Amenorrhea (No Periods)

Last updated On August 26th, 2021

Definition –

1 No menses by age 14 years and no other evidence of pubertal development.
2 no menses by age 16 despite the presence of other pubertal signs.
3 previous menstrual cycles but now without menses for a time equivalent to three cycles or 6 months.
• Physiologic amenorrhea is seen in prepubescent girls, during pregnancy and lactation (breastfeeding), and after menopause.
• Pathologic (non-physiologic) amenorrhea occurs in 3–4% of reproductive age women and should be investigated to determine the underlying etiology.

Due to significant overlap, prior categorization of amenorrhea as primary or secondary should be avoided. Proper evaluation requires a systematic approach to making a correct diagnosis.

Anatomic disorders

Inherited

Frequent cause in adolescents:
1 Müllerian agenesis (Mayer–Rokitansky–Küster–Hauser syndrome; 1/5,000 female births) involves the congenital absence of all or part of the uterus and vagina. Treatment: creation of a neovagina by progressive dilation or surgery (McIndoe operation).
2 Imperforate hymen (1/2,000) and transverse vaginal septum (1/70,000 women) are distal outflow tract obstructions.

Treatment:

Hymenectomy/excision.

Acquired

1 Intrauterine synechiae (Asherman syndrome) after vigorous uterine curettage in early pregnancy may lead to scarring that interferes with normal endometrial growth and shedding. Treatment: hysteroscopic lysis of intrauterine adhesions and stimulation of the endometrium with estrogen.

2 Cervical stenosis may result from D&C (dilation and curettage), cone biopsy, or infection. Treatment: dilation of the cervix.

Endocrine disorders

Hypergonadotropic hypogonadism (premature ovarian failure)

• Etiology –

Primary ovarian dysfunction, not due to the hypothalamus or pituitary.

• Definition –

Loss of oocytes before age 40.

• Diagnosis –

Two serum FSH levels >40 mIU/mL, drawn at least 1 month apart.

• Incidence –

This occurs in 1/100 women aged <40.

• Gonadal dysgenesis –

It is characterized by streak gonads (bands of fibrous tissue in place of the ovary). Synthesis of ovarian steroids does not occur due to the absence of ovarian follicles. Breast development does not occur because of the very low circulating estradiol levels. Turner syndrome (45, XO) accounts for >50% of patients. The remaining causes are commonly due to other non-inherited chromosomal disorders or deletions.

• Treatment –

Hormone replacement therapy to develop breast tissue and prevent osteoporosis. The presence of a Y chromosome on karyotype requires excision of gonadal tissue to prevent the 25% incidence of malignancy.

• Acquired abnormalities –

It includes autoimmune processes (eg, myasthenia gravis), chemotherapy, radiation, or infection. Treatment: None, but hormone replacement therapy should be considered.

Hypogonadotropic hypogonadism

• Etiology –

Primary hypothalamic-pituitary dysfunction.

• Definition –

A decrease in gonadotropin stimulation of the ovaries leads to loss of ovarian follicle development and results in very low estrogen levels.

1 Hypothalamic disorders

• Inherited hypothalamic disorders are idiopathic. Kallman syndrome is one variant often associated with the inability to smell and other z facial anomalies. Treatment: hormone replacement therapy.
• Acquired hypothalamic dysfunction may be due to brain tumors, physical or emotional stress, weight loss, exercise, or pseudocyesis (the ability of the mind to control physiologic processes).

Treatment –

Unless a tumor is present, behavioral modification or hormone replacement therapy may be appropriate, or therapy may be unnecessary if the underlying cause of the amenorrhea is not threatening to her health.

2 Pituitary disorders

Inherited pituitary disorders may result in hypoplasia.

Treatment –

Hormone replacement therapy.

• Acquired pituitary dysfunction –

It is most commonly due to a prolactin-secreting adenoma, but metastatic tumors or Sheehan syndrome (panhypopituitarism resulting from massive postpartum hemorrhage, pituitary ischemia, and necrosis) is also possible.

Treatment –

Surgical resection is usually indicated for patients with pituitary macroadenomas. Other hyperprolactinemic patients should be followed with serial prolactin levels and head imaging to exclude the development of a macroadenoma. Sheehan syndrome is managed with hormone replacement therapy.

3 Chronic Illnesses

Chronic illnesses such as end-stage kidney disease, AIDS, or advanced liver disease can also result in hypogonadotropic amenorrhea. Eugonadotropic hypogonadism

• Etiology –

Disorders that cause amenorrhea, but are not associated with abnormal gonadotropin levels:
1 Polycystic ovarian syndrome (PCOS) 
2 Congenital adrenal hyperplasia (CAH; adult-onset) resembles PCOS clinically but is usually due to a gene mutation resulting in patients shunting progesterone precursors to the androgen pathway.
Treatment: hormone replacement therapy.

3 Hyperprolactinemia and hypothyroidism.

Infertility –

• As many of the diagnoses are made during childhood or adolescence, counseling is very important. Insensitivity can be very psychologically devastating to a girl who is told that she does not have a uterus, is genotypically male, or is permanently infertile.
• Fortunately, anatomic disorders can usually be corrected to provide an appropriate functional result.
• Hypergonadotropic patients may be able to conceive using a donor oocyte and in vitro fertilization.
• Hypogonadotropic patients may become fertile with pulsatile GnRH or gonadotropins.
• Eugonadotropic patients, especially those with PCOS, will frequently ovulate with clomiphene citrate