bubble_chart Overview

Perimenopausal syndrome (climacteric syndrome) refers to a comprehensive set of symptoms and physical manifestations caused by psychological, neuroendocrine, and metabolic changes during menopause, affecting various organ systems. The aging of the human lifespan is a significant trend in modern society. Consequently, the health care and disease prevention for perimenopausal and postmenopausal women have become crucial tasks for gynecologists and society as a whole.

bubble_chart Clinical Manifestations

The advanced stage of menopause primarily manifests as vasomotor syndrome; in the advanced stage (>5 years), various aging-related diseases of organ systems gradually appear.

I. Symptoms related to estrogen deficiency

(1) Vasomotor syndrome: The incidence rate is 75–85% within 1–5 years after menopause. For those who undergo bilateral oophorectomy before the age of 25, the incidence rate is 76% within 1–6 weeks.

Vasomotor syndrome refers to a symptom complex characterized by paroxysmal episodes of hot flashes, flushing, spontaneous sweating, and palpitation, caused by estrogen deficiency and autonomic nervous dysfunction. Flushing typically begins on the face, neck, and anterior chest, then spreads to the lower abdomen, trunk, and limbs, accompanied by skin vasodilation, patchy erythema, elevated temperature, headache, dizziness, palpitation, dysphoria, and dry mouth. To dissipate heat, patients often remove clothing, bare their arms, open windows, use fans, or go outdoors. The flushing lasts 3–4 minutes, followed by sweating, vasoconstriction, and normalization of body temperature, ending the episode. The average episode cycle is 54±10 minutes. Nocturnal episodes often abruptly awaken the patient from sleep with great dripping sweating, soaking clothes and bedding, accompanied by insomnia and anxiety. The next day, the patient may experience mental confusion, forgetfulness, nausea, vomiting, vertigo, and other discomforts.

Mechanism of hot flashes: ① The GnRH neurons in the hypothalamic preoptic area have direct synaptic and neural connections with adjacent thermoregulatory neurons, so changes in GnRH neuron function affect the latter. ② Postmenopausal estrogen deficiency feedback increases norepinephrine activity, stimulating GnRH release, which activates the heat-loss mechanism via neural connections. Hot flashes are related to fluctuations in GnRH and norepinephrine activity. ③ Reduced dopaminergic and β-endorphinergic activity in the central nervous system and hypothalamus.

(2) Aging-related diseases of organ systems

1. Regression of sexual characteristics and genital atrophy: Dryness of the vulva, loss of pubic hair, white lesions, vulvar cutaneous pruritus, secondary infections, decreased sexual function, bladder and rectal prolapse, prolapse of uterus, etc. Some women exhibit masculinization symptoms such as hirsutism, seborrhea, and acne.

2. Breast atrophy and sagging, fading of nipple and areola pigmentation: Reduced breast firmness and tissue laxity.

3. Skin and mucous membranes: Dryness, wrinkles, hair loss, pigmentation, age spots, and susceptibility to skin diseases. Dry mouth, pharyngitis, and hoarseness.

4. Cardiovascular system: Includes hypertension, stirred pulse, arteriosclerosis, and coronary heart disease. The incidence of thromboembolic diseases increases with age postmenopause. The incidence of coronary heart disease in women ≤55 years is 5–8 times lower than in men of the same age.

II. Psychiatric and neurological systems: Menopausal women are prone to depression, forgetfulness, obsessive thoughts, paranoia, emotional inversion, mood instability, persecutory delusions, anxiety, suspicion, paresthesia, feelings of incompetence, and suicidal ideation. Some may exhibit mania, thought disorder, and schizophrenia.

III. Increased susceptibility to tumors: Related to diminished immune surveillance and aging. Statistics show that the incidence of gynecological tumors increases with age, e.g., ≥40 years: 219.93–245.39/100,000; ≥50 years: 433.82–450.45/100,000; ≥60 years: 770.84–782.14/100,000; ≥70 years: 1120.71–1129.90/100,000; ≥80 years: 1495.09–1657.08/100,000 (New York State, 1960). The peak incidence of cervical carcinoma, endometrial cancer, and ovarian cancer occurs between 40–60 years. The age range for invasive cervical cancer is 41.8–48.7 years (Noda, 1983). The gender ratio for urological tumors: ≤40 years, M:F = 1:0.6; 40–60 years, 1:1. Among these, kidney cancer has a ratio of 2:1, while urethra cancer is 1:3–5, especially in women ≥50 years.

IV. Urinary System Frequent urination, urgency, stress or urge incontinence (urgent incontinence). Urethral mucosal prolapse, urethral caruncle, nephroptosis, hydronephrosis-ureteral dilation, and susceptibility to urinary retention and infection.

V. Musculoskeletal System Bone and joint (wrist, elbow, shoulder, hip, and lower back), ligaments, muscle atrophy, soreness, dysfunction, osteoporosis, and susceptibility to fracture. For details, see the section on osteoporosis.

VI. Endocrine and Metabolic Changes

(1) Hyperlipidemia: Manifested as increased cholesterol, LDL, TG, and VLDL, while HDL and HDL ₂ are decreased, leading to a higher risk of atherosclerosis and hypertension.

(2) Prediabetic tendency: Caused by reduced insulin secretion from β-cells and increased insulin resistance in peripheral tissues.

(3) Edema: May be due to hypothyroidism-induced myxedema, angioneurotic edema, or hypoalbuminemia and nutritional deficiency-related edema.

(4) Weakened immune function: Increased susceptibility to infections and tumors.

VII. A significant increase in cardiovascular disease incidence occurs 10–15 years after oophorectomy. For example, among those aged 45–55, the female-to-male ratio of cardiovascular disease is 4.29:2.29; coronary heart disease 3.78:2.73; and cerebrovascular disease 3.89:0.32. The incidence in women is significantly higher than in men of the same age. The osteoporosis rate is four times that of men of the same age (Taro Tamada, 1982). In natural menopause, the incidence shows no significant gender difference from age 65. Women who experience menopause before age 40 develop coronary heart disease earlier, with an incidence rate 2.4 times higher than those who have not yet reached menopause.

VIII. Premenopausal Oophorectomy and Perimenopausal Syndrome The earlier premenopausal women undergo bilateral oophorectomy, the sooner and more frequently ovarian deficiency symptoms appear, with more pronounced manifestations. For those who undergo oophorectomy before age 25, estrogen deficiency symptoms appear within 1–6 weeks postoperatively, with an incidence of 76%, whereas in those aged ≥40, symptoms appear only after 6–18 months.

Retaining one ovary carries a 13.7% probability of secondary benign tumors and an 8.2% risk of malignancy, typically occurring an average of 5.8 years post-surgery.

Postmenopausal women who undergo oophorectomy also experience decreased plasma T, A, and E levels, but the resulting hormonal deficiency symptoms are less noticeable. Based on the above analysis, whether in premenopausal or postmenopausal women, a cautious approach should be taken regarding the decision to preserve or remove ovaries affected by benign sexually transmitted disease-related changes.

bubble_chart Diagnosis

1. Medical History Carefully inquire about menstruation history, marital and childbearing history, age at menopause, and timing of ovarian and uterus removal. Note any history of postmenopausal bleeding, family history (heart and blood vessel diseases, diabetes, tumors), and medical history (hormones and medications).

2. Physical Examination Conduct a comprehensive physical examination. Pay attention to the presence of heart and blood vessel diseases, liver and kidney diseases, obesity, edema, malnutrition, and mental-neurological functional status. Gynecological examination should routinely include cervical cytology, and check for any inflammatory or tumorous conditions of the reproductive organs. For those with postmenopausal bleeding, perform fractional curettage and endometrial biopsy. For abnormal cytology results, conduct multiple cervical biopsies and endocervical curettage. For enlarged ovaries, rule out tumors. Routine breast examination is also necessary.

3. Special Examinations Perform as indicated.

(1) Hormone Assays: Include hormone measurements of the HPO axis, adrenal axis, thyroid axis, and pancreatic function.

(2) Blood Chemistry: Include blood calcium, phosphorus, blood sugar, blood lipids, BUN, liver and kidney function tests. Urine sugar and urine protein. Ca⁺⁺/C, hydroxyproline/C ratio.

(3) Medical Imaging: Focus on diagnosing osteoporosis. Include bone density measurements, single/multi-beam absorption measurements of cortical bone thickness, neutron activation analysis, CT, and MRI scans.

bubble_chart Treatment Measures

I. Hormone Therapy: Estrogen/Progestin Replacement Therapy.

(1) Indications: Vasomotor syndrome, osteoporosis, atrophic vaginitis, premature menopause, recurrent or refractory urethro-cystitis; lipoproteinaemia.

(2) Contraindications: History of embolism, chronic hepatic or renal insufficiency, hormone-dependent tumors (uterine fibroids, endometrial cancer, breast cancer, ovarian cancer), porphyria, severe hypertension, diabetes, severe varicose veins, heavy smoking, inability to adhere to long-term follow-up.

(3) Methods: Oral administration is recommended, while subcutaneous implants and intramuscular injections are discouraged. Topical application is limited to senile vaginitis and should not be used long-term.

1. Estrogen-Progestin Cyclic Therapy: The standard replacement regimen. Conjugated estrogens 0.625mg/d × 25 days (or equivalent doses of other estrogens), supplemented with secretory-phase doses of progestin for 10 days from days 16–25. One course consists of 3–6 cycles. For those with periodic withdrawal bleeding, progestin should continue to be supplemented. If no withdrawal bleeding occurs for 3 consecutive cycles, progestin may be discontinued.

2. Estrogen-Only Cyclic Therapy: Estrogen replacement doses taken for 25 days per month. Limited to women who have undergone hysterectomy with significant menopausal symptoms. For those without hysterectomy but with negative progesterone withdrawal bleeding, estrogen-only therapy may still be attempted, but progesterone withdrawal bleeding must be induced every 2–3 months. Those with positive withdrawal bleeding should switch to estrogen-progestin cyclic therapy. If progesterone withdrawal bleeding remains negative for 3 consecutive cycles, estrogen-only cyclic therapy may continue, but in principle, it should not exceed 3–6 cycles.

3. Nylestriol Therapy: Suitable for all menopausal women. 5mg, taken orally once a month. After symptom improvement, reduce to 1–2mg once or twice monthly, with a total efficacy rate of 75.8–98.4% (Lu Xiangyun, 1984). Advantages: simple, long-acting, minimal endometrial stimulation. Significant improvement in senile vaginitis and urethritis symptoms.

4. Estrogen-Androgen Therapy: Suitable for women with breast pain or decreased sexual function. Estrogen combined with methyltestosterone 5–10mg/d, sublingual. Also inhibits estrogen-induced endometrial hyperplasia.

(4) Efficacy

1. Estrogen-progestin therapy significantly improves psychosomatic symptoms, with a total efficacy rate of 84–97%. Efficacy in reducing hot flashes: estrogen-only 96%, estrogen-progestin 95%, estrogen-androgen 91%, progestin-only ≥56%. Headache relief rate: estrogen or estrogen-androgen 93%.

2. Estrogen therapy markedly improves osteoporosis, reducing fracture rates from 50–70% to 3%. Androgen or anabolic steroid therapy maintains a fracture rate of 40%. However, after discontinuing estrogen, fracture rates rise again to 25%. During estrogen therapy, urinary Ca⁺⁺/C and hydroxyproline/C ratios decrease, further declining with progestin supplementation, highlighting the importance of estrogen-progestin therapy.

3. Estrogen-progestin cyclic therapy: 97% of women experience periodic bleeding, which may persist until age 60. Among those treated at 60–65, 60% still experience withdrawal bleeding, though the amount gradually diminishes. Some maintain normal withdrawal bleeding even after 17 years of treatment.

(5) Side Effects: Gastrointestinal side effects correlate with estrogen dose and formulation, but tolerance is generally good. To minimize side effects, follow individualized principles, using the lowest effective dose and tapering or discontinuing upon symptom resolution.

(6) Monitoring and Follow-up: The focus is on preventing excessive endometrial hyperplasia and cancerous changes, mammary gland hyperplasia reactions, and systemic metabolic abnormalities. All patients receiving hormone replacement therapy should undergo outpatient review or correspondence follow-up every 3 months, gynecological examination every 6 months, and ultrasound and endometrial biopsy as necessary. Breast examination should pay attention to the presence of lobular hyperplasia or masses, and monitoring of heart, liver, gallbladder, and blood functions should also be conducted.

II. Pharmacotherapy Includes: α₂ receptor agonists, β-adrenergic blockers, sedative-anxiolytics, and antidepressants, among others.

Clonidine, an imidazoline derivative and α₂ receptor agonist, is a centrally acting antihypertensive that also effectively reduces flushing episodes, particularly for nocturnal episodes, night sweats, and insomnia. The initial dose is 0.075mg three times daily, which can be gradually increased to 0.45–0.9mg/day. Side effects include dizziness, drowsiness, and dry mouth.

β-adrenergic blockers, such as labetalol, can alleviate palpitations. Sedatives like diazepam and phenobarbital, as well as antidepressants such as imipramine and doxepin, are used only when significant psychiatric or neurological symptoms are present.

Calcium supplements, vitamin D, calcitonin, and fluoride, in combination with hormonal therapy, can effectively slow the progression of osteoporosis and reduce fracture rates. For details, refer to the section on osteoporosis.

III. Mental and Psychological Health Care and Prevention of Systemic Diseases

The physical and mental health care of menopausal women is a societal responsibility. Efforts should include public health education and preventive measures, establishing health consultation clinics, regular health check-ups, and proactive prevention and treatment of psychosomatic diseases common during menopause. Early diagnosis and treatment of cardiovascular diseases, osteoporosis, endocrine and metabolic disorders, and tumors are essential. Encouraging menopausal women to engage in self-care can help reduce the incidence of perimenopausal syndrome.