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Monday, August 18, 2025

Periods (irregular)


Irregular Periods (Menstrual Irregularities)

Introduction

Menstruation is a fundamental biological process governed by the hypothalamic-pituitary-ovarian (HPO) axis, involving hormonal interplay between gonadotropins, ovarian hormones, and endometrial responsiveness. A normal cycle is defined as occurring every 21–35 days, lasting 3–7 days, with average blood loss of 30–40 mL.

When cycles deviate significantly in timing, duration, or flow, the condition is termed irregular periods. Clinically, this is referred to as abnormal uterine bleeding (AUB) if outside expected norms. Depending on presentation, irregular menstruation may take the form of:

  • Oligomenorrhea: cycles longer than 35 days.

  • Polymenorrhea: cycles shorter than 21 days.

  • Metrorrhagia: bleeding between cycles.

  • Menometrorrhagia: prolonged or heavy bleeding occurring irregularly.

  • Amenorrhea: complete absence of menses.

Irregular periods can be transient, benign, or indicative of serious systemic or gynecological conditions.

Causes of Irregular Periods

1. Physiological Factors

  • Adolescence: anovulatory cycles common in the first 1–2 years after menarche.

  • Perimenopause: ovarian reserve declines, cycles become erratic before menopause.

  • Pregnancy: although usually results in amenorrhea, some women may have irregular spotting.

  • Lactation: prolactin suppresses ovulation, causing irregular or absent periods.

2. Lifestyle Influences

  • Psychological stress: suppresses GnRH pulsatility.

  • Excessive exercise (athletic amenorrhea): high-intensity training alters gonadotropin release.

  • Eating disorders / low body weight: reduced leptin disrupts hypothalamic signaling.

  • Obesity: causes anovulation and hyperestrogenism.

3. Gynecological and Endocrine Disorders

  • Polycystic Ovary Syndrome (PCOS): hyperandrogenism, insulin resistance, and chronic anovulation.

  • Endometriosis: ectopic endometrial tissue causes irregular bleeding and dysmenorrhea.

  • Uterine fibroids or polyps: structural abnormalities disturb endometrial shedding.

  • Thyroid dysfunction: both hypo- and hyperthyroidism affect menstruation.

  • Hyperprolactinemia: pituitary adenomas elevate prolactin, suppressing GnRH.

  • Premature Ovarian Insufficiency (POI): early depletion of ovarian function.

4. Medications

  • Hormonal contraception (combined oral contraceptives, implants, injections, intrauterine systems) can cause breakthrough bleeding.

  • Antipsychotics/antidepressants: elevate prolactin.

  • Anticoagulants: heavy and irregular bleeding.

  • Chemotherapy: premature ovarian failure.

Pathophysiology

The HPO axis maintains menstrual regularity:

  1. GnRH pulses from the hypothalamus stimulate pituitary release of LH and FSH.

  2. FSH recruits ovarian follicles → estradiol production.

  3. LH surge triggers ovulation.

  4. Progesterone stabilizes endometrium during luteal phase.

Disruptions at any level (central hypothalamic control, pituitary secretion, ovarian function, endometrial receptivity) result in irregular bleeding.

Clinical Presentation

  • Unpredictable timing of cycles (too early, too late, skipped).

  • Variations in flow: unusually heavy (menorrhagia) or scanty (hypomenorrhea).

  • Intermenstrual bleeding.

  • Associated symptoms:

    • Acne, hirsutism, obesity → PCOS.

    • Galactorrhea → hyperprolactinemia.

    • Heat/cold intolerance → thyroid disease.

    • Pelvic pain → endometriosis or fibroids.

    • Hot flushes, vaginal dryness → premature ovarian insufficiency.

Diagnostic Evaluation

1. History

  • Menstrual pattern (cycle length, duration, heaviness).

  • Obstetric and contraceptive history.

  • Stress, diet, exercise, weight fluctuations.

  • Drug use (hormonal, psychiatric, anticoagulants).

  • Family history (thyroid disease, PCOS, early menopause).

2. Physical Examination

  • BMI, waist-to-hip ratio.

  • Signs of androgen excess.

  • Thyroid enlargement.

  • Breast exam (galactorrhea).

  • Pelvic exam: uterine size, adnexal masses.

3. Investigations

  • Pregnancy test (hCG): first-line in reproductive age.

  • Blood tests:

    • FSH, LH, estradiol → ovarian function.

    • Prolactin → pituitary cause.

    • TSH, free T4 → thyroid.

    • Testosterone, DHEAS → PCOS or adrenal causes.

    • HbA1c, fasting insulin → metabolic evaluation in PCOS.

  • Imaging:

    • Pelvic ultrasound: PCOS morphology, fibroids, polyps.

    • MRI brain: suspected pituitary adenoma.

  • Endometrial biopsy: women >35 years with abnormal bleeding (rule out malignancy).

Management and Treatment

1. General Lifestyle Measures

  • Weight normalization: even 5–10% loss in obese women restores ovulation.

  • Balanced diet, regular but not excessive exercise.

  • Stress reduction.

2. Specific Treatments

a) Polycystic Ovary Syndrome (PCOS)

  • Lifestyle modification: diet, exercise, weight loss.

  • First-line pharmacologic therapy:

    • Combined oral contraceptives (COCs): regulate cycles, reduce androgen symptoms.

      • Example: ethinylestradiol 30 µg + levonorgestrel 150 µg daily for 21 days, followed by 7-day break.

    • Metformin hydrochloride: improves insulin sensitivity and restores ovulation.

      • Typical dose: 500–850 mg orally 2–3 times daily with meals.

  • Ovulation induction for fertility:

    • Clomiphene citrate: 50 mg orally daily for 5 days starting day 2–5 of cycle.

    • Letrozole: 2.5–5 mg orally daily for 5 days starting day 3–5 of cycle (increasingly preferred over clomiphene).

b) Thyroid Disorders

  • Hypothyroidism:

    • Levothyroxine sodium: initial 25–50 µg orally daily, titrate by TSH response.

  • Hyperthyroidism:

    • Carbimazole: 10–40 mg/day orally in divided doses.

    • Propylthiouracil: 50–150 mg orally 2–3 times daily.

c) Hyperprolactinemia

  • Dopamine agonists:

    • Bromocriptine: 1.25–7.5 mg/day orally.

    • Cabergoline: 0.25–1 mg orally twice weekly.

d) Uterine Fibroids / Polyps

  • Medical:

    • Tranexamic acid: 1 g orally 3–4 times daily during heavy bleeding days.

    • NSAIDs (ibuprofen, mefenamic acid): ibuprofen 400 mg orally every 6–8 hours for pain and bleeding reduction.

  • Hormonal:

    • COCs or progestogen therapy (medroxyprogesterone acetate 10 mg orally for 10–14 days each month).

    • Levonorgestrel intrauterine system (LNG-IUS): 20 µg/day release for up to 5 years.

  • Surgical: myomectomy, polypectomy, hysterectomy if severe.

e) Endometriosis

  • Pain and cycle control:

    • NSAIDs: e.g., ibuprofen 400 mg orally every 6–8 hours.

    • Hormonal suppression: COCs, progestins (dienogest 2 mg orally daily).

    • GnRH agonists: leuprolide acetate 3.75 mg intramuscular monthly.

f) Premature Ovarian Insufficiency (POI)

  • Hormone Replacement Therapy (HRT):

    • Estradiol valerate: 1–2 mg orally daily.

    • Medroxyprogesterone acetate: 10 mg orally for 10–14 days per cycle.

  • Fertility options: assisted reproduction using donor oocytes.

Pharmacological Summary (Generic Names and Doses)

  • Ethinylestradiol + levonorgestrel: 30 µg/150 µg daily for 21 days + 7-day break.

  • Metformin hydrochloride: 500–850 mg orally 2–3 times daily.

  • Clomiphene citrate: 50 mg daily × 5 days (cycle days 2–5).

  • Letrozole: 2.5–5 mg daily × 5 days (cycle days 3–5).

  • Levothyroxine sodium: 25–50 µg daily, titrated.

  • Carbimazole: 10–40 mg/day orally.

  • Propylthiouracil: 50–150 mg orally 2–3 times/day.

  • Bromocriptine: 1.25–7.5 mg/day orally.

  • Cabergoline: 0.25–1 mg twice weekly.

  • Tranexamic acid: 1 g orally 3–4 times/day during menstruation.

  • Ibuprofen: 400 mg orally every 6–8 hours.

  • Mefenamic acid: 500 mg orally every 8 hours.

  • Dienogest: 2 mg orally daily.

  • Leuprolide acetate: 3.75 mg IM monthly.

  • Estradiol valerate: 1–2 mg orally daily.

  • Medroxyprogesterone acetate: 10 mg orally for 10–14 days/month.

  • LNG-IUS: 20 µg/day release (device inserted intrauterine).

Complications

  • Infertility (chronic anovulation in PCOS, POI).

  • Endometrial hyperplasia and carcinoma (unopposed estrogen in anovulatory cycles).

  • Iron-deficiency anemia (from heavy irregular bleeding).

  • Psychological stress from unpredictable cycles.

  • Osteoporosis (hypoestrogenism in POI or prolonged GnRH agonist use).

Prognosis

  • Adolescents: cycles usually normalize within 1–2 years.

  • PCOS: chronic, but symptoms controlled with therapy.

  • Thyroid or prolactin-related: good prognosis if underlying cause corrected.

  • Fibroids/endometriosis: may require long-term management or surgery.

  • POI: irreversible, but HRT improves quality of life.

Preventive and Supportive Measures

  • Balanced diet, maintain healthy weight.

  • Regular moderate exercise.

  • Avoid extreme dieting and overtraining.

  • Manage stress through counseling, meditation, or therapy.

  • Routine gynecological check-ups, especially in women with persistent irregular cycles >3 months.





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