Hormone therapy: gestrinone
An ethinyl testosterone derivative, gestrinone has a complex pharmacological profile. It exhibits pronounced antiestrogenic and antiprogestogenic effects (by binding to the corresponding receptors) along with a mild androgenic effect. The latter is due to a decrease in sex hormone-binding globulin levels, leading to an increased concentration of free testosterone in the blood.
The drug's mechanism of action is based on the suppression of gonadotropin secretion—luteinizing hormone (LH) and follicle-stimulating hormone (FSH). During administration, estradiol and progesterone levels drop by 50–70%, which naturally induces endometrial atrophy and the development of drug-induced amenorrhea.
The clinical picture during therapy demonstrates high efficacy: symptoms are resolved in 75–95% of patients within 4 months of use. However, 30–45% of women develop adverse reactions: weight gain, acne, seborrhea, hirsutism, deepening of the voice, depressive episodes, hot flashes, and dyslipidemia (decreased high-density lipoprotein levels and increased low-density lipoprotein levels).
Use of mifepristone and emerging methods
Mifepristone is a synthetic steroid acting as a potent progesterone inhibitor. It demonstrates pronounced antiprogestogenic and antiglucocorticoid activity. An important feature is its direct antiangiogenic effect: the drug sharply reduces the content of vascular endothelial growth factor (VEGF) and the expression of its RNA molecule in endometrial tissues.
In the treatment of endometriosis, the doses and duration of mifepristone administration are still undergoing clinical evaluation. It is known that long-term use of high doses is associated with the risk of endometrial hyperplasia, as the protective antiproliferative effect of progesterone is completely eliminated.
Promising paths of pathogenetic therapy that have not yet gained widespread clinical use include the administration of aromatase inhibitors, prostaglandin synthesis inhibitors, and angiogenesis inducers.
Symptomatic and surgical treatment
Symptomatic treatment is carried out strictly in parallel with pathogenetic treatment to alleviate the inflammatory process and relieve pelvic pain. The physician's arsenal includes:
- Nonsteroidal anti-inflammatory drugs (NSAIDs): indometacin, ketoprofen, naproxen, celecoxib.
- Antispasmodics and analgesics.
- Iron supplements: prescribed upon the development of posthemorrhagic anemia against the background of heavy bleeding.
Overall treatment success directly depends on properly selected hormonal support and timely surgical intervention. The main rule of surgical treatment is strict prevention of implantation dissemination of cells. The surgeon must avoid any contact of affected tissues (endometriotic heterotopias) and the endometrium with the peritoneum or the edges of the surgical wound. During the laparoscopic approach, the removal of the uterus (in adenomyosis) or ovarian endometriotic lesions through the operating channel must be performed exclusively in a special containment bag.
Prognosis and prevention of recurrence
Endometriosis and adenomyosis are classified as recurrent diseases. Disease recurrence statistics are quite high:
- Within up to 5 years after treatment, relapses occur in 40% of patients.
- At periods exceeding 5 years, the recurrence rate rises to 74%.
To prevent the return of pathology after conservative surgeries, it is advisable to prescribe long-term hormone therapy. In young women during the postoperative period, the use of hormonal contraception serves as an effective method to curb the disease.
A favorable prognostic factor is the administration of hormone treatment in premenopausal patients, as the subsequent onset of physiological postmenopause naturally prevents disease recurrence. Complete absence of recurrence is guaranteed only by radical surgeries for endometriosis.
Briefly: answers to topical questions
Which groups of pharmacological drugs are used for the conservative treatment of adenomyosis?
Hormonal drugs, pathogenetic therapy agents, and symptomatic therapy are used for the conservative treatment of adenomyosis.
- Ethinyl testosterone derivatives — gestrinone.
- Progesterone inhibitors — mifepristone; currently undergoing dose and treatment duration evaluation.
- Nonsteroidal anti-inflammatory drugs — indometacin, ketoprofen, naproxen, celecoxib, etc., for pain and inflammation relief.
- Antispasmodics and analgesics — for symptomatic therapy.
- Iron supplements — prescribed for posthemorrhagic anemia.
- Aromatase inhibitors, prostaglandin synthesis inhibitors, angiogenesis inducers — promising directions of pathogenetic therapy that have not yet gained widespread use.
What instrumental diagnostic methods are used to confirm adenomyosis?
Visualization and endoscopic instrumental diagnostic methods are used to confirm adenomyosis.
- Ultrasound examination — transvaginal ultrasound is the method of choice for assessing structural changes.
- Hydrosongraphy — increases the diagnostic informativeness of early forms of the disease.
- Magnetic resonance imaging — a highly informative method for detailed assessment of myometrial structure.
- Hysteroscopy — an endoscopic method with an accuracy of up to 92%, allowing the assessment of the contour of the walls.
- Hysterosalpingography — used to diagnose the nodular form by identifying specific "out-of-contour shadows".
What are the indications for radical surgical treatment (hysterectomy) in adenomyosis?
Radical surgical treatment for adenomyosis is performed in the following cases.
- Inefficacy of hormone therapy — hysterectomy without adnexa is indicated in the absence of an effect from hormonal treatment.
- Contraindications to hormone therapy — hysterectomy without adnexa is indicated when hormone therapy cannot be administered.
- Nodular form of adenomyosis with abnormal uterine bleeding — surgical treatment is recommended; the radical method is total hysterectomy.
- Stage 3–4 adenomyosis — the pregnancy rate is low, 10–15%; total hysterectomy is indicated as the only effective radical method.
What are the clinical and morphological forms of adenomyosis?
Four main clinical and morphological forms of adenomyosis are distinguished depending on the nature of myometrial involvement.
- Diffuse form — characterized by uniform involvement of the myometrium.
- Focal form — manifests as isolated foci within the thickness of the uterine wall.
- Nodular form — represented by the formation of nodes that resemble myoma but differ by the absence of a capsule.
- Cystic form — characterized by the presence of cystic cavities with contents.
To memorize the side effects of gestrinone, use the association with the "male type": due to its mild androgenic effect (increased free testosterone), patients develop acne, seborrhea, hirsutism, voice deepening, and weight gain.
Class and exam questions
How to properly extract tissues during laparoscopic surgery for adenomyosis?
The removal of affected tissues (including the uterus) through the operating channel must be performed strictly in a special containment bag. This is necessary to prevent the implantation dissemination of endometrial cells onto the peritoneum and the surgical wound.
What is the probability of disease recurrence after treatment?
Adenomyosis and endometriosis frequently recur: in the first 5 years, the recurrence rate reaches 40%, and at more than 5 years — up to 74%. The process does not resume only in patients who have undergone radical surgical interventions.
Why can endometrial hyperplasia develop during mifepristone treatment?
Mifepristone is a potent progesterone inhibitor. With long-term administration of high doses of the drug, the absence of the natural antiproliferative effect of progesterone leads to hyperplastic processes in the mucous membrane of the uterus.
What else to study on this topic
- Theories of etiopathogenesis and classification of endometrioid disease.
- Clinical course and step-by-step diagnostic algorithm for adenomyosis.
- Diagnosis and surgical treatment of endometrioid ovarian cysts.
- Alternative management strategies for adenomyosis and strict indications for radical surgery.
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