Amenorrhea

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Primary Amenorrhea Definition

-Absence of menarche by the age of 16

Secondary Amenorrhea Definition

-absence of menses for more than three cycle intervals or six months in women who were previously menstruating

Causes of Primary Amenorrhea (7)

1) Chromosomal abnormalities — 45%
2) Physiologic delay of puberty — 20%
3) Müllerian agenesis — 15%
4) Transverse vaginal septum or imperforate hymen — 5%
5) Absent hypothalamic production of GnRH - 5%
6) Anorexia nervosa — 2%
7) Hypopituitarism — 2%

Diagnostic Evaluation for Primary Amenorrhea (5)

1) Normal pubertal development?
2) Was pt's neonatal/childhood health normal?
3) Family history of delayed/absent menarche?
4) Any symptoms of virilization?
5) Any galactorrhea? (hyperprolactinemia)

More History Questions

1) Any recent increase in stress, or change in weight, diet, or exercise habits?
2) Is pt taking any meds or drugs?
3) Short stature compared to family members?
4)Hypothalamic-pituitary disease (headaches, visual field defects, fatigue, polyuria or polydipsia?)

Drugs Associated with Amenorrhea: Drugs that Increase Prolactin

1) antipsychotics
2) Tricyclic Antidepressants
3) Calcium channel blockers

Drugs Associated with Amenorrhea: Drugs with Estrogenic activity

1) digoxin
2) marijuana
3) OCPs

Drugs Associated with Amenorrhea: Drugs with Ovarian Toxicity

1) Chemotherapeutic agents

Physical Exam (4)

1) Evaluation of pubertal development - including height, weight, & Tanner staging.

2) Pelvic exam to check for presence of cervix, uterus, ovaries (may need ultrasound)

3) Check skin for signs of androgen excess (acanthosis nigricans, hirsutism, acne, & striae) and vitiligo (thyroid disorders)

4) Check for physical features of Turner syndrome (low hair line, web neck, shield chest, and widely spaced nipples)

Tanner Staging

Stage 1) Prepubertal
Stage 2) Breast bud stage with elevation of breast and papilla, enlargement of areola
Stage 3) Further enlargement of breast and areola, no separation of their contour
Stage 4) areola and papilla form a secondary mound above level of the breast
Stage 5) mature stage with projection of papilla only; related to recession of areola

If uterus not found on exam (2)

1) If normal vagina or uterus not obviously present on PE, a pelvic U/S is performed to confirm the presence or absence of ovaries, uterus, and cervix.

2) If no uterus found, further evaluation should include a karyotype and measurement of serum testosterone.

Endocrine exams if patient does have a uterus

1) Check serum B-HCG, FSH, TSH, & prolactin.
-If signs or symptoms of hyperandrogenism, serum
testosterone & DHEA-S should be measured to assess
for an androgen-secreting tumor.

Correcting the underlying pathology: Congenital anatomic lesions

Corrective surgery

Correcting the underlying pathology: Y chromosome

1) Gonadectomy to prevent the development of gonadal neoplasia.

2) Delayed until after puberty in patients with complete androgen insensitivity syndrome.

PCOS

1) MC hormonal disorder among women of reproductive age.
2) Signs and symptoms vary from person to person, in both type and severity.

Polycystic Ovaries

1) Enlarged ovaries containing numerous small cysts - ultrasound.
2) To be diagnosed with PCOS, you must also have abnormal menstrual cycles or signs of androgen excess.
3) Some women with polycystic ovaries may not have PCOS, while a few women with the condition have ovaries that appear normal

PCOS: Menstrual abnormality.

1) Most common characteristic.
-Examples: menstrual intervals longer than 35 days;
fewer than eight menstrual cycles a year; failure to
menstruate for four months or longer; and prolonged
periods that may be scant or heavy.

PCOS: Excess androgen

1) Hirsutism
2) Adult acne or severe adolescent acne
3) Androgenic alopecia

Other conditions associated with PCOS : Infertility

1) Infrequent ovulation or a lack of ovulation.
2) PCOS is the most common cause of female infertility.

Other conditions associated with PCOS : Obesity

-About half the women with polycystic ovary syndrome are obese compared with women of a similar age who don't have polycystic ovary syndrome

Other conditions associated with PCOS : Prediabetes or Type II DM

1) Insulin resistant, which impairs the body's ability to use insulin effectively to regulate blood sugar. This can result in high blood sugar and type 2 diabetes.

Other conditions associated with PCOS : Acanthosis nigricans

1) This skin condition may be a sign of insulin resistance.

Treatment of PCOS: Hirsutism

1) Electrolysis or laser treatment.

2) Slowing of hair growth by administration of an oral contraceptive alone or in combination with an antiandrogen (eg: Sprironolactone)

Treatment of PCOS: Endometrial Protection

OCPs

Treatment of PCOS: Anovulation and Infertility

Clomiphene , GnRH, Metformin

Secondary Amenorrhea: Causes

1) Pregnancy
2) Ovarian disease — 40%
3) Hypothalamic dysfunction — 35%
4) Pituitary disease — 19%
5) disease — 5%
6) Other — 1%

Causes of Primary and Secondary Amenorrhea: Anatomic (7)

1) pregnancy
2) adhesion (intrauterine)
3) gonadal dysgenesis
4) impeforate hymen
5) vaginal septum
6) cervical stenosis
7) gestational trophoblastic neoplasia

Causes of Primary and Secondary Amenorrhea: ovarian failure

1) menopause
2) surgery, radiation, chemotherapy,
3) chromosomal:
-Turner's Syndrome
-Androgen Insensitivity Syndrome
4) Resistant Ovary Syndrome

Causes of Primary and Secondary Amenorrhea: Endocrine (6)

1) hypothalamic/pituitary tumors
2) hyperprolactenemia
3) isolated gonadotrophin deficiency
4) hyperandrogenism
-PCOS
-ovarian/adrenal tumor
-testosterone injections
5) hypothyrodism
6) Cushing's Disease

Causes of Primary and Secondary Amenorrhea: other

1) stress
2) anorexia
3) post OCP
4) illness
5) exercise

High serum Prolactin: Imaging (3)

1) To rule out a hypothalamic or pituitary tumor.
2) Screen twice before ordering imaging
3) CT is frequently adequate, MRI provides a better view of the hypothalamic-pituitary area

High serum Prolactin: Prolactinoma (1)

1) Microadenoma (<1 cm) Macroadenoma (>1 cm)

High serum Prolactin: Treatment (2)

1) Dopamine agonist (cabergoline, bromocriptine, pergolide)
2) Other options include surgery, radiation therapy and estrogen

Progesterone challenge: Assess estrogen status

1) Medroxyprogesterone acetate (Provera) 10 mg OD for 10 days
-any uterine bleed within 2 - 7 days after completion is considered to be a positive test/withdrawal bleed

Progesterone challenge: withdrawal bleed

-adequate estrogen

Progesterone challenge: no bleeding occurs

-hypoestrogenism

High serum FSH: indications, reasons why, treatment

1) Indicates the presence of ovarian failure.
2) Repeat monthly x 3 to confirm persistent elevation.
3) Ovarian failure due to normal or early menopause

No treatment available for primary ovarian failure, but women should take supplemental calcium and vitamin D.

High serum androgen concentrations: implications

A high serum androgen value may solidify the diagnosis of PCOS, or may raise the question of an androgen-secreting tumor of the ovary or adrenal gland.

High serum androgen concentrations: evaluate for what if values are high?

Initiate evaluation for a tumor if the serum concentration of testosterone is greater than 150 to 200 ng/mL or that of DHEA-S is greater than 700 µg/dL

High serum androgen concentrations: ultrasound to rule out:

U/S to rule out cyst, PCOS

Normal or low serum gonadotropin concentrations and all other tests normal: values, what is indicated, further tests

-Hypothalamic amenorrhea
-One of the most common outcomes of laboratory testing in women with amenorrhea.
-Normal to low FSH values, with FSH typically higher than LH
-Cranial MRI is indicated in all women without a clear explanation for hypogonadotropic hypogonadism
-No further testing is required if the onset of amenorrhea is recent or is easily explained and there are no symptoms suggestive of other disease

Asherman's syndrome

-Formation of interuterine adhesions

-Endometrial scarring and intrauterine adhesions may occur as a result of surgical scraping or cleaning of tissue from the uterine wall (D and C) or infections of the endometrium (e.g., endometritis, tuberculosis)

Asherman's syndrome: testing

-Progestin challenge (Provera 10 mg qD x 10 d)
-If withdrawal bleeding occurs, an outflow tract disorder
has been ruled out.
-If bleeding does not occur, estrogen and progestin should be administered (conjugated estrogen x 35 d with medroxyprogesterone for last 10 d)
-Failure to bleed upon cessation of this therapy strongly suggests endometrial scarring.
-Hysterosalpingogram or direct visualization of the endometrial cavity with a hysteroscope for confirmation

Asherman's Syndrome: Treatment

-Therapy consists of hysteroscopic lysis of adhesions followed by long-term estrogen administration to stimulate regrowth of endometrial tissue

Treatment for functional hypothalamic amenorrhea: athletic women

-adequate caloric intake to match energy expenditure is often followed by resumption of menses (70-80%)
-All women athletes with amenorrhea should be encouraged to take 1200 to 1500 mg of calcium daily and supplemental vitamin D (400 IU daily)

Treatment for functional hypothalamic amenorrhea: Nonathletic women who are underweight or who appear to have nutritional deficiencies

-should have nutritional counseling
-Can be referred to a multidisciplinary team specializing in the assessment and treatment of individuals with eating disorders.

Diagnosis: Hypothalamic Amenorrhea

-Etiology is most likely inadequate caloric and fat intake.
-Patient should be referred for evaluation for an eating disorder.
-Chances of normal menstruation are very good if patient takes in adequate calories.

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