The classification of secondary amenorrheas

The classification of secondary amenorrheas

 Secondary Amenorrhea

Secondary amenorrhea is defined as the absence of menses for 6 months in a female who has had previous normal menstrual function.


The classification of secondary amenorrheas appears in Box 1.

  1. Functional ovaries.
  2. Asherman’s syndrome
    1. Asherman’s syndrome is the result of intrauterine synechiae, usually after curettage in association with endometritis (incom­plete abortion or postpartum hemorrhage), but may occur with any operative procedure involving the uterine canal (myo­mectomy, septum resection, etc.).
    2. Diagnosis is made by hysteroscopy or, less reliably, by hysterosalpingogram.
    3. Asherman’s syndrome is divided into grades (grade 1, mucosal adhesions, to grade 4, uterine cavity obliteration), which reflect on surgical correctability and subsequent pregnancy rate.
    4. Degree of menstrual flow or Provera withdrawal bleeding depends on amount of functional endometrium.
    5. Treatment consists of hysteroscopically directed lysis of adhe­sions with 90% probability of menstrual return and 35% to 50% pregnancy rate.
  3. Endometrial destruction
    1. By radiation or by infectious organisms (tuberculosis and schistosomiasis).
    2. Uterine cavity may be maintained but is replaced by nonfunc­tional epithelium.
    3. Hypergonadotrophic amenorrhea.
      • FSH and LH are increased and estrogen levels are low.
      • Ten percent of secondary amenorrheas are caused by premature ovarian failure (menopause before age 40).
      • It is associated with autoimmune disease, especially hypothyroidism.
      • Antiovarian antibodies are present in 30% to 50%.
      • Other causes include radiotherapy, chemotherapy (especially alky­lating agents), chromosomal abnormalities, galactosemia, and post- adnexal surgery.

Reports of spontaneous remission and pregnancy are found in the literature, but the condition is usually irreversible.


BOX 1. The Classification of Secondary Amenorrheas
Functional Ovaries
 Asherman’s syndrome
 Endometrial destruction
 Premature ovarian failure
 Iatrogenic ovarian failure
Hypothalamic—pituitary dysfunction
Eating disorders
Exercise induced
Central nervous system lesions
Nongonadal endocrinopathy
Acute and chronic disease
 Central nervous system disease
 Feminizing ovarian tumors
Androgen Excess
 Polycystic ovarian disease
Masculinizing ovarian tumors



  1. In vitro pregnancy with donor eggs or zygotes is an option for those requesting pregnancy.
  2. Eugonadotrophic amenorrhea.
    • The majority of patients with secondary amenorrhea have eugona­dotrophic amenorrhea.
    • Hypothalamic—pituitary dysfunction is the most common cause but is a diagnosis of exclusion.
    • Mechanism is likely a slowing of the hypothalamic gonadotropin- releasing hormone (GnRH) pulse generator with increased CRF (corticotropin), growth hormone, and nocturnal melatonin.
    • There is a blunted response to GnRH stimulation.

Prognosis is usually good if the underlying cause is treatable. (1) Psychogenic amenorrhea.

  • Increased CRF leads to decreased GnRH and therefore decreased LH.
  • The cause may be acute or chronic stress.
  • Treatment includes the following:
    • Stress management
    • Antidepressants
    • Psychopharmaceutical
    • Estrogen replacement
    • If necessary, ovulation induction
      • Weight loss—induced amenorrhea.
        • A minimum of 17% body fat is required for menarche.
        • Menstrual maintenance requires 22% body fat, but body fat is not the only determinant.
        • Anorexia nervosa is an extreme example and is associated with increased conversion of estradiol to catecholestrogens, which suppresses the hypothalamus.
        • Treatment includes the following:

(i) Dietary counseling fii) Behavior modification

  • Estrogen replacement
  • Ovulation induction (should be carried out only after careful consideration of underlying pathology)
  • Exercise-induced amenorrhea.
  • A combination of stress, weight loss, loss of body fat, and dietary control causes* this: If
  • Individuals’ responses of CRF axis exercise intensity are important variables.
  • No consistent relationship to endogenous opiates exists.
  • Bone loss has been documented in amenorrheic athletes.
  • Treatment includes the following:
    • Decreasing exercise
    • Increasing body fat
    • Estrogen replacement
    • Pregnancy counseling (should be carried out before ovulation induction)
        • All the symptoms and many of the signs of pregnancy are present.
        • Increased pulses of LH and prolactin with normal FSH are seen.
        • The LH/FSH ratio is high (> 2).
        • Treatment includes counseling and ovulation induction.
      • Postpill amenorrhea.
        • Hypothalamic oversuppression syndrome.
        • Postpill amenorrhea occurs in less than 1% of women on the birth control pill (BCP).
        • There is no relationship to dose or duration of BCP use.
        • Spontaneous recovery may take years.

Treatment includes ovulation induction or sequential cyclic hormonal replacement.

  • Central nervous system (CNS) lesions.
    • These are most often pituitary or parapituitary lesions.
    • Amenorrhea with galactorrhea is a common presentation, but hyperprolactinemia can occur without galactorrhea.
    • Hyperprolactinemia requires a search for a pituitary micro­adenoma, especially with amenorrhea.
    • Pituitary gummas, nonfunctional pituitary tumors, postpar­tum ischemia (Sheehan’s syndrome), and internal carotid aneurysms can cause pituitary insufficiency and present as amenorrhea.
    • Destructive lesions of the hypothalamus usually have neu­rologic symptoms preceding the amenorrhea.
    • Treatment requires an accurate diagnosis.

(i) Parlodel is the treatment of choice for prolactin-pro- ducing pituitary microadenomas.

  • Radiation or surgery is used for macroadenomas or other microadenomas.
  • Parlodel use has been shown to shrink the size of pituitary adenomas.
    • Amenorrhea with other endocrinopathies.
      • Thyroid dysfunction (usually hyperthyroidism) often pre­sents with amenorrhea.
      • Juvenile diabetes mellitus and adrenocortical dysfunction may also cause amenorrhea.
    • Drug-induced amenorrhea.
      • Dopamine antagonists (phenothiazines, metoclopramide, etc.) can cause amenorrhea by elevation of prolactin.
      • Cytotoxic agents, especially alkylating agents, can cause ovar­ian follicular destruction that is often irreversible. Increased duration of therapy and patient age worsen prognosis.
      • Depo-Provera has been associated with prolonged amenorrhea.
      • Drug addiction has also been associated with amenorrhea.
    • Chronic and acute disease: Often caused by nutritional or stress factors, but a variety of metabolic pathways may also be involved. Correction of the underlying disease often results in return of menses.

(10) Estrogen-producing tumors: These tumors are rare but should be considered if endometrial hyperplasia is noted.

  1. Amenorrhea with androgenic excess: The source of androgen may be ovarian or adrenal, a. Polycystic ovarian disease
  • This is the main cause of ovarian hyperandrogenic state.
  • Results from altered feedback at hypothalamic level resulting in excessive suppression of FSH. Higher LH levels result in increased androgen production by theca cell layer in develop­ing follicles.


Oligomenorrhea, obesity, hirsutism, and infertility are often present.


  1. Ovaries often have the characteristic smooth, thick, white capsule with multiple small developing follicles. This appear­ance can also be detected by ultrasound.
  2. Increased LH/FSH ratio (> 2), increased androstenedione, and free testosterone are present.
  3. Treatment involves the following:
    1. Cyclic progesterone (protection against endometrial hyperplasia)
    2. Birth control pills (endometrial protection, suppression of ovarian androgenic production, and increased sex hor­mone—binding globulin)
    3. Ovulation induction
      • Late-onset congenital hyperplasia
        • It presents with hirsutism and dysfunctional uterine bleeding.
        • Increased frequency is seen in Eastern European Jews and Hispanics.
        • Diagnosis is made by adrenocorticotropic hormone (ACTH) stimulation test.
        • Treatment requires replacement therapy with prednisone or dexamethasone.

Masculinizing ovarian tumors usually have high androgen levels.












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