Amenorrhea Dr Jack Biko

introduction A symptom and not a Condition Absence of menstrual bleeding Maturation of H-P-O axis Outflow tract

Causes Hypothalamic Pituatory Ovarian Other

Amenorrhea Primary Secondary Absence of menses by age 16 with normal secondary sexual characteristics Absence of menses by age 14 without secondary sexual development Secondary Absence of menses for 6 months in a previously menstruating female, not on contraceptives There is a 5% lifetime incidence for some form of amenorrhea. Physiologic causes of amenorrhea are: Prepubertal status, pregnancy, lactation, and menopause

Amenorrhea Transient, intermittent or permanent Dysfunction of hypothalamus, pituatory gland, ovaries, uterus or vagina Thyroid gland Adrenal gland

Hormonal events

Events of Puberty Thelarche (breast development) Requires estrogen Pubarche/adrenarche (pubic hair development) Requires androgens Menarche Requires: GnRH from the hypothalamus FSH and LH from the pituitary Estrogen and progesterone from the ovaries Normal outflow tract

Teens with Secondary sexual characteristics present No menstruation Cyclical pains THINK MULLERIAN ANOMALIES / OBSTRUCTION OF OUTFLOW TRACT

Primary Amenorrhea Is there normal development of secondary sexual characteristics? YES Think Pregnancy Mullerian anomaly – outflow tract, uterine Androgen insensitivity With androgen insensitivity, there will typically be more breast development than pubic hair development.

Primary amenorrhea CNS pathology Ovarian - Genetic abnormality Obstruction of outflow tract

Are there secondary sexual characteristics?

Think hypogonadism or hypogonadotropism Primary Amenorrhea Is there normal development of secondary sexual characteristcs? NO Think hypogonadism or hypogonadotropism

Mayer-Rokitansky-Kuster-Hauser Syndrome (utero-vaginal agenesis) 15% of primary amenorrhea Normal secondary development & external female genitalia Normal female range testosterone level Absent uterus and upper vagina & normal ovaries Karyotype 46-XX 15-30% renal, skeletal and middle ear anomalies

Imperforate Hymen

Amenorrhea with Immature Secondary Characteristics FSH Serum level /Low normal High Hypogonadotropic hypogonadism Gonadal dysgenesis

Gonadal Dysgenesis Chromosomally abnormal - Classic turner’s syndrome (45XO) - Turner variants (45XO/46XX),(46X-abnormal X) - Mixed gonadal dygenesis (45XO/46XY) Chromosomally normal - 46XX (Pure gonadal dysgeneis) - 46XY (Swyer’s syndrome)

Androgen Insensitivity Normal breasts but no sexual hair Normal looking female external genitalia Absent uterus and upper vagina Karyotype 46, XY Male range testosterone level Treatment : gonadectomy after puberty + HRT

Amenorrhea Evaluation Pregnancy test Physical exam to determine presence of uterus FSH Karyotype

Amenorrhea Treatment Cyclic estrogen/progestin Remove gonadal streaks if XY or mosaic Increased (52%) risk of gonadoblastomas, dysgerminomas, and yolk sac tumors Pulsatile GnRH for ovulation induction in select patients Surgical resection of intrauterine, cervical, and vaginal septa

Secondary Amenorrhea Pregnancy! CNS disorders Pituitary gland Thyroid Ovary Uterus Systemic disorders Renal failure, liver disorders, DM Medications: anti-psychotics, reserpine

Secondary Amenorrhea CNS disorders Chronic hypothalamic anovulation Stress Increased exercise levels Anorexia nervosa Head trauma Space-occupying lesions

Secondary Amenorrhea Pituitary resection Sheehan’s syndrome Hyperprolactinemia: Prolactinoma Medications Renal failure Pituatory injury Pituitary resection Sheehan’s syndrome Thyroid disorders Hyper- or hypothyroidism

Secondary Amenorrhea Ovulation disorders Polycystic ovarian syndrome Premature ovarian failure Uterine abnormalities Asherman’s syndrome Cervical stenosis Drug-induced amenorrhea Hormonal contraceptives GnRH analogues

PCOS First described in 1935 Findings of polycystic ovaries reported more than 100yrs previously A syndrome – no single feature or test is diagnostic

Endocrinology of PCOS Hyper-production of androgens by theca cells. Abnormal ovarian steroid-genesis Failure of follicular maturation. Lack of progesterone production due to corpus luteum absence. Subsequent increase of LH level.

Diagnostic Criteria; Rotterdam 2003 Based on Consensus Oligo or anovulation Hyperandrogenism – clinical or biochemical Polycystic ovaries Exclude other causes of androgen excess

Intra-uterine adhesions Asherman’s syndrome Previous D&C Previous endometritis Endometrial TB

Asherman’s Syndrome

Treatment Hysteroscopic resection High dose oestradiol

Hysteroscopy

Amenorrhea History Nutrition/exercise habits, weight change Sexual/contraceptive practice History of uterine/cervical surgery Physical exam Height/weight Hirsutism Galactorrhea Estrogen status of tissues Laboratory BhCG PRL & TSH  progesterone challenge  FSH  if high karyotype Karyotype for patients with premature ovarian failure <30yo If hirsutism is present, consider PCOS, congenital adrenal hyperplasia, Cushing’s, or ovarian tumors: check free testosterone

Secondary Amenorrhea Treatment goals Discovery and treatment of underlying disorder Hormone replacement Menses every 1-3 months Pregnancy Ovulation induction FSH/LH Purpose for inducing menses at least every 3 months is to prevent endometrial hyperplasia and cancer

Case studies

12 year old No periods No pain No secondary sexual characteristics

15 yr old No periods Cyclical pains Has secondary sexual characteris

24 yr old G3P0 TOP x 3 No periods for 6 months now

33 yr old Amenorrhea for 4 yrs Para 0 No cyclical pains Normal secondary sexual characteristics

Amenorrhea 26 yr Gravida 0 with menarche at age 14 presents with one-year history of amenorrhea. Obese Hirsutism

Thank you