Duke Internal Medicine Residency Curriculum
Amenorrhea and
Postmenopausal Bleeding
Kim Zuzak
Jamie Todd
Kerry Hildreth
Erin Dunnigan
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Objectives
• Amenorrhea
– Definition and classification
– Causes
– Algorithm for approach to diagnosis, treatment
• Postmenopausal bleeding
– Definition
– Causes
– Approach to diagnosis
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Case #1
HPI: 32yo F history of HTN presents with absence of menses for 4 months.
She is concerned that something is “terribly wrong”. Her cycles were
previously normal and she has not been sexually active for several years.
On further history and ROS she states she has felt quite jittery lately and
feels that her concentration is impaired. She admits to slight weight loss.
Meds: HCTZ 25mg po daily
PE: T 37.0, BP 132/70, P 112 and regular
Thin, but well nourished female who appears anxious and fidgety
CV – tachycardic, but regular, no murmurs
Pulmonary and abdominal exam unremarkable
Neuro – normal with the exception of brisk DTRs
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Case #1Question
The most likely cause of the patient’s amenorrhea is?
A) Polycystic ovarian syndrome
B) Hyperprolactinemia
C) Hyperthyroidism
D) Asherman’s syndrome
E) Anxiety disorder
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Case #1 Answer
The most likely cause of the patient’s amenorrhea is?
A) Polycystic ovarian syndrome
B) Hyperprolactinemia
C) Hyperthyroidism
D) Asherman’s syndrome
E) Anxiety disorder
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Amenorrhea: Definitions and Classifications
• Primary amenorrhea
– No menarche by age 16
– Due to congenital or karyotype abnormalities
– Uncommon, generally present to pediatricians
• Secondary amenorrhea
– Absence of menses for 3 months in setting of
previously normal menstruation
– Absence of menses for 9 months in setting of
oligomenorrhea
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Causes of Secondary Amenorrhea
• Pregnancy (most common)
• Thyroid disease
• Hyperprolactinemia
• Normogonadotropic amenorrhea (outflow tract
obstruction or hyperandrogenic anovulation)
• Hypergonadotropic hypogonadism
• Hypogonoadotropic hypogonadism
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Causes of Secondary Amenorrhea: Hyperprolactinemia
• Prolactin <100mcg/L
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Medications
Breastfeeding or breast stimulation
Substance abuse (cocaine, opiates)
Altered metabolism (renal or liver failure)
Ectopic production (renal cell or bronchogenic carcinoma,
teratoma)
• Prolactin >100mcg/L
– Pituitary adenoma
– Empty sella syndrome
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Causes of Secondary Amenorrhea: Normogonadotropic
• Hyperandrogenic anovulation
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Polycystic ovarian syndrome
Androgen secreting tumor
Congenital adrenal hyperplasia
Acromegaly
Cushing’s disease
Exogenous androgens
• Outflow tract obstruction
– Asherman’s syndrome
• Intrauterine scarring from infection or curettage
– Cervical stenosis
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Causes of Secondary Amenorrhea: Hypergonadotropic
• Menopausal ovarian failure
• Premature ovarian failure (increased FSH & LH)
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Autoimmune
Chemotherapy
Idiopathic
Mumps
Pelvic radiation
Genetic
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Causes of Secondary Amenorrhea: Hypogonadotropic
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Anorexia or bulimia nervosa
Excessive exercise
Excessive weight loss
Excessive psychosocial stressors
Sheehan’s syndrome
Chronic illness
CNS tumor
Cranial radiation
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Evaluation of Secondary Amenorrhea
Secondary Amenorrhea, Negative betaHCG
Check TSH and Prolactin
Prolactin <100mcg/L
Prolactin >100mcg/L
Abnormal TSH
Normal Prolactin
Consider alternate
causes of hyperprolactinemia
MRI to evaluate for
pituitary adenoma
Thyroid disease
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Evaluation of Secondary Amenorrhea
Secondary Amenorrhea, Negative betaHCG
Check TSH and Prolactin
Both Normal
Progesterone challenge
Withdrawal Bleed
Normogonadotropic Hypogonadism
No Withdrawal Bleed
Estrogen/progesterone challenge
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Evaluation of Secondary Amenorrhea
Estrogen/progesterone Challenge
Withdrawal Bleed
No Withdrawal Bleed
Check FSH/LH
FSH>20 and LH>40
Outflow Obstruction
FSH and LH <5
Hypergonadotropic
Hypogonadism
MRI for pituitary adenoma
If negative, then Hypogonadotropic
Hypogonadism
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Estrogen/Progesterone Challenge
• Use Medroxyprogesterone acetate
(provera) for progesterone withdrawal
bleed. 10mg po daily x 7-10 days. (other
options include norethindrone,
progesterone im, progesterone gel)
• Use combined oral contraceptive for
combined estrogen/progesterone
challenge.
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Case #2
62yo F with a history of diabetes mellitus presents to her
PCP with vaginal bleeding. She went through menopause
at age 51 and has never been on HRT. She is now
surprised to note that she has had intermittent spotting
over the past month. It does not seem related to
intercourse and she denies any trauma. Her last pap
smear was 6 months ago and showed no atypia.
Meds: Metformin, Lisinopril, ASA, Atorvastatin
PE: T 37.0 BP 140/82 P 72 BMI 32.2
Pelvic with normal vaginal mucosa, no adenexal mass,
cervix appears normal, no blood at the os
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Case #2 Question
The most appropriate next step in diagnosing the etiology
of this patient’s vaginal bleeding would be?
A) Perform a cervical biopsy
B) Proceed to hysteroscopy
C) Check PTT and PT
D) Proceed to transvaginal ultrasound
E) Schedule an endometrial biopsy
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Case #2 Answer
The most appropriate next step in diagnosing the etiology
of this patient’s vaginal bleeding would be?
A) Perform a cervical biopsy
B) Proceed to hysteroscopy
C) Check PTT and PT
D) Proceed to transvaginal ultrasound
E) Schedule an endometrial biopsy
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Postmenopausal Bleeding: Definitions
• Postmenopausal bleeding
– Patients not on HRT:
• Any bleeding ≥ 12 months after last menses
– Patients on HRT:
• Any unexpected bleeding ≥ 12 months on HRT
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Causes of Postmenopausal Bleeding
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Endometrial cancer
Atrophy
Endometrial hyperplasia
Endometrial polyps
Hormone effect
• ~90-95% of cases are due to benign causes
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Causes of Postmenopausal Bleeding: Endometrial Cancer
• Most common gyn cancer in women > 45
• ~5-10% of cases of postmenopausal bleeding
• Risk factors
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Nulliparity
Age
Diabetes mellitus
Obesity
Tamoxifen use
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More Common Causes of Postmenopausal Bleeding
• Atrophy is most common cause: ~ 40-60% of cases
• Mechanism: Hypoestrogenism leads to endometrial/vaginal
atrophy. This leads to a thin surface susceptible to bleeding.
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Endometrial hyperplasia (~10%)
– Caused by exposure to unopposed estrogen
– Presence of atypia correlated with progression to endometrial
cancer
• Endometrial polyps (~12%)
– Estrogen responsive
– More common peri or early menopause
• Hormone effect (~7%)
– Pattern depends on regimen used
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Evaluation of Postmenopausal Bleeding
• Transvaginal ultrasound
– Endometrial thickness ≤ 5 mm
• LR+ 2.8 (95% CI 1.66-4.55)
• LR- 0.18 (95% CI .07-.46)
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Endometrial thickness > 5mm
Increased echogenicity
Persistent bleeding
Inadequate visualization
Endometrial
Biopsy
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Evaluation of Postmenopausal Bleeding
• Endometrial Biopsy
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Allows tissue sampling
Simple procedure; no anesthesia
Samples 5-15% of endometrial surface
May miss small lesions
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Evaluation of Postmenopausal Bleeding
• If TVUS and biopsy non-diagnostic:
• Refer to Gynecologist
– Saline infusion sonohysterography
• TVUS after infusion of saline into endometrial cavity
• Good for visualizing small lesions
• No tissue obtained
– Hysteroscopy
• Direct visualization → directed biopsy
• Good for small, focal lesions
– MRI
• Good for identifying fibroids, adenomyosis
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References
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Albers JR; Hull SK. Abnormal uterine bleeding. Am Fam Physician. 2004
Apr 15;69(8):1915-26.
Goldstein RB; Bree RL; et al. Evaluation of the woman with
postmenopausal bleeding: Society of Radiologists in UltrasoundSponsored Consensus Conference statement.
J Ultrasound Med. 2001 Oct;20(10):1025-36. Review.
Goodman A. Evaluation and management of uterine bleeding in
postmenopausal women. UpToDate online 2006.
Karlsson B; Granberg S; et al. Transvaginal ultrasonography of the
endometrium in women with postmenopausal bleeding--a Nordic
multicenter study. Am J Obstet Gynecol 1995 May;172(5):1488-94.
Dijkhuizen FP; Brolmann HA; et al. The accuracy of transvaginal
ultrasonography in the diagnosis of endometrial abnormalities. Obstet
Gynecol 1996 Mar;87(3):345-9.
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References
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Martin, KA. The normal menstrual cycle. UptoDate. Mar 3 2004.
Retrieved Sept 2 2006.
http://www.utdol.com/utd/content/topic.do?topicKey=r_endo_f/2305&type
=A&selectedTitle=1~60
Master-Hunter, T and Heiman, DL. Amenorrhea: evaluation and
treatment. Am Fam Physician 2006;73:1374-82.
Beckman, CRB et al. Obstetrics and Gynecology. Lippincott Williams
and Wilkins. New York, NY. 2002.
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