CASE REPORT

SECONDARY AMENORRHEA

Supervised by :
dr. Ismu Setyo Djatmiko, Sp.OG

Presented by :
Ninta Karina Astila Sembiring
2016-061-091

DEPARTMENT OF OBSTETRICS AND GYNECOLOGY

RSUD R. SYAMSUDIN, S.H., SUKABUMI
ATMA JAYA FACULTY OF MEDICINE
2018
 CHAPTER I
INTRODUCTION

Amenorrhea is the absence of menstrual bleeding. In females of reproductive

age, diagnosing amenorrhea is a matter of first determining whether pregnancy is the
etiology. In the absence of pregnancy, the challenge is to determine the exact cause of
absent menses.
Primary amenorrhea is the failure of menses to occur by age 16 years, in the
presence of normal growth and secondary sexual characteristics. If by age 13 menses has
not occurred and the onset of puberty, such as breast development, is absent, a workup
for primary amenorrhea should start.
Secondary amenorrhea is defined as the cessation of menses sometime after
menarche has occurred. Disorders associated with a low or normal FSH, which account
for 66% of cases of secondary amenorrhea, include weight loss/anorexia, nonspecific
hypothalamic, chronic anovulation including PCOS, hypothyroidism, cushing syndrome,
pituitary tumor, empty sella, Sheehan syndrome.
In most cases, clinical variables alone are not adequate to define the
pathophysiologic mechanism disrupting the menstrual cycle. The clinician must be
concerned with an array of potential diseases and disorders involving many organ
systems. However, the history and physical findings help in selecting tests.
Pregnancy is the most common cause of secondary amenorrhea. A pregnancy
test (measurement of serum or urinary human chorionic gonadotropin) is recommended
as a first step in evaluation of a secondary amenorrhea. Thyroid-stimulating hormone
(TSH), prolactin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)
measurements are also the first line of testing.
Treatment is determined by the etiology of the amenorrhea and the desires of the
patient. Ideally, treatment should be directed at correcting the underlying pathology.
 CHAPTER II
CASE REPORT

I. IDENTITY
 Name : Mrs. D
 Age : 21 years old
 Address : Cianjur
 Religion : Moslem
 Marital Status : Married
 Occupation : Housewife
 Date of examination : July, 12th 2018

II. HISTORY
 Chief complaint:
Absence of menstruation since 3 months before came to hospital.

 History of present illness

The patient, 21 years old, P0A0, came to RSUD Syamsudin S.H’s
obstetric and gynecology polyclinic with complaint of absence of
menstruation since 3 months before came to hospital. Patient said that she
had a regular menstrual period before, and her last menstruation was on
April 8th 2018. Patient also got tired easily for last few months. Patient
said that she had a pregnancy test but the results were negative. She
experienced similar complaint 1 year before admission. Then she went to
the obstetric and gynecology polyclinic and was given a drug (she forgot
the name of the drug) then returned to have regular menstruation.

 History of past ilness:

o History of hypertension : Denied
o History of diabetes mellitus : Denied
o History of allergy : Denied
o History of trauma : Denied
 o History of asthma : Denied
o History of surgery : Denied

 Family history:
o History of hypertension : Denied
o History of diabetes mellitus : Denied
o History of asthma : Denied
o History of allergy : Denied

 Medication history :
o No regular drugs is consumed

 Lifestyle:
o Smoking : Denied
o Alcohol : Denied
o Other drugs : Denied

 Contraception History
o Patients never used contraception before.

 History of menstrual cycle:

o Menarche : 12 years old
o Menstrual cycle : regularly every 28-30 days, 7 days
duration and without history of
pain during menstruation
o Amount of menstrual blood : 2-3 normal pads / day ( ± 60 cc )
o Last Menstrual Period : April 8th 2018

 Marital History
Married once, she has been married for 2 years.
  Obstetric history:
No Years Gestatio Helper Labor Sex Complication
nal Age History

Never got pregnant

III. PHYSICAL EXAMINATION

 General condition : mildly ill appearance
 Level of conciousness : compos mentis
 Vital signs:
o Blood pressure : 110/70 mmHg
o Heart rate : 88 beats per minute
o Respiratory rate : 20 breaths per minute
o Body temperature : 36,5 oC
 Height : 155 cm
 Weight : 70 kg
 BMI : 29,16 kg/m2  Obese grade I

General Examination
 Eyes : anemic conjunctiva -/-, icteric sclera -/-
 Nose : deviation -, secrete -/-, deformity -
 Mouth : wet oral mucosal membrane
 Neck : thyroid enlargement -, trachea in in the middle
 Thorax :
o Heart : Regular 1st and 2nd heart sounds, gallop (-),
murmur (-)
o Lung : Vesicular breath sounds +/+, rhonki -/-, wheezing
-/-
o Mammae : hyperpigmentation of areola +/+, nipple retraction
-/-, breast milk -/-
  Abdomen :
o Inspection : convex
o Auscultation : bowel sounds (+), 8 times per minute
o Palpation : supple, mass -
 Extremities : edema (-/-/-/-), CRT <2 seconds, physiologic reflex
(++/++/++/++), pathologic reflex (-/-/-/-)

Gynecologic Examination
 LMP : April 8th 2018
 Inspection : vulvovagina within normal limit, blood -, vaginal
discharge -
 Inspeculo : blood -, erotion -, tissue -, vaginal discharge -
 Vaginal toucher : rugae +, mass-, smooth surface

IV. ULTRASONOGRAPHY (July 12th 2018)

 Uterus : within normal limit

 Adnexa dextra et sinistra : within normal limit
  Ovarium dextra et sinistra : within normal limit

V. WORKING DIAGNOSIS
Mrs. D, P0A0, 21 years-old, secondary amenorrhea

VI. MANAGEMENT
o Outpatient
o Regumen 2x5 mg for 10 days

VII. PROGNOSIS
 Quo ad vitam : bonam
 Quo ad functionam : bonam
 Quo ad sanationam : dubia ad malam
 CHAPTER III
CASE ANALYSIS

Secondary Amenorrhea
Comparison Theory Case

Diagnosis History Taking :  Absence of menstruation 3

 absence or irregular menstrual month before come to the
bleeding hospital
 hypothyroidism
 Lethargy
o lethargy
o weight gain  BMI: 29,16 kg/m2  obesity
o cold intolerance grade 1
 hyperprolactinemia
 BhCG urine : negative
o nipple discharge, usually
bilateral  Vulva inspection : within
 hyperandrogenism normal limits
o hirsutism
 Inspeculo : within normal
o acne
o virilism limits
 history of dilation and curettage  VT : within normal limits
(D&C), myomectomy, cesarean
 USG : uterus, adnexa, and
delivery, or endometritis
ovarium within normal limits
Physical Examination
 Low or high BMI
 Galactorrhea
 Hirsutism appearance

Additional Examination:
 BhCG urine : negative
 TSH and prolactine levels
 Ultrasonography : vary based on
etiologies
Management  Progesterone Challenge Test:  Progesterone Challenge Test:
o Oral medroxyprogesterone o Norethisterone 2x 5 mg PO
acetate for 5-10mg daily for 7- for 10 days
10 days
 Positive: withdrawal
bleeding 2-7 days after
 Estrogen-Progesterone Challenge
Test:
o Oral conjugated estrogen
(1.25mg) or 2 mg estradiol for
days 1 through 21 with oral
medroxyprogesterone acetate
10 mg on days 17 through 21
 Positive: withdrawal
bleeding 2-7 days after
 CHAPTER IV
LITERATURE REVIEW

1. DEFINITION
Secondary amenorrhea is defined as the cessation of regular menses for three
months or the cessation of irregular menses for six months.
The absence of menstrual bleeding in a woman who had been menstruating but
later stops menstruating for three or more months.

2. ETIOLOGY
o Anatomic Abnormalities
o The common anatomic causes of secondary amenorrhea are Asherman
syndrome and cervical stenosis. Asherman syndrome is the presence of
intrauterine synechiae or adhesions, usually secondary to intrauterine
surgery or infection. The potential etiologies of Asherman syndrome
include dilation and curettage (D&C), myomectomy, cesarean delivery,
or endometritis. Cervical stenosis can manifest as secondary amenorrhea
and dysmenorrhea. It is usually caused by scarring of the cervical os
secondary to surgical or obstetric trauma.
o Ovarian Failure
o Ovarian failure may result from ovarian torsion, surgery, infection,
radiation, or chemotherapy. Premature ovarian failure (POF) is often
idiopathic. Any time menopause occurs without another etiology before
age 40, it is considered POF. Before age 35, chromosomal analysis is
usually performed to diagnose a genetic basis for POF. Patients with
either idiopathic POF or a known cause of early ovarian failure are
generally treated with supplemental estrogen to decrease the risk of
cardiovascular disease and osteoporosis.
o Polycyctic Ovarian Syndrome
o Polycystic Ovary Syndrome (PCOS), also known as Stein-Leventhal
syndrome. However, it is now known as one of the most common
 hormonal disorders in women, and has a prevalence of 5% to 10% in the
United States and developed world. Diagnosis is made when women meet
two of three of the following: oligo or anovulation, clinical or laboratory
evidence of hyperandrogenism, and polycystic ovaries on ultrasound.
Clinical evidence of hyperandrogenism may include excessive hair
growth (hirsutism) and male pattern hair loss as well as acne.
o Many patients with PCOS who are hyperandrogenic and obese also
develop insulin resistance and hyperinsulinemia.
o Treatment of these patients depends on the particular symptoms and the
desires of the patient. For patients desiring pregnancy, ovulation
induction may be performed using clomiphene citrate (Clomid). Patients
with PCOS may be particularly resistant to ovulation induction, even with
medication. Further, there is evidence that the probability of ovulation
can be significantly increased by weight loss; therefore, patients are
strongly encouraged to take an active role in maintaining or losing weight
prior to pregnancy. In patients with hyperinsulinemia and insulin
resistance, metformin may increase spontaneous ovulation.
o For patients who are not currently interested in fertility, the goal of
therapy is menstrual cycle control. Oral contraceptive pills not only will
assist in cycle regulation and reduce risk of endometrial hyperplasia or
carcinoma, but also may improve symptoms of acne and arrest further
development of hirsutism by decreasing circulating levels of androgens.
If estrogen is contraindicated, or patient preference indicates, progestin
therapy alone in the form of a levonorgestrel IUD, oral pills (Provera), or
injectable medications (Depo-Provera) will similarly decrease their risk
of endometrial disease. Most clinicians would recommend that patients
undergo a screen for type 2 diabetes mellitus.
o Hyperprolactinemia-Associated Amenorrhea
o Excess prolactin leads to amenorrhea and galactorrhea. Menstrual
irregularities often result from abnormal gonadotropin (FSH and LH)
secretion due to alterations in dopamine levels typically seen in
 hyperprolactinemia.
o Prolactin release is inhibited by dopamine and stimulated by serotonin
and thyrotropin-releasing hormone (TRH). Because of the constant
suppression of prolactin release by hypothalamic release of dopamine,
any disturbance in this process by a hypothalamic or pituitary lesion can
lead to disinhibition of prolactin secretion.
o Hyperprolactinemia has several possible etiologies. Primary
hypothyroidism that leads to elevated thyroid-stimulating hormone (TSH)
and TRH can cause hyperprolactinemia. Medications that increase
prolactin levels (by a hypothalamic–pituitary effect) include dopamine
antagonists (Haldol, Reglan, phenothiazine), tricyclic antidepressants,
estrogen, monoamine oxidase (MAO) inhibitors, and opiates. A prolactin-
secreting pituitary adenoma leads to elevated prolactin levels. The empty
sella syndrome, in which the subarachnoid membrane herniates into the
sella turcica, causing it to enlarge and flatten, is another cause of
hyperprolactinemia.
o Disruption of The Hypothalamic-Pituitary Axis
o As in the hypothalamic and pituitary causes of primary amenorrhea,
disruption in the secretion and transport of GnRH, absence of pulsatility
of GnRH, or acquired pituitary lesions will all cause hypogonadotropic
hypogonadism. Common causes of hypothalamic dysfunction include
stress, exercise, anorexia nervosa, and weight loss.

3. DIAGNOSIS

The approach to secondary amenorrhea always begins with a beta human

chorionic gonadotropin (β-hCG) assay to rule out pregnancy often before a formal
history is taken. If this is negative, the standard history should include focused questions
toward hypothyroidism (e.g., lethargy, weight gain, cold intolerance),
hyperprolactinemia (e.g., nipple discharge, usually bilateral), and hyperandrogenism
(e.g., recent changes in hirsutism, acne, or virilism). TSH and prolactin levels should
then be checked to rule out hypothyroidism and hyperprolactinemia, both of which can
cause amenorrhea. If both are elevated, the hypothyroidism should be treated and the
prolactin level can be checked after thyroid studies have normalized to verify resolution.
If the prolactin level is elevated and TSH is normal, a workup for the other
causes of prolactinemia should ensue. In the diagnostic evaluation of the patient, a
careful history should be taken, including a complete list of medications and clear
documentation of the onset of symptoms. A thorough physical examination should
include visual fields, cranial nerves, breast examination, and an attempt to express milk
from the nipple. An MRI can rule out a hypothalamic or pituitary lesion.
If the prolactin level is normal, a progesterone challenge test (10 mg orally for
7 to 10 days to mimic progesterone withdrawal) can be performed to assess the
adequacy of endogenous estrogen production and the outflow tract. Withdrawal bleeding
occurring after the progesterone challenge indicates the presence of estrogen and an
adequate outflow tract. In this case, amenorrhea is usually secondary to anovulation,
which can be caused by a variety of endocrine disorders that alter pituitary/gonadal
feedback such as polycystic ovaries, tumors of the ovary and adrenals, Cushing
syndrome, thyroid disorders, and adult-onset adrenal hyperplasia.
Absence of withdrawal bleeding in response to progesterone alone must then be
evaluated with estrogen and progesterone administration. If there is still no menstrual
bleeding, an outflow tract disorder such as Asherman syndrome or cervical stenosis is
suspected. If menstrual bleeding does occur in response to estrogen and progesterone
administration, this suggests an intact and functional uterus without adequate
endogenous estrogen stimulation. Measurement of FSH and LH will help differentiate
between a hypothalamic–pituitary disorder (low/normal FSH and LH levels) and ovarian
failure (high FSH and LH levels).
Guidelines for Progestogen and Estrogen/Progestogen Challenge Tests
Drug Dosing Duration

Progestogen challenge test

Medroxyprogesterone acetate 10 mg orally once per day Seven to 10
(Provera) days
Norethindrone (Aygestin) 5 mg orally once per day Seven to 10
days
Progesterone 200 mg parenterally once per Single dose
day
Progesterone micronized 400 mg orally once per day Seven to 10
days
Progesterone micronized gel (4 or Intravaginally every other Six
8%) day applications
 Drug Dosing Duration

Estrogen/progestogen challenge test

Conjugated equine estrogen 1.25 mg orally once per day 21 days
(Premarin)
or
Estradiol (Estrace) 2 mg orally once per day 21 days
followed by
Progestational agent As noted above As noted above

4. TREATMENT
Patients with hypothyroidism are treated with thyroid hormone replacement.
Those with pituitary macroadenomas are treated with surgical resection. Some patients
with macroadenomas and most with microadenomas are treated with bromocriptine, a
dopamine agonist that often causes tumor regression and the resumption of ovulation.
Other hyperprolactinemic patients can also be treated with bromocriptine in order to
resume ovulation. Further, this treatment should be followed with serial prolactin levels
and cone view radiographs to diagnose development of a macroadenoma.
Patients who respond to a progesterone challenge should be withdrawn with
progesterone on a regular basis to prevent endometrial hyperplasia. Oral contraceptive
pills (OCPs) are useful in this case and may be beneficial in the management of
hirsutism. For patients who are hypoestrogenic, consideration should be given to
estrogen and progesterone replacement for the effects these have on bone density and
genital atrophy.
 REFERENCE

1. Hoffman, et al. Williams Gynecology. 3rd edition. New York: Mc. Graw Hill. 2016.
2. Tamara Callahan, Aaron B. Caughey. Blueprints Obstetrics and Gynecology. 6th edition.
2013
3. Amenorrhea: An Approach to Diagnosis and Management - - American Family
Physician [Internet]. Available from: https://www.aafp.org/afp/2013/0601/p781.html
4. Amenorrhea: Background, Pathophysiology, Etiology. 2018 May 24; Available from:
https://emedicine.medscape.com/article/252928-overview