amenorrhea
DESCRIPTION
Amenorrhea. UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series. Objectives for Amenorrhea. Define amenorrhea and oligomenorrhea Explain the pathophysiology and identify the etiologies of amenorrhea and oligomenorrhea - PowerPoint PPT PresentationTRANSCRIPT
AmenorrheaUNC School of Medicine
Obstetrics and Gynecology ClerkshipCase Based Seminar Series
Objectives for Amenorrhea
Define amenorrhea and oligomenorrhea
Explain the pathophysiology and identify the etiologies of amenorrhea and oligomenorrhea
Describe the symptoms and physical examination findings of amenorrhea and oligomenorrhea
Discuss the steps in the evaluation and management of amenorrhea and oligomenorrhea
Describe the consequences of untreated amenorrhea and oligomenorrhea
Amenorrhea – absence of menses Primary amenorrhea – absence of menarche
Absence of menarche by age 14 without secondary sexual characteristics Absence of menarche by age 16 with secondary sexual characteristics
Secondary amenorrhea – absence of menses in a previously menstruating woman
Absence of menses for > 6 months or duration of 3 menstrual cycles
Oligomenorrhea – reduction in frequency of menses Cycle lengths > 35 days, but < 6 months
Definition
Pregnancy Thyroid disease Hyperprolactinemia
Prolactinoma Hypergonadotropic hypogonadism
Gonadal dysgenesis (i.e. Turner syndrome) Premature ovarian failure
Hypogonadotropic hypogonadism Constitutional delay of puberty Congenital GnRH deficiency (Kallman syndrome) Functional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa) CNS tumor (i.e. Craniopharyngioma)
Normogonadotropic Congenital (i.e. Mullerian agenesis, Androgen Insensitivity syndrome) Outflow tract obstruction (i.e. Imperforate hymen, Transverse vaginal septum) Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease)
Primary Amenorrhea: Etiology
Most common etiologies: Chromosomal abnormalities causing gonadal dysgenesis – 50% Hypothalamic hypogonadism – 20% Absence of the uterus, cervix, or vagina – 15% Transverse vaginal septum or imperforate hymen – 5% Pituitary disease – 5%
Primary Amenorrhea: Etiology
Primary Amenorrhea: History
Findings Association
Completion of stages of puberty? Development of axillary and pubic hair? Breast development?
Ovarian or pituitary failureChromosomal abnormality
Family history of delayed or absent puberty? Familial disorderConstitutional delay of puberty
Height relative to family members? Turner’s syndrome
Symptoms of virilization? PCOSOvarian or adrenal tumorPresence of Y chromosome
Recent stress? Change in weight, diet, or exercise? Functional hypothalamic amenorrhea
Medications (i.e. antidepressants, antipsychotics)? Hyperprolactinemia
Galactorrhea? Hyperprolactinemia
Headaches, visual field defects, fatigue, polyuria or polydipsia?
Hypothalamic-pituitary disease
Evaluation of pubertal development (height, weight) and growth chart Breast development (Tanner staging) Evaluation for features of Turner’s syndrome
Webbed neck, low hair line, shield chest, widely spaced nipples Examine skin for hirsutism, acne, striae, increased pigmentation, and
vitiligo
Pelvic exam Clitoral size Intactness of hymen Depth of vagina Presence of vaginal septum Presence of cervix, uterus, and ovaries
Primary Amenorrhea: Physical Exam
Tanner Stages
Stage 1: Prepubertal, no palpable breast tissue or pubic hair.
Stage 2: Development of breast bud; sparse, straight pubic hair.
Stage 3: Enlargement of breast; pubic hair darker, coarser, and curlier.
Stage 4: Areola and papilla project above the breast; pubic hair adult-like in appearance.
Stage 5: Recession of areola to match contour of breast; pubic hair extends to thigh.
Figure from: Roede, MJ, van Wieringen, JC. Growth diagrams 1980: Netherlands third nation-wide survey. Tijdschr Soc Gezondheids 1985; 63:1. Reproduced with permission from the author.
Primary Amenorrhea: Evaluation
Secondary sexual characteristics present?
Measure FSH Perform ultrasound of uterus
Karyotype analysis
FSH > 20 Uterus absent or abnormal
Uterus present or normal
Turner’s syndrome
Hypergonadotropichypogonadism
Hypogonadotropichypogonadism
46,XX
FSH < 5
46,XY
Premature ovarian failure
Karyotype analysis
46,XX 45,XO
Müllerian agenesis
Androgen insensitivity syndrome
Outflow obstruction
Imperforate hymenTransverse vaginal
septum
Evaluate for 2° amenorrhea
No Yes
No Yes
Hypothalamic amenorrhea Constitutional delay
of puberty Kallman syndrome CNS tumor
PCOS Cushing’s
Pregnancy Thyroid disease Hyperprolactinemia
Prolactinoma Breastfeeding, Breast stimulation Medication (i.e. Antipsychotics, Antidepressants)
Hypergonadotropic hypogonadism Postmenopausal ovarian failure Premature ovarian failure
Hypogonadotropic hypogonadism Functional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa) CNS tumor (i.e. Craniopharyngioma) Sheehan’s syndrome Chronic illness
Normogonadotropic Outflow tract obstruction (i.e. Asherman’s syndrome, Cervical stenosis) Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease, CAH)
Secondary Amenorrhea/Oligomenorrhea: Etiology
Most common etiologies: Ovarian disease – 40% Hypothalamic dysfunction – 35% Pituitary disease – 19% Uterine disease – 5% Other – 1%
Secondary Amenorrhea/Oligomenorrhea: Etiology
Secondary Amenorrhea/Oligomenorrhea: History
Findings Association
Recent stress? Change in weight, diet, or exercise? Functional hypothalamic amenorrhea
Development of acne, hirsutism, striae, central obesity, increased skin pigmentation or deepening voice?
PCOSCushing’s diseaseOvarian or adrenal tumor
Medications (i.e. antidepressants, antipsychotics)? Hyperprolactinemia
Chronic illness? Functional hypothalamic amenorrhea
Headaches, visual field defects, fatigue, polyuria or polydipsia?
Hypothalamic-pituitary disease
Symptoms of estrogen deficiency (hot flashes, vaginal dryness, decreased libido, or poor sleep)?
Premature ovarian failurePostmenopausal ovarian failure
Galactorrhea? Hyperprolactinemia
History of obstetrical catastrophe, severe bleeding, D&C, endometritis, or other infection?
Sheehan’s syndromeAsherman’s syndrome
General Evaluation of height, weight, and BMI Examine skin for hirsutism, acne, striae, acanthosis nigricans, thickness or
thinness, and easy bruisability
Thyroid exam Breast exam
Express for galactorrhea
Pelvic exam Atrophy Vaginal dryness
Secondary Amenorrhea/Oligomenorrhea: Physical
Exam
Secondary Amenorrhea/Oligomenorrhea:
EvaluationNegative urine pregnancy test
Progestin challenge test
Negative MRIConsider other
causes
No withdrawal bleed
Prolactin < 100 ng/mL Prolactin > 100 ng/mL
Check FSH
Estrogen/progestinChallenge test
Normogonadotropichypogonadism
Hypergonadotrpoic hypogonadism
Withdrawal bleed
FSH > 20 IU/LOutflow obstruction
• Medication
MRI to evaluate for pituitary tumor
Normal MRIHypogonadotropic
hypogonadism
MRI to evaluate for prolactinoma
Both normal Normal TSH, Abnormal prolactin
Hyperandrogenic anovulation
PCOS Cushing’s
Check TSH and prolactin
Normal prolactin,Abnormal TSH
Thyroid disease
No withdrawal bleed Withdrawal bleed
FSH < 5IU/L
Asherman’s Cervical stenosis
Ovarian failure
Medication
Hypothalamic amenorrhea
Chronic illness
Progestin challenge test Medroxyprogesterone acetate 10 mg daily for 10 days IF withdrawal bleed occurs – Not outflow tract obstruction IF no withdrawal bleed occurs – Estrogen/Progestin challenge test
Estrogen/Progestin challenge test Oral conjugated estrogen 0.625 – 2.5 mg daily for 35 days Medroxyprogesterone acetate 10 mg daily for 26-35 days IF no withdrawal bleed occurs – Endometrial scarring
Hysterosalpingogram or Hysteroscopy to evaluate endometrial cavity
Secondary Amenorrhea/Oligomenorrhea:
Evaluation
Evaluation of hyperandrogenism Symptoms: hirsutism, acne, alopecia, masculinization, and virilization Differential diagnosis:
Adrenal disorders: Atypical congenital adrenal hyperplasia (CAH), Cushing’s syndrome, Adrenal neoplasm
Ovarian disorders: PCOS, Ovarian neoplasms Lab: Testosterone, DHEA-S, 17α-hydroxyprogesterone
Secondary Amenorrhea/Oligomenorrhea:
Evaluation
Hormone Level Indication
Testosterone < 200 ng/dL PCOS
> 200 ng/dL Evaluate for adrenal or ovarian tumor
DHEA-S < 700 ng/dL PCOS
> 700 ng/dL Evaluate for adrenal or ovarian tumor
17α-hydroxyprogesterone
> 4 ng/mL Consider ACTH stimulation test to diagnose CAH
Treatment should be directed at… Correcting the underlying pathology Helping woman to achieve fertility (IF desired) Preventing the complications of disease process
Consequences of untreated amenorrhea/oligomenorrhea: Hypoestrogenism – Osteoporosis, Infertility Hyperestrogenism – Heart disease, Stroke, Diabetes Mellitus, Breast cancer
(controversial), Endometrial hyperplasia and Endometrial cancer
Amenorrhea/Oligomenorrhea: Management
Amenorrhea/Oligomenorrhea: Management
Diagnosis Management
Ovarian insufficiency Premature ovarian failure Postmenopausal ovarian failure
Hormone replacement therapy (HRT)
*Congenital anatomic lesions Surgical correction
*Presence of Y chromosome (i.e. AIS) Gonadectomy
*Gonadal dysgenesis (i.e. Turner syndrome) Estrogen + progestin, growth hormoneIVF (IF pregnancy desired)
Hyperprolactinemia Dopamine agonist (Bromocriptine, Cabergoline)
Functional hypothalamic amenorrhea Increase caloric intake > energy expenditure
Hypothalamic or pituitary dysfunction (non-reversible)
OCP’s, pulsatile GnRH or exogenous gonadotropins
CNS tumor Craniopharyngioma Prolactinoma
Surgical resectionMicroadenoma (< 10mm) – Dopamine agonist Macroadenoma (>10mm) – Trans-sphenoidal resection
PCOS OCP’s, weight loss, and metformin
Asherman’s syndrome Hysteroscopic lysis of adhesions
*Causes of primary amenorrhea only
Bottom Line Concepts A thorough history and physical examination as well as laboratory testing can
help narrow the diagnosis of amenorrhea.
In patients with primary amenorrhea, the presence or absence of sexual development should direct evaluation.
Constitutional delay of puberty is a diagnosis of exclusion.
The definitive method to identify hypothalamic-pituitary dysfunction is to measure FSH and prolactin levels.
If the patient has abnormal uterine development, a karyotype analysis should be performed to diagnose müllerian agenesis versus chromosomal abnormalities.
In a patient with secondary amenorrhea, pregnancy should be ruled out prior to further workup.
Treatment goals of amennorrhea and oligomenorrhea include prevention of complications such as osteoporosis, endometrial hyperplasia and heart disease; preservation of fertility; and in primary amenorrhea, progression of normal pubertal development.
References and Resources
APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 43 (p92-93).
Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 35 (p315-319).
Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 32 (p355-363).
Master-Hunter T, Helman DL. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006 Apr 15; 73(8): 1374-82.