Menopause

The menopause is the natural phase in a woman’s life when menstruation permanently stops, typically between the ages of 45 and 55. It occurs due to a decline in the production of estrogen and progesterone by the ovaries.

Common Symptoms During Menopause

During peri- and postmenopause, women may experience symptoms that vary in intensity. The most common symptoms include:

  • Hot Flashes: Sudden sensations of heat, often accompanied by sweating.
  • Sleep Disturbances: Difficulty falling or staying asleep, often linked to nighttime hot flashes.
  • Mood Swings: Irritability, nervousness, and depressive moods can occur.
  • Dry Mucous Membranes: Especially vaginal dryness, which may cause discomfort during intercourse due to estrogen deficiency.
  • Bone Loss (Osteoporosis): Lower estrogen levels reduce bone density, increasing the risk of fractures.
  • Cardiovascular Problems: Hormonal decline increases the risk of heart and vascular diseases.
  • Decreased Sexual Desire: Loss of libido is a common symptom.

Hormonal Changes:

Menopause is characterized by a decline in the two main hormones: estrogen and progesterone. At the same time, the levels of FSH (follicle-stimulating hormone) and LH (luteinizing hormone) rise significantly as the body attempts to compensate for the decreased ovarian function. These hormonal changes are responsible for the typical menopausal symptoms.

Estrogen Changes – Role of Estrone

  • In postmenopausal women, the dominant circulating estrogen is estrone.
  • There is a shift in the estrone-to-estradiol ratio in favor of estrone.
  • Unlike estradiol, estrone is not bound to SHBG (sex hormone-binding globulin).

Factors Influencing Estrone Levels:

  1. Alcohol Consumption, Obesity, and Fatty Liver Disease: These can increase estrone levels. In obese women, estrone can stimulate endometrial growth, potentially leading to abnormal bleeding.
  2. PCOS (Polycystic Ovary Syndrome): Estrone levels are elevated in women with PCOS.
    • Approximately 50% of estrone production in obese women and those with PCOS comes from subcutaneous fat tissue.
  3. Source of Estrone During Menopause:
    • Around 95% of estrone is produced in the adrenal glands from androstenedione, as functional ovarian follicles and granulosa cells are lost during menopause.

Therapy Options:

  1. Hormone Replacement Therapy (HRT):
    • Relieves symptoms and protects against osteoporosis.
    • For women with a uterus, estrogen is combined with progesterone to prevent endometrial cancer.
  2. Non-Hormonal Treatments:
    • Herbal supplements, antidepressants, and lifestyle adjustments to manage symptoms like hot flashes and sleep issues.
  3. Lifestyle Changes:
    • Regular exercise, balanced diet, and stress management.

 

Pros and Cons of HRT:

Pros:

  • Relieves menopausal symptoms
  • Protects against osteoporosis
  • May reduce the risk of colorectal cancer

Cons:

  • Slightly increased risk of:
    • Breast cancer
    • Thrombosis (blood clots)
    • Cardiovascular diseases, especially with combined estrogen-progesterone therapy

HRT should always be tailored to individual needs and administered at the lowest effective dose under medical supervision.

Hormone Replacement Therapy (HRT) and Estrone

  • During oral hormone replacement therapy, estrogens are converted into estrone in the liver.
  • Elevated estrone levels can cause symptoms like breast tenderness and fluid retention.
  • In such cases, switching to natural estrogens delivered via the skin (transdermal application) is recommended to avoid high estrone concentrations.

The menopausal transition is a natural part of aging, but the symptoms can significantly impact quality of life. Lifestyle changes, non-hormonal treatments, and individualized hormone replacement therapy can effectively manage symptoms and long-term health risks.

Medical Measures

To alleviate menopause symptoms, various treatment options are available:

  1. Hormone Replacement Therapy (HRT):
    • The most effective treatment to relieve menopausal symptoms. Estrogen is administered, and progesterone is added if the woman still has a uterus.
  2. Non-Hormonal Therapies:
    • Herbal supplements (e.g., soy isoflavones), antidepressants, or medications to reduce hot flashes.
  3. Lifestyle Changes:
    • A balanced diet, regular exercise, and stress management techniques (e.g., yoga, meditation) help alleviate symptoms.
  4. Vaginal Estrogen Therapy:
    • For women with vaginal dryness, local estrogen creams or suppositories can be used.

Implementation of Hormone Replacement Therapy (HRT)

For women who have undergone a hysterectomy (surgical removal of the uterus), estrogen therapy alone is typically administered, as there is no longer a risk of endometrial cancer. HRT is primarily used to relieve menopausal symptoms or prevent osteoporosis.

Common Estrogen Preparations and Dosages

  1. Oral Preparations (Tablets):
    • Estradiol (Estrofem®, Progynova®):
      • Dosage: 1–2 mg daily (adjusted based on symptoms; usually starting with the lowest effective dose).
    • Conjugated Estrogens (Premarin®):
      • Dosage: 0.3–0.625 mg daily, depending on symptom severity.
  2. Transdermal Preparations (Patches, Gel):
    • Estradiol Patches (Estradot®, Climara®):
      • Dosage: 25–100 µg daily.
      • Patches are usually replaced once or twice weekly.
    • Estradiol Gel (Estreva®, Divigel®):
      • Dosage: 0.5–1.5 mg daily applied to the skin (thighs or arms).
  3. Vaginal Preparations (for local symptoms):
    • Estradiol Cream (Ovestin® Cream):
      • Dosage: 0.5 g daily (0.5 mg estriol) initially, then 1–2 applications per week.
    • Estradiol Vaginal Rings (Estring®):
      • Releases 2 mg estradiol over 90 days.
    • Estradiol Suppositories (Vagifem®):
      • Dosage: 10 µg daily for the first two weeks, then 1–2 suppositories per week.

Treatment Strategy and Individual Adjustment

  • Start with Low Dosage: The therapy typically begins with the lowest effective dose to minimize side effects. Dosage adjustments depend on symptoms like hot flashes, sleep disturbances, or vaginal dryness.
  • Regular Monitoring: Regular follow-up with a physician is essential to adjust therapy, monitor risks, and determine the therapy’s duration.

Progesterone for Women with a Uterus

To reduce the risk of endometrial cancer in women with an intact uterus, progesterone is added to estrogen therapy.

  1. Oral Progesterone:
    • Medroxyprogesterone Acetate (Provera®):
      • Dosage: 5–10 mg daily for 10–14 days per month (cyclic) or 2.5 mg daily (continuous).
    • Micronized Progesterone (Utrogest®, Prometrium®):
      • Dosage: 100–200 mg daily (cyclic or continuous).
  2. Combined Estrogen-Progestogen Therapy:
    • Estradiol + Dydrogesterone (Femoston®):
      • Dosage: 1 mg estradiol + 10 mg dydrogesterone daily.
    • Estradiol + Norethisterone Acetate (Kliofem®, Activelle®):
      • Dosage: 1 mg estradiol + 0.5 mg norethisterone acetate daily.
  3. Levonorgestrel-Releasing IUD (Mirena®):
    • Provides local progesterone to protect the endometrium while systemic estrogen is administered.

Cyclic vs. Continuous HRT

  • Cyclic HRT: Estrogen is taken daily, and progesterone is added for 10–14 days monthly, causing a withdrawal bleed.
  • Continuous Combined HRT: Both estrogen and progesterone are taken daily, avoiding withdrawal bleeding. This is often preferred in postmenopausal women.

Risks and Benefits of HRT

Benefits:

  1. Relief from menopausal symptoms (hot flashes, night sweats, vaginal dryness).
  2. Prevention of osteoporosis and reduction of fracture risk.
  3. Possible reduced risk of colon cancer.
  4. Improved quality of life.

Risks:

  1. Breast Cancer: Combined HRT increases the risk after prolonged use (>5 years).
  2. Thrombosis: HRT raises the risk of venous thrombosis and pulmonary embolism.
  3. Cardiovascular Diseases: Slightly higher risks of heart attack and stroke, especially with late initiation after menopause.
  4. Endometrial Cancer: Estrogen-only therapy raises the risk of uterine cancer unless combined with progesterone.

Conclusion

The decision to start HRT should be individualized, weighing the woman’s symptoms, health risks, and benefits.

  • Short-term HRT (3–5 years) is considered safe for managing menopausal symptoms when initiated early in menopause.
  • Long-term HRT is associated with higher risks and should be used with caution.

Regular medical monitoring is essential to adjust treatment and minimize risks.