Gynaecology Pg No 81 -90

Menopause

• Menopause is the permanent cessation of menstruation in a woman of menopausal age who has experienced amenorrhea for at least 12 months.
• The average age of menopause worldwide is 51 years, while in India, it is 47 years.
• Premature menopause, now referred to as Primary Ovarian Insufficiency (POI), occurs before the age of 40 and is characterized by secondary amenorrhea and infertility.
• Late menopause, characterized by the non-occurrence of menopause in women aged 55 or older, requires an endometrial biopsy due to the increased risk of endometrial cancer.
• Perimenopause, previously known as climacteric, is a transitional phase leading to menopause, marked by hot flushes and an increase in cycle length by at least 7 days.
• Menopause is a clinical diagnosis, and no hormonal tests are required for confirmation.
• POI mandates laboratory tests for confirmation.

Hormonal Profile During Menopause

• Estrogen levels decrease during menopause.
• Estriol (E3) is the most common estrogen found in the body.
• Androgen levels decrease during menopause.
• Levels of Anti-Müllerian Hormone (AMH) and Inhibin decrease.
• Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels increase.

Physiology of Menopause

• Menopause is characterized by the apoptosis of ovarian follicles.
• The decrease in ovarian hormones leads to a loss of negative feedback on the pituitary gland.
• This results in an increase in FSH and LH levels.
• The elevated FSH and LH are excreted in the urine.
• Human Menopausal Gonadotropins (HMG) are extracted from the urine of postmenopausal women.

Hypergonadotropic Hypogonadism

• Secondary amenorrhea in combination with elevated FSH and LH levels indicates hypergonadotropic hypogonadism.
• The next diagnostic step is to measure estrogen levels.

Note

• Pregnancy is characterized by secondary amenorrhea accompanied by increased estrogen and progesterone levels.
• Elevated FSH levels and decreased LH levels indicate premature ovarian failure.

Hot Flashes/Flushes

• Vasomotor symptoms, including hot flashes, are the most common symptom of menopause.
• They are caused by a decrease in estrogen levels.
• Hot flashes are characterized by a sudden, intense heat-like feeling on the face, followed by sweating, often with accompanying palpitations or tachycardia.
• They are most frequent at night, known as night sweats, interfering with sleep.

Puberty and Precocious Puberty

Causes of Precocious Puberty

Central/True Precocious Puberty

• Idiopathic (most common).
• Brain tumors (10%): Hamartoma, Glioma, Ependymoma.
• Infection: TB meningitis.
• Continuous GnRH administration.
• GnRH antagonist use.

Peripheral Precocious Puberty

• Isosexual: Increased estrogen:
  • Granulosa cell tumor of the ovary.
  • Chronic hypothyroidism (due to similar alpha subunit of LH and FSH).
• Heterosexual: Increased androgen:
  • Androgen-producing tumor of the ovary.
  • Congenital Adrenal Hyperplasia (CAH).

Management of Precocious Puberty

• Treat the underlying cause.

McCune Albright Syndrome

• McCune Albright Syndrome is characterized by:
  • Café au lait spots.
  • Polyostotic fibrous dysplasia.
  • Precocious puberty.

Pathogenesis of McCune Albright Syndrome

• A mutation in the G-protein coupled receptors (FSH receptors) activates signaling pathways, leading to ovarian activation and increased estrogen levels.

Investigations for McCune Albright Syndrome

• Bone age estimation.
• FSH and LH levels (for differentiating between central and peripheral precocious puberty).
• Estrogen levels.
• Thyroid-Stimulating Hormone (TSH) levels.
• Magnetic Resonance Imaging (MRI) of the brain.
• Ultrasound (USG) of the pelvis and abdomen.

Investigations for Heterosexual Precocious Puberty

• Testosterone levels.
• Dehydroepiandrosterone sulfate (DHEA-S) levels (to determine the source: ovary or adrenals).
• 17-hydroxyprogesterone (17-OH progesterone) levels (to rule out Congenital Adrenal Hyperplasia (CAH).

Note

• Polycystic Ovarian Syndrome (PCOS) is the most common cause of heterosexual puberty development.
• Congenital Adrenal Hyperplasia (CAH) is the most common cause of heterosexual precocious puberty.

Hormone Replacement Therapy (HRT)

HRT - 1

Basis of HRT

• Postmenopausal symptoms are related to estrogen deficiency.
• Hormone Replacement Therapy (HRT) provides relief from menopausal symptoms.

Indications for HRT

• Postmenopausal women with severe hot flushes.
• Primary Ovarian Insufficiency (POI).
• Low estrogen conditions:
  • Turner's syndrome.
  • Swyer's syndrome.
  • Androgen Insensitivity Syndrome.
• Surgical oophorectomy.

Types of HRT

• Estrogen (E) only HRT: Used when the uterus is absent.
• Estrogen + Progesterone (E+P) HRT: Used when the uterus is present.

Mechanism of Action (MOA) of HRT

• Estrogen: Relieves hot flushes.
• Progesterone: Protects the endometrium from cancer development.

Minimum Duration of HRT

• Ideal duration: As long as estrogen is being administered.
• Minimum duration: 12 days per cycle.

Advantages and Disadvantages of HRT

Factors Associated with HRT

• HRT does not safeguard against Coronary Artery Disease (CAD) in women aged 60 or older.
• It doesn't increase the risk of cervical cancer.

HRT - 2

Most Commonly Used HRT

Estrogen

• 17β-Estradiol (DOC):
  • Route: Transdermal or oral.
  • Dose:
    • Oral: 1 mg/day, starting at 0.5 mg/day.
    • Transdermal: 0.05 mg/day, starting at 0.025 mg/day.
• Conjugated Equine Estrogen (CEE): Obsolete.

Progesterone

• Micronized oral P (DOC): Dose: 100-200 mg/day.
• Dydrogesterone (DOC).

Duration of Postmenopausal Therapy

• Maximum: 5 years.
• Up to menopausal age.

Indications of HRT

• Primary Ovarian Insufficiency (POI).
• Turner's syndrome.
• Swyer's syndrome.
• Absent uterus due to:
  • Hysterectomy due to endometrial cancer.
  • Endometriosis.
  • Endometroid tumor of the ovary.
  • Supracervical/Subtotal hysterectomy.

Contraindications of HRT

• History of Deep Vein Thrombosis (DVT), stroke, or Coronary Artery Disease (CAD).
• History of breast cancer.
• Undiagnosed vaginal bleeding (endometrial cancer).
• Acute liver biopsy.
• Hypertriglyceridemia (Absolute C/D).
• Severe uncontrolled hypertension (HTN).

Important Points Regarding HRT

• No contraceptive benefit.
• Estrogen + Mirena: Contraceptive benefit in perimenopausal women experiencing hot flushes.
• Indications for Fluoxetine (DOC) for hot flushes:
  • Age < 60 years.
  • Onset of menopause < 10 years ago.
  • Hot flushes present and HRT contraindicated.

General Gynecology

Menopause-Related Symptoms

• Experienced by perimenopausal and menopausal women.
• Appear 3-4 years before menopause.
• Subside automatically within 5 years after menopause.
• Correspond to the time of LH surge.
• Symptoms:
  • Severe hot flushes.
  • Sleep disturbances.
  • Interference with daily routines.
• Only indication for postmenopausal HRT.

Osteoporosis

• Definition: Quantitative bone defect.
• ↓ Bone Mineral Density (BMD) primarily affects trabecular bone.
• ↓ Estrogen leads to ↓ bone mass.

Clinical Features of Osteoporosis

• Patient complains of backache.
• Increased risk of fractures.
• Fracture types:
  • Vertebral fracture (T12-L3).
  • Neck of femur fracture.
  • Colles fracture.

Diagnosis of Osteoporosis

• Indication: Age ≥ 65 years.
• Site: 1st to 4th lumbar vertebrae and neck of femur.
• BMD Measurement:
  • T-score: Patient's BMD compared to a young woman’s.
  • Z-score: Patient’s BMD compared to a woman of the same age.

Treatment of Osteoporosis

• DOC (Drug of Choice): Bisphosphonates.
  • Mechanism: Affect osteoblasts.
  • Examples:
  • Teriparatide.
  • Strontium.

Risk of Coronary Artery Disease (CAD)

• Estrogen's Cardioprotective Role:
  • ↑ HDL (High-density lipoprotein).
  • ↓ LDL (Low-density lipoprotein).
  • ↑ NO (Nitric Oxide) in vascular endothelial cells.
• ↓ Estrogen at menopause leads to ↑ CAD.
• Incidence of CAD depends on:
  • Comorbidities.
  • Smoking habits.

Management of Hot Flashes

Osteoporosis Treatment

Senile Vaginitis Treatment

Calcium and Vitamin D Requirements

Primary Ovarian Insufficiency

• Causes:
  • Chemotherapy/radiotherapy (ovaries are the most radiosensitive pelvic organ).
  • Galactosemia.
  • Mumps.
  • Autoimmune diseases.
• Exhaustion of ovarian follicles before the age of 40 (premature menopause).

Role of Hormone Replacement Therapy (HRT)

• HRT is never given to prevent CAD.
• In women aged 60 or older, HRT slightly increases the risk of CAD (E+P HRT > estrogen-only HRT).
• HRT has no effect on the risk of CAD in women younger than 60.

Senile/Atrophic Vaginitis

• New term: Genitourinary syndrome of menopause.
• Caused by a decrease in cervical discharge leading to vaginal dryness.

Symptoms of Senile Vaginitis

Urinary Symptoms

• Increased frequency of urination.
• Dysuria.
• Frequent urinary tract infections (UTIs).
• Urinary incontinence.

Genital Symptoms

• Dyspareunia.
• Postmenopausal vaginal bleeding (due to atrophic vagina).

Local Examination Findings in Senile Vaginitis

• Shiny vaginal mucosa.
• Loss of vaginal rugosities.
• Thin, atrophied vaginal mucosa.

Note

• Commonly used Selective Estrogen Receptor Modulators (SERMs):
  • Clomiphene.
  • Tamoxifen.
  • Raloxifene (can lead to vaginal dryness).
• SERMs that can be used to manage senile vaginitis:
  • Ospemifene.
  • Bazedoxifene + estrogen.

Physiology of Androgens

• Intrauterine life:
  • Adrenal glands produce androgens.
  • Aromatase converts androgens to estrogen.
• Normal levels: < 70 ng/dl.
• Steroid: C19 steroid.
• Receptors: Intracytoplasmic.
• Acts on: Intranuclear receptors.
• Binds: Sex Hormone Binding Globulin (SHBG) > Albumin.

Effect of Androgens on SHBG

• Androgens: ↓ SHBG.
• Estrogen: ↑ SHBG.

Androgens in Females

• Produced by the ovary:
  • Androstenedione.
  • Testosterone.
  • Dehydroepiandrosterone (DHEA).
• Not produced by the ovary (exclusively produced by adrenal glands):
  • Dehydroepiandrosterone Sulphate (DHEA-Sulphate).
  • Dihydrotestosterone (DHT).

Functions of Androgens in Females

• Pubarche: Growth of pubic and axillary hair.
• Increased libido.

Note

• Androgens in theca cells are converted to estrogen by aromatase in granulosa cells, promoting follicle growth.
• Excessive androgens in granulosa cells are folliculotoxic.

Effects of Excessive Androgens in Females

• Folliculotoxic.
• Inhibits follicle growth and maturation.
• Anovulation.
• Hirsutism.
• Virilization.