis of hyperthecosis is due to the high probability of the development of associated estrogen-sensitive tumors and primary infertility, which is detected in 65% of patients of reproductive age.
The etiology of Frenkel syndrome has not been established to date. Presumably, the transformation of interstitial ovarian cells into epithelioid teca-cell elements with the subsequent formation of foci of tecomatosis is due to a failure of hormonal regulation in women predisposed to the disease. Specialists in the field of gynecology and endocrinology offer two main theories of the occurrence of stromal ovarian hyperplasia:
- Hereditary predisposition. In some cases, ovarian hyperthecosis is detected in close relatives, which may indicate its connection with an X-chromosome defect. Also, genetic abnormalities that cause increased activity of enzymes that are responsible for the conversion of cholesterol into steroids, including androgens, and 5α-reductase, which transforms testosterone into its bound form (dihydrotestosterone), are not excluded.
- Hypothalamic-pituitary disorders. According to a number of authors, stromal tecomatosis occurs due to hyperstimulation of the ovarian stroma by gonadotropins, primarily luteinizing hormones, and the disorder is associated with a violation of the regulation of the menstrual cycle in perimenopause. However, the level of LH and FSH in hyperthecosis is not always increased. The influence of tumor products of protein catabolism is considered as an additional factor.
The key link in the development of pathological disorders in stromal hyperthecosis is the hormonal activity of hyperplastic epithelioid techa cells secreting sex steroid hormones. The ovarian capsule and “dormant” primordial follicles are not involved in the process. Tecomatous foci are not separated from normal tissue, do not grow infiltratively and do not disintegrate. Secretory activity of teca cells leads to an increase in the level of androgens, under the influence of which the virilization of the body occurs, and relative hyperestrogenism due to peripheral conversion of androstenedione to estrone in adipose tissue. Simultaneously with the increase in estrogen production, sensitivity to hormonal stimulation of functional tissues in target organs increases, which is manifested by appropriate symptoms.
When systematizing clinical forms of stromal tecomatosis, the degree of involvement in the pathological process of ovarian tissue and the distribution of secreting teca cells are taken into account. The variant of hyperthecosis is taken into account when predicting the course of the disease and choosing the optimal treatment regimen. There are the following forms of stromal hyperplasia:
- Focal. It is considered the easiest variant of the disease. Pathological changes are localized in part of the organ. The shape of the ovary is changed unevenly.
- Diffuse. The most common form of hyperthecosis. The cortical layer of the ovaries is thickened evenly, partial involvement of brain matter in the process is possible.
- Nodal. Teka cells are united in nodular clusters that are not separated by a capsule from healthy ovarian tissue. Individual foci of tecomatosis merge with each other.
The most notable clinical manifestation of Frenkel syndrome is virilization caused by hyperandrogenism. Women complain about the appearance of persistent, slowly progressing acne. There are signs of hirsutism — excessive male-type hair growth with hair growth above the upper lip, on the chin, cheeks, in the areolar region, along the white line of the abdomen, on the limbs, back, inner thighs. In patients with stromal hyperplasia, the clitoris increases, the timbre of the voice decreases, male-type baldness is possible. As a rule, such women resemble men in physique — they have a narrow pelvis, wide shoulders, small breasts. Visceral obesity often develops with an increase in the volume of the abdomen, striae and black acanthosis may appear on the skin — hyperpigmentation of symmetrical skin folds.
Against the background of an increased content of androgens in the reproductive age, menstrual and childbearing function are disrupted. The time of menstruation shortens, intermenstrual intervals lengthen, spotting becomes scarce. As the disease progresses, secondary amenorrhea may develop with the complete cessation of menstruation. Usually, women with stromal ovarian hyperplasia cannot get pregnant and carry a child. Relative hyperestrogenism in ovarian tecomatosis is more noticeable during menopause, postmenopause and is manifested by the so—called signs of “rejuvenation” – the appearance of bloody vaginal discharge, swelling of the mammary glands, low severity or absence of involutive changes in the mucous membranes of the reproductive organs.
The hormonal imbalance that occurs with stromal tecomatosis leads to the development of a number of serious somatic diseases. Almost all patients have insulin-independent diabetes mellitus with high insulin resistance, obesity of II-III degree. The risk of arterial hypertension, autoimmune thyroiditis, diffuse toxic and proliferating colloidal goiter, hypothyroidism, intracellar pituitary adenoma increases. Against the background of increased estrogen levels, recurrent uterine bleeding occurs, associated fibrocystic mastopathy and endometrial cancer develop more often.
Diagnostic search for suspected stromal tecomatosis is aimed at identifying signs of secretory activity of techa cells and characteristic morphological changes in ovarian tissue. Examination and classical physical examinations suggest the presence of hyperthecosis, however, data from laboratory and instrumental studies are required to verify the diagnosis. The survey plan usually includes:
- Examination on the chair. During bimanual palpation, enlarged painless appendages of a tight elastic consistency are determined. When examined in mirrors, menopausal and postmenopausal patients have little or no characteristic signs of age-related involution of the vaginal mucosa and exocervix.
- Laboratory tests. A diagnostically significant criterion is an increase in the total testosterone content in the blood serum of more than 5.2 nmol/l. Usually, the concentration of estradiol and LH is increased (at normal FSH levels). The content of DEA-sulfate in the blood is within the normal range, the level of 17-CS may increase.
- Transvaginal ultrasound of the pelvic organs. Both ovaries are usually enlarged in size, have an oval or round shape. Their tissue is compacted, stroma hyperplasia is pronounced. In premenopause, the follicles are usually shifted to the periphery of the organ, single cystic changes may occur.
- CT and MRI of the ovaries. A bilateral increase in the volume of the ovaries by 3-8 times is determined, while the ovarian stroma looks homogeneous. Tomographic examination allows you to accurately assess the structure of the organ and differentiate tecomatosis from possible volumetric neoplasms.
- Diagnostic laparoscopy. During an endoscopic examination, a biopsy can be obtained for histological analysis. Detection of luteinized stroma cells with lipophilic light cytoplasm in the material is one of the most reliable signs of the disease.
As additional methods, determination of the insulin resistance index (HOMA-IR), assessment of thyroid hormone levels, hysteroscopy with biopsy or separate diagnostic curettage to detect hyperplastic processes in the endometrium, ultrasound of the mammary glands, mammography are recommended. The disease is differentiated with Itsenko-Cushing syndrome, adrenogenital syndrome, polycystic ovaries, tecoma, ovarian androblastoma, pituitary tumors. If necessary, an endocrinologist, oncologist, neuropathologist, and neurosurgeon are involved in the examination of the patient.
Treatment of stromal tecomatosis
When choosing therapeutic tactics for hyperthecosis, the patient’s age, her reproductive plans, and the severity of hyperplasia in estrogen-sensitive target organs are taken into account. The most effective combination treatment combining a surgical approach with pathogenetic and symptomatic drug therapy. The main goal is to eliminate excess testosterone secretion. The optimal treatment options are:
- In the absence of reproductive plans: during perimenopause and postmenopause, bilateral ovariectomy is usually performed. As an alternative, patients with contraindications to surgical treatment and with refusal to remove the ovaries may be offered long-term administration of gonadotropin releasing factor agonists. The therapeutic effect of GnRH agonists is usually achieved no earlier than 6 months after the start of use.
- If there are plans for childbirth: the treatment regimen is similar to the treatment of polycystic ovaries and includes oral contraceptives, antiandrogenic drugs, GnRH agonists, which allow to restore the sensitivity of ovarian tissue to gonadotropins and stimulate ovulation. To reduce the signs of hirsutism, various epilation techniques are used. In some cases, wedge-shaped ovarian resection is effective.
An important condition for improving the effectiveness of treatment of stromal tecomatosis is weight correction and the use of drugs that reduce the resistance of cells to glucose. This reduces the risk of hyperplasia and neoplasia of the endometrium, myometrium, and alveolar tissue of the mammary glands. According to observations, the additional appointment of nasal electrophoresis of vitamins B1, B6 contributes to the improvement of the condition of patients.
Prognosis and prevention
Although teka cells do not malignate, and ovarian tecomatosis is not a life-threatening disease, it significantly worsens the patient’s quality of life and increases the likelihood of developing malignant tumors of the uterus and mammary glands. Radical surgical treatment allows you to completely get rid of the clinical signs of the disease. Organ-preserving operations in combination with hormone therapy provide a decrease in androgen levels, getting rid of signs of virilization, but only a small number of patients manage to restore reproductive function. Primary prevention measures have not been developed. The purpose of secondary prevention is early detection of the disease during a routine examination by a gynecologist and ultrasound screening. Tertiary prevention involves timely adequate treatment that minimizes the likelihood of complications (recurrent uterine bleeding in postmenopause, neoplasms of the breast and reproductive organs).