Dr. Dianalyn Sazon-Carlos | 08.09.

2016 | Gynecology
AMENORRHEA AND HYPERPROLACTINEMIA

Group II: Associated with evidence of estrogen

AMENORRHEA
production
Absence or abnormal cessation of menses o Normal or Low FSH levels
Primary and secondary amenorrhea Group III: Elevated serum FSH level indicating
describe the occurrence before and after gonadal failure
menarche, respectively.
Primary amenorrhea means that the patient SUGGESTED FLOW DIAGRAM IN THE EVALUATION OF
never had any menses WOMEN WITH AMENORRHEA
Secondary amenorrhea means that the
patient had menses before
Timing of evaluation according to American
Society of Reproductive Medicine (ASRM)
o Failure to menstruate by age 15 in the
presence of normal secondary sexual
development
o Within five years after breast
development if that occurs before age
10
o Failure to initiate breast development by
age 13 because it is the first one to
develop
o In women with regular cycles, a delay of
menses for as little as one week (exclude
pregnancy). The most common cause
of amenorrhea is pregnancy.
o We have to evaluate immediately Rule out pregnancy first before doing
because the patient might be having an
ancillary tests, even if your patient claims to not be
ectopic pregnancy. Advise the patient
pregnant.
to come back to the clinic if she
After ruling out pregnancy, check the FSH
experiences any bleeding or pain just so
we can capture the ectopic pregnancy levels. If FSH levels are elevated, ask for imaging
before it ruptures. studies because it could be a Prolactinoma.
o Secondary amenorrhea lasting 3 months Increased FSH could also be due to Ovarian Failure,
these may even be seen in pre-menopausal
Causes of Primary Amenorrhea patients.
Prevalence: 3-4% Decreased FSH could be due to Chronic
Majority of causes are due to: Anovulation.
o Polycystic Ovary Syndrome Most common causes for normal levels of
Common in obese patients FSH are Anatomic Defects such as you Mullerian
o Hypothalamic Amenorrhea Abnormalities.
o Hyperprolactinemia
o Ovarian Failure CATEGORIZATION OF PHENOTYPES OF INDIVIDUALS
WITH PRIMARY AMENORRHEA
Causes of Amenorrhea (World Health Organization)
Group Breast Uterus
Group I: No evidence of endogenous I Absent Present
estrogen production II Present Absent
o Normal or Low FSH levels
III Absent Absent
o Normal prolactin levels
IV Present Present
o No evidence of a lesion in the
hypothalamic-pituitary region Group IV, also those belonging to Secondary
Amenorrhea, the breast and uterus are both
present.

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 GROUP I: BREASTS ABSENT, UTERUS PRESENT CNS tumors, e.g. craniopharyngioma, pituitary
adenoma
Anatomic Site Gonadotropins
Hypothalamic-pituitary Low or Normal BP MEASUREMENT IN THE DIAGNOSIS OF GROUP I
Ovary Elevated PRIMARY AMENORRHEA

Ovarian - peripheral

Serum FSH Measurement in Diagnosis of Group I

Primary Amenorrhea

Serum FSH level

Low or Normal Elevated

o HYPOGONADOTROPIC,
Hypogonadotropic Hypergonadotropic
HYPOGONADISM- If low or normal FSH
hypogonadism
o HYPERGONADOTROPIC,
hypogonadism
Elevated serum FSH - HYPERGONADOTROPIC
HYPOGONADISM- FSH are elevated HYPOGONADISM

CT or MRI in Diagnosis of Group I Primary HYPERGONADOTROPHIC HYPOGONADISM

Amenorrhea
Gonadal dysgenesis (Turners syndrome, 45 X);
mosaicism
Enzyme deficiency
Irradiation, infections or infiltrative ovarian
disease of ovaries
Chemotherapeutic agents e.g.
cyclophosphamide
Autoimmune ovarian failure
Galactosemia
Resistant ovary syndrome (Savage syndrome)

Group I: Breast Absent, Uterus Present (CAUSES)

TURNER SYNDROME

HYPOGONADOTROPIC HYPOGONADISM
Physiologic or constitutional delay of puberty
Malnutrition e.g. obesity, anorexia nervosa
Stress, excessive exercise
o Rio Olympics winner, most probably she
doesnt have regular menses
Chronic diseases, neoplasia
Marijuana use
Kallmans syndrome

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 Short stature Androgen insensitivity syndrome (testicular
Webbed neck feminization)
Low set hairline &ears
No 20 sex characteristics When dealing with group II primary
Wide spaced nipples amenorrhea, there can be XX or XY. So if it is an XX,
Edema of the feet & hands there is just a congenital absence of the uterus.
Broad shield-like chest There are ovaries and ovulation is present; however,
Pigmented nevi vaginal is very small or just a small pouch vaginal
CVS canal.
o coarctation of the aorta
o MVP If there is androgen insensitivity syndrome,
o aortic aneursyms there is one XY. The gonads are for male. There are
o bicuspid aortic valve few pubic hair, testosterone is high, there is no
Renal: horseshoe kidney ovulation, and more or less external genitalia.
unilateral pelvic kidney
Check for other problems aside from these
characteristics Variations in Clinical and Laboratory Parameters in
Woman with Group II Primary Amenorrhea
TREATMENT OF PATIENTS WITH TURNER SYNDROME
PARAMETER CONGENITAL ANDROGEN-
Continuous daily low-dose androgen ABSENCE OF INSENSITIVITY
THE UTERUS SYNDROME
Gonad Ovary Testes
cessation of linear growth Karyotype 46, XX 46, XY
Pubic Hair Present Absent, Sparse
Testosterone Female range Male range
Estrogen on days 1 - 25 of each month Weekly Ovulation No ovulation
Progestin on days 14 - 25 of each month progesterone
level
Vagina Present, small Present, small
pouch, or pouch, or
absent absent

Group III Primary Amenorrhea (Breast and Uterus

Absent)
EVALUATION

In group III, where there is absence of breast

GROUP II: BREAST PRESENT, UTERUS ABSENT
Congenital absence of uterus
Absence of the vagina with
absence of the uterus is referred to
as Mayer-Rokintansky-Kuster-Hauser
syndrome
and uterus, when the karyotype is XY, think of an
enzyme deficiency or agonadism (vanishing testes
syndrome)
17,20 desmolase deficiency
17 hydroxylase deficiency with 46, XY
karyotype
Agonadism

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 of the cortisol, estrone, and estradiol. In addition,
patient may have hypertension because all
intermediate products prior to blockade of the
enzyme will be shifted to mineralocorticoid
pathway.

Management:
Corticosteroid replacement
Hormone replacement

(Disclaimer: Not the actual photo)

If 17 a-hydroxylase deficiency is confirmed

MANAGEMENT

Corticosteroid replacement with ESTROGEN and

PROGESTIN

GROUP IV PRIMARY AMENORRHEA (BREAST AND

UTERUS PRESENT)
Easiest
Hypothalamic
This is what happens when there is Pituitary
deficiency of 17,20 desmolase enzyme. There will Ovary
be no production of 5 hydroxyprogesterone, 1 Uterine
androstenedione, and estrone. Also there will be
no production of 5 androstenediol, testosterone,
and estradiol; hence, there will be no production of
secondary sexual characteristics. If 17-hydroxylase
is the one deficient, there will be no production

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Diagnostics are similar to those of secondary THERAPEUTIC OBJECTIVES IN HYPERPROLACTINEMIA
amenorrhea since it is normal. Control of galactorrhea
Endocrine Assays Used in the Correction of hypogonadism
Initial Evaluation
Reduction or removal of tumor mass
Estradiol
FSH Management: Bromocriptine, Cabergoline
Prolactin or Quinagolide
TSH Clinical criteria: Menstruation / ovulation
Similar to the evaluation of secondary amenorrhea Biochemical criteria: Serum prolactin value
within normal range after 6-20 weeks of
Causes of Secondary Amenorrhea in One Series treatment
Functional hypothalamic amenorrhea 34
Hyperandrogenism and PCOS 29 Evaluation of Patients with Group IV Primary
Hyperprolactinemia 13 Amenorrhea and Elevated TSH Levels
Premature Ovarian failure 12
Estradiol, FSH, TSH, prolactin
Ashermans syndrome 5
Others 7

Asherman syndrome - there is adhesion, there is TSH elevated

fibrosis in the uterus; your uterus is not capable of
bleeding anymore. Thyroid disorder
Complication of surgery
Frequent dilation and curettage causing
trauma. If TSH is elevated, just concentrate on
thyroid disorders.
Evaluation of Patients with Group IV Primary If Estradiol is elevated, do imaging studies.
Amenorrhea and Hyperprolactinemia
Evaluation of Patients with Group IV Primary
Estradiol, FSH, TSH, prolactin
Amenorrhea and Serum Estradiol Levels >40
pg/ml
Prolactin elevated Do imaging studies

Estradiol, FSH, TSH, prolactin

Hyperprolactinemia
evaluation Estradiol >40 pg/ml

CAUSES OF HYPERPROLACTINEMIA Pelvic sonography

Most common:
o Prolactin-secreting pituitary adenoma >12 follicles 8-9 mm Normal ovaries
(>=20 ng/ml,1/3 will have amenorrhea, in size per ovary
1/3 will have galactorrhea) Hypothalamic-
Less frequent causes: drugs, primary pituitary dysfunction
hypothyrodism
PCOS
Related to PCOS, adrenal, renal or hepatic
diseases Amenorrhea and Serum Estradiol Levels <40
Idiopathic: Prolactin elevated, no pg/ml
demonstrable pituitary/ hypothalamic
lesions/ other causes

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 Estradiol, FSH, TSH,
prolactin levels

Estradiol <40 pg/ml

FSH normal or low FSH high (> 30 mIU/ml)

Hypothalamic- pituitary Premature ovarian

failure failure

TSH, FBS, Ca, P <25 y of <35 y of age

MRI or CT scan of CNS age
ACTH reserve test (unless
history of drug ingestion, Karyotype
severe stress, strenuous
exercise, or marked <35 y age
weight loss) Antinuclear
antibodies
Antihyroid antibodies
Rheumatoid factors
TSH,24-h urine-free
cortisol
Management of Primary Amenorrhea

Treatment of Primary Amenorrhea

with Breast and Uterus Present

If the patient wants to conceive and she has high

estrogen level, you can give CLOMID and fertility
drugs.

If it is <40pg/ml:

o Low FSH, you can give injectable,

gonadotrophins
o High FSH (more likely in menopause or
ovarian failure),you just have to offer
donor eggs.

If pregnancy not desired, just give hormones, either

progesterone or pills.

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