Lynestrenol

Approved Indications:

• Secondary Amenorrhea:
  For the treatment of secondary amenorrhea due to functional hypothalamic-pituitary-ovarian axis disturbance.
• Menstrual Disorders:
  Management of irregular menstruation, dysfunctional uterine bleeding, oligomenorrhea, and polymenorrhea.
• Endometriosis:
  Treatment of endometriosis by suppressing ovulation and inducing amenorrhea.
• Menstrual Cycle Control:
  Used for delaying menstruation in specific clinical or personal circumstances.

Off-label or Clinically Accepted Uses:

• Contraception:
  Used as a progestogen-only oral contraceptive in certain formulations and clinical settings.
• Pubertal Menorrhagia:
  Management of heavy menstrual bleeding in adolescents under medical supervision.
• Hormone Replacement Therapy (HRT):
  Used in combination with estrogen to prevent endometrial hyperplasia in postmenopausal women.

Adults:

• Menstrual Disorders or Secondary Amenorrhea:
  5–10 mg orally once daily for 10 days per cycle. Withdrawal bleeding usually occurs within 2–4 days after stopping.
• Endometriosis:
  5–10 mg orally once daily continuously or cyclically for 6 months or more, depending on clinical response.
• Menstrual Delay:
  5 mg orally once or twice daily starting 3 days before expected menstruation and continued as needed.
• Contraception (Off-label use):
  5 mg orally once daily, taken continuously at the same time each day.

Adolescents (≥16 years):

• May be used under medical supervision for conditions such as pubertal menorrhagia.

Elderly:

• Not indicated for postmenopausal women.

Hepatic Impairment:

• Contraindicated in moderate to severe liver dysfunction due to hepatic metabolism.

Renal Impairment:

• Use with caution; no specific dose adjustment required unless clinically indicated.

Administration Route:

• Oral (tablet)

Administration Instructions:

• Take with water, preferably at the same time each day.
• If a dose is missed, take it as soon as remembered; do not double the dose.

Lynestrenol is a synthetic progestin derived from 19-nortestosterone. It is a prodrug that is converted in the liver to norethisterone, its active metabolite. Norethisterone binds to progesterone receptors in the uterus, pituitary, and hypothalamus. This interaction inhibits the mid-cycle luteinizing hormone (LH) surge, suppressing ovulation. Additionally, it transforms the proliferative endometrium into a secretory form, stabilizing the endometrial lining and reducing irregular bleeding. In endometriosis, it suppresses estrogen-stimulated endometrial tissue growth, providing symptom relief.

• Absorption: Rapid and efficient oral absorption
• Bioavailability: High, with significant first-pass hepatic metabolism
• Distribution: Widely distributed; binds extensively to plasma proteins
• Metabolism: Hepatically metabolized to norethisterone (active form)
• Elimination: Primarily via urine and feces as inactive metabolites
• Half-life: Approximately 8–12 hours
• Onset of Action: Therapeutic effect achieved within several days; endometrial response typically occurs in 7–10 days

• Pregnancy:
• Contraindicated during pregnancy
• May interfere with normal hormonal regulation of pregnancy and carry potential risks due to androgenic activity
• Lactation:
• Excreted in small amounts into breast milk
• Generally considered acceptable for short-term use in breastfeeding, but long-term use should be assessed by a healthcare professional

• Primary Class: Progestogen
• Subclass: 19-nortestosterone derivative
• Category: Oral synthetic progestin for hormonal regulation and gynecological use

• Hypersensitivity to Lynestrenol or any of its excipients
• Pregnancy (known or suspected)
• Severe hepatic impairment or active liver disease
• History of thromboembolic disorders (e.g., DVT, PE)
• Undiagnosed abnormal vaginal bleeding
• Known or suspected estrogen- or progesterone-sensitive malignancies (e.g., breast or endometrial cancer)

• Thromboembolic Events:
  Increased risk in individuals with personal or family history of thrombosis, smokers, or those with prolonged immobilization
• Liver Function:
  Discontinue use if jaundice or liver enzyme elevations occur
• Psychiatric Effects:
  Monitor patients for signs of depression or mood changes
• Menstrual Irregularities:
  Amenorrhea, spotting, or breakthrough bleeding may occur, particularly in long-term use
• Metabolic Effects:
  Monitor glucose in diabetic patients and watch for weight gain or fluid retention
• Monitoring Requirements:
  Regular clinical review, particularly in long-term users, including breast examinations and liver function tests

Common:

• Irregular bleeding, spotting, or amenorrhea
• Breast tenderness
• Nausea or gastrointestinal discomfort
• Acne or oily skin
• Headache
• Mood changes or irritability

Less Common:

• Weight gain
• Fluid retention
• Decreased libido
• Fatigue

Rare but Serious:

• Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism)
• Hepatic dysfunction
• Hypersensitivity reactions (e.g., rash, urticaria)

Timing & Severity:

• Most effects occur during the first few months and are mild
• Serious effects are rare but require immediate medical attention

• CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin):
  May reduce effectiveness of Lynestrenol by increasing its metabolism
• Antibiotics (e.g., rifampin):
  May impair contraceptive reliability
• Oral Anticoagulants (e.g., warfarin):
  Monitor INR closely as Lynestrenol may alter anticoagulant effect
• Cyclosporine:
  Lynestrenol may increase serum cyclosporine levels

Enzyme System:

• Primarily metabolized by CYP3A4

• Lynestrenol continues to be recognized in European gynecological guidelines as an effective oral progestin for treating menstrual disorders and endometriosis
• Emphasis on short-term use to minimize progestin-related side effects
• No recent changes to approved indications or major regulatory warnings reported

• Temperature: Store below 25°C (77°F)
• Humidity & Light: Keep in a dry place; protect from moisture and direct sunlight
• Handling Instructions:
• Keep out of reach of children
• Do not use if the tablets are damaged or past expiry
• Reconstitution/Refrigeration: Not required (solid oral dosage form)