Amenorrhea

1. Amenorrhea Khalid A. Yarouf 4MedStudents.com

2. Outline • Definitions. • Hx. • P/E. • Clinical approach to 1º amenorrhea. • Clinical approach to 2º amenorrhea.

3. Definitions • 1º Amenorrhea: = No menses by age 14 + absence of 2º sexual characteristics. = No menses by age 16 + presence of 2º sexual characteristics. • 2º Amenorrhea: = No menses for 3 months  if previous menses were regular. = No menses for 6 months  if previous menses were irregular

4. Hx: • Obstetric Hx: Gravidity, parity. • Gyne Hx: regularity of periods, duration, dysmenorrhea, menorrhagia, LMP.

5. P / E: • Tanner staging. • Breast present ? • Uterus present ? • PV exam. • Rule out possibility of pregnancy.

6. Clinical approach to 1º amenorrhea: No 2º sexual characteristics: • Clinical findings: • Absence of 2º sexual characteristics (e.g. breasts) must result from inadequate estrogen. Possible causes are: • Gonadal  Hyper-gonadotropic hypogonadism: • Pathophysiology: Normal hypothalamic-pituitary axis (indicated by ↑FSH), but end organ is unresponsive (absence of ovarian follicles  no estrogen).

7. Con’t • Cause is gonadal dysgenesis: • Commonest cause of 1º amenorrhea (30%). • Causes: Turner’s synd (46,X), structurally abnormal X chromosome, mosaicism with / without Y chromosome, pure gonadal dysgenesis (46,XX & 46,XY).

8. Con’t • Central Hypo-gonadotropic hypogonadism: • Pathophysiology: • Failure of GnRH secretion from hypothalamus: • Many pts with amenorrhea also have anosmia (Kallmann’s synd). • Failure of FSH secretion from anterior pituitary.

9. Con’t • Causes: CNS tumor, craniopharyngioma  FSH ↓. • Dx: • FSH differentiates between gonadal & central causes. • Karyotype is very useful as well. • Brain CT / MRI to rule out a tumor  in case of central cause.

10. Con’t • Mx: • In both conditions, give estrogen  stimulate 2º sexual development. • Cyclic progestins  prevent endometrial hyperplasia.

11. Con’t 2º sexual characteristics (e.g. breasts) are present: • Adequate estrogen must be produced by gonads to stimulate breast development. Genotype is normal 46,XX in most cases. • Causes: 1. Intact hymen. 2. Transverse obstructing vaginal septum. 3. Cervical agenesis: rare. 4. Uterine absence.

12. Con’t 4. Müllarian agenesis: • Idiopathic failure of müllarian ducts to descend into pelvis to form upper genital tract. Pts usually have bilateral rudimentary uterine anlagen, Fallopian tubes & ovaries. • 20% of cases of 1º amenorrhea.

13. Con’t • Dx Testosterone level & karyotype should be obtained.

14. Con’t • Mx: • Neovagina may need to be created. It’s effective in allowing normal vaginal intercourse. Breasts developed, but no pubic and axillary hair • 10% of cases of 1º amenorrhea.

15. Con’t • Present with evidence of gonadal secretion (breast development) but no manifestation of androgen secretion  reflects absence of androgen receptors (complete androgen insensitivity synd = testicular feminization synd is misnomer). • Genotype is 46,XY. The Y chromosome has led to production of Müllarian Inhibitory Factor (MIF), hence pts have only vaginal dimple & no uterus or tubes.

16. Con’t • Testes, which are often intra-abdominal, produce normal male levels of testosterone. Breast development is due to enzymatic conversion of testosterone to estrogen. • Mx: • Gonadal resection once puberty is complete. • Creation of neovagina when pt is prepared to be sexually active. • Psychotherapy.

17. Clinical approach to 2º amenorrhea • β-hCG level should be obtained:  rule out pregnancy (commonest cause of 2º amenorrhea). • Progesterone challenge  to assess estrogen status. • Medroxy-progesterone acetate 10 mg OD X 1 week  look for withdrawal bleeding:

18. Con’t • (+)ve test if any bleeding occurs within 2-7 days  always due to anovulation. • Do S-Prolactin & TSH  rule out correctable cause. e.g. pituitary prolactinomas / hypothyroidism. • Mx: • Treat underlying cause. • Periodic cyclic progestins prevent endometrial hyperplasia from unopposed estrogen. • Ovulation induction with Clomiphene citrate  if pregnancy is desired.

19. Con’t • (-)ve test if no bleeding occurs: •  hypo-estrogenism / outflow tract obstruction. • Combined Estrogen-Progesterone Challenge Test (EPCT) clarifies etiology of amenorrhea. • EPCT should be administered to see whether withdrawal bleeding occurs: • Conjugated estrogen 1.25 mg PO for 21 days followed by medroxy-progesterone acetate 10 mg PO X 1 week.

20. Con’t • (+)ve if any bleeding occurs within 2-7 days •  always due to lack of estrogen. • FSH level should be obtained to distinguish between hypothalamic-pituitary failure (↓ FSH) or ovarian failure (↑ FSH). In the former case, brain imaging should be obtained to rule out a tumor.

21. Con’t • Estrogen should be provided to prevent sequelae of estrogen deficiency, along with cyclic progestins to prevent endometrial hyperplasia, regardless of the specific cause. • (-)ve test if no bleeding occurs: •  always due to outflow tract obstruction. • Mx: Obtain hystero-salpingo-gram (HSG).  identify site of obstruction (e.g. cervical stenosis).  rule out endometrial adhesions (Asherman’s synd).