Menopausal hormone therapy

Goals and personalization principles

The main guideline in managing patients with menopausal syndrome is an individual approach (recommendation grade C, evidence level 5). Therapy aims at effective symptom relief and reduction or postponement of long-term consequences of estrogen deficiency.

For safe treatment, the concept of the "window of therapeutic opportunity" is taken into account. The optimal time to start is the perimenopausal and early postmenopausal period. Systemic therapy should be considered if the woman's age is under 60 years and less than 10 years have passed since the onset of postmenopause. An exception is genitourinary syndrome of menopause (GSM): there are no age restrictions for prescribing local estrogen therapy (estriol).

The choice of dose, dosage form, and administration regimen is made taking into account age, reproductive aging stage, gynecological diseases, comorbid conditions, and the woman's own preferences. The therapeutic goal is to use the most appropriate minimum effective dose strictly in the presence of indications and absence of contraindications.

Breast screening before MHT initiation

Exogenous estrogens, which are part of preparations for the treatment of menopausal syndrome and oral contraceptives, are considered a risk factor for breast cancer (BC). This requires mandatory screening before prescribing hormone treatment.

The examination algorithm includes visual inspection and palpation. Instrumental diagnostics depends on age:

• Under 40 years: breast ultrasound is performed.
• 40 years and older: mammography in two projections with BI-RADS assessment and ACR density classification is indicated.

If the patient has high mammographic tissue density (ACR type C or D), the sensitivity of mammography drops to 48%. In such situations, additional ultrasound is mandatory.

Indications for consultation with an oncomammologist before starting therapy include: the presence of nodular formations, a BI-RADS category other than 1 or 2, high density (ACR C or D), and other significant risk factors for breast cancer.

Differential diagnosis and genetics of breast cancer

If a malignant neoplasm is suspected, differential diagnosis with benign processes must be performed. Breast sarcoidosis clinically presents as a dense painless mass; biopsy reveals multiple non-caseating granulomas (tuberculosis must be ruled out). Idiopathic granulomatous mastitis on mammograms yields focal asymmetry, skin thickening, and axillary lymphadenopathy, making it very difficult to distinguish from cancer.

Hereditary cancer syndromes play a special role. Mutations in BRCA1 and BRCA2 genes link breast cancer with other tumors. For example, in ovarian cancer (high-grade serous and endometrioid carcinomas), the frequency of BRCA mutations reaches 15%. Their presence indicates high sensitivity of the tumor to platinum agents, alkylating drugs, and PARP inhibitors. In pancreatic cancer, the hereditary breast and ovarian cancer syndrome occurs in 10% of cases; the presence of BRCA1, BRCA2, or PALB2 mutations makes platinum-based chemotherapy regimens preferable.

Antineoplastic therapy: limitations and side effects

If a patient is diagnosed with breast cancer, systemic antineoplastic therapy is prescribed taking into account strict contraindications. These include pregnancy (for most cytostatics and radiation therapy), decompensated concomitant diseases, severe myelosuppression, and severe organ failure. Heart failure is especially significant when planning treatment with anthracyclines and anti-HER2 drugs due to their cardiotoxicity.

Typical side effects depend on the treatment method:

• Chemotherapy: myelosuppression, nausea and vomiting, alopecia, mucositis, peripheral neuropathy, cardiotoxicity.
• Radiation therapy: radiation dermatitis, tissue fibrosis, arm lymphedema (when regional zones are irradiated).
• Hormone therapy: antiestrogens (tamoxifen) can cause hot flashes, increase the risk of thromboembolic complications and endometrial hyperplasia; aromatase inhibitors often provoke osteoporosis and arthralgia.

Class and exam questions

What else to study on this topic

• Criteria for assessing breast lesions using the BI-RADS system.
• ACR classification of mammographic breast density.
• Mechanisms of action of PARP inhibitors in BRCA-associated tumors.
• Pathogenesis of genitourinary syndrome of menopause (GSM) and the role of estriol.
• Cardiotoxicity of anthracyclines and anti-HER2 therapy: monitoring and prevention.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.