Amenorrhea

Normal physiologic circumstances: Arcuate nucleus releases pulses of luteinizing hormone-releasing (LHRH) into hypophyseal portal system approximately every hour. Discharge of LHRH releases luteinizing (LH) and follicle stimulating hormone (FSH) from the pituitary; LH and FSH in turn stimulate ovarian follicular growth and ovulation. Anovulation and Amenorrhea will occur as a result of interference with LHRH transport, LHRH pulse discharge, or congenital absence of LHRH(Kallmann,s syndrome). any of these situations will lead to hypogonadotropic hypogonadism.

Primary Amenorrhea: No menses by 14 years of age and absence of secondary sex characteristics. No menses by 16 years of age with presence of secondary sex characteristics. Secondary Amenorrhea: No menses for 3 months if previous menses were regular. No menses for 6 months if previous menses were irregular.

Importance of Amenorrhea: Cannot conceive due to no ovulation. Leads to osteoporosis and genital atropy. Increased endometrial hyperpalsia and carcinoma. Give rise to major social and psychosexual problems. Etiology and Pathogenesis: 1) Hypothalamic detects: Defects of GnRH transport Defects of GnRH pulse production Congenital absence of GnRH (Kallmanns syndrome) *Any of these situation will lead to Hypogonadotropic Hypogonadism 2) Pituitary defects: Acquired pituitary dysfunction. Sheehan,s syndrome, characterized by Postpartum Amenorrhea, results from pituitary necrosis secondary to severe hemorrhage and hypotension. Other causes may be iron deposition, high prolactin. 3) Ovarian failure: Primary ovarian failure is characterized by elevated Gonadotropins and low Estradiol. Secondary failure is almost due to hypothalamic dysfunction and is characterized by normal or low gonadotropins and low estradiol (hypergonadotropic hypogonadism). Steroid enzyme defects: Defects in enzymes 1-4, absence of breast development, the internal genitalia are normal, the karyotype is 46, XX. Ovarian resistance syndrome: Elevated LH and FSH, and the ovaries containingprimordial germ cells. A defect in the cell receptor mechanism is the presumed cause. Ovarian dysgenesis Premature ovarian failure: Menopause occurs before age 40.

4) Ovarian dysfunction 5) Uterine abnormality

Clinical approach to primary amenorrhea: 1) Breast are absent but a uterus is present: Inadequate Estrogen Clinical findings: Follicles are not present in the ovary to produce estrogen. Follicles may be present, but they are not being stimulated. Diagnosis: FSH level and karyotype should be obstained 1.Gonadal dysgenesis: FSH ; karyotype is 45 X (most common) 2.Hypothalamic-pituitary insufficiency: FSH ;karyotype is normal Management: HRT

2) Breast are present but a uterus is absent: Adequate estrogen Clinical findings: 1.Genetic female: Mullerian agenesis 46, XX; testosterone is at female levels 2.Genetic male: Androgen insensitivity 46, XY; testosterone is high male levels Management: Create a neovagina ERT 3) Breast are present and a uterus is present: Similar to secondary amenorrhea

Clinical approach to secondary amenorrhea: *(- HCG to rule out pregnancy) PCT (progesterone challenge test): Medroxyprogesterone acetate 10 mg PO for 1~7 days Positive: withdrawal bleeding occurs within 2~7 days Negative: no bleeding occurs PCT is positive Obtain serum prolactin and TSH levels Periodic progestin cycling Ovulation induction PCT is negative Inadequate estrogen or an outflow tract obstruction EPCT is necessary (combined estrogen-progesterone challenge test): conjugated estrogen 1.25 mg PO for 21 days followed by medroxyprogesterone acetate 10 mg PO for 10 7 days EPCT positive: Lack of Estrogen Withdrawal bleeding occurs within 2~7 days Low FSH: hypothalamic-pituitary failure High FSH: ovarian failure EPCT negative: outflow tract obs Outflow tract obstruction Endometrial adhesions ( Ashermans syndrome)