Ovarian Insufficiency Clinical Presentation

Updated: Nov 17, 2016
  • Author: Vincent A Pellegrini, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Presentation

History

Generally, women with spontaneous POI/POF have unremarkable clinical findings.

  • Occasionally, signs of Turner syndrome may be evident (short stature, shieldlike chest, webbed neck, shortened IV and V metacarpal bones, wide carrying angle of elbows, low-set ears and low hairline, and Madelung deformity of the wrists).

  • In other patients, POI/POF is a part of familial syndromes and unusual clinical manifestations can be found, such as deafness in Perrault syndrome or blepharophimosis, eyelid dysplasia, and achondroplasia.

  • Pay attention to signs of thyroid disease, such as the presence of goiter, exophthalmos, bradycardia or tachycardia, and cold-and-dry or soft-and-warm skin.

  • Looking for clinical signs of adrenal insufficiency, such as orthostatic hypotension, hyperpigmentation, and decreased axillary and pubic hair, is important.

  • Other findings associated with the presence of autoimmune diseases may include vitiligo (often associated with thyroid and adrenal autoimmunity), premature graying of hair (in thyroid diseases), nail dystrophy and mucocutaneous candidiasis (in autoimmune polyglandular syndrome type 1), and alopecia areata and malar rash (in lupus).

  • Pelvic examination usually reveals atrophic vaginitis. However, some women have intermittent follicular function and produce enough estradiol to keep the vaginal mucosa well estrogenized. Usually, the ovaries are small and barely palpable. Enlarged ovaries could be found occasionally, as in some cases of immune oophoritis.

The diagnostic approach to patients with ovarian failure is as follows:

  • History

    • Last spontaneous menstrual cycle

    • Prior pelvic surgeries, irradiation, or chemotherapy

    • Symptoms of adrenal insufficiency, including the following:

      • Orthostatic hypotension

      • Skin hyperpigmentation

      • Unexplained weakness

      • Salt craving

      • Abdominal pain

      • Anorexia

    • Symptoms of hypothyroidism

    • Family history of POI/POF, male mental retardation (suggest Fragile X syndrome), autoimmune disorders

  • Physical examination

    • Signs of hypoestrogenism

    • Enlarged ovaries versus nonpalpable ovaries

    • Physical stigmata of Turner syndrome or other genetic syndromes, including the following: Short stature, webbed neck, low position of the ears, low posterior hairline, cubitus valgus, shield chest, short IV and V metacarpals

    • Signs of autoimmune diseases, Addison disease, and hypothyroidism

  • Tests

    • Pregnancy test

    • FSH, LH, estradiol

    • Standard blood chemistry - Fasting glucose, electrolytes, and creatinine

    • Karyotype

    • Test for fragile X chromosome (FMR1 premutation)

    • Thyroid-stimulating hormone (TSH)

    • Antithyroid peroxidase antibody

    • Serum adrenal antibodies

    • Bone density by dual-energy x-ray absorptiometry (DEXA) scan

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Physical

Patients with early-stage ovarian insufficiency alone have no physical findings. In overt POI and profound secondary ovarian insufficiency, physical examination may demonstrate atrophic vaginitis resulting from an estrogen deficiency. Ovarian insufficiency comprises a continuum along a decline in ovarian function. Patients with ovarian insufficiency frequently produce estrogen intermittently and may not demonstrate physical findings of estrogen deficiency. Thus, the finding of cervical mucus upon pelvic examination does not rule out a diagnosis of ovarian insufficiency.

  • Bimanual examination may reveal ovarian enlargement in patients who have lymphocytic oophoritis or steroidogenic enzyme defects.

  • Patients with Turner syndrome have characteristic physical stigmata, and a careful search for these should be conducted. However, patients with small interstitial deletions involving the X chromosome as a cause of ovarian insufficiency may not demonstrate these findings.

  • Autoimmune disorders known to be associated with POI have characteristic physical findings that should be elicited.

    • Changes in pigmentation, such as premature gray hair, may be associated with autoimmune hypothyroidism.

    • Vitiligo or increased pigmentation of the gums or the skin folds may herald Addison disease. Patients with Addison disease also may experience a loss of axillary and pubic hair because of reduced ovarian and adrenal androgen production.

    • Thyroid enlargement resulting from concomitant Hashimoto thyroiditis or Graves disease may be present.

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Causes

See Pathophysiology.

Ovarian insufficiency can develop as a result of an ovarian disorder. In this case, the clinical situation is termed primary ovarian insufficiency. Ovarian insufficiency also can develop due to inadequate ovarian stimulation coming from the hypothalamus and pituitary. In this case, the clinical situation is termed secondary ovarian insufficiency. Central ovarian insufficiency is a synonym for this condition (referring to the CNS origin of the disorder).

  • Causes of primary ovarian insufficiency include the following:

    • Iatrogenic

    • Abnormal karyotype

    • Isolated autoimmune ovarian failure

    • Premutation in the FMR1 gene

    • Autoimmune ovarian failure in association with other syndromes, such as autoimmune polyglandular failure, organ-specific autoimmunity, or immunoglobulin A deficiency

    • Rare genetic causes, such as enzyme deficiencies (galactosemia, 17-alpha hydroxylase, 17-20 desmolase, cholesterol desmolase), Perrault syndrome, and FSH receptor defect

    • Rare thymic disorders, such as DiGeorge syndrome, ataxia telangiectasia, or tumor

    • Pure gonadal dysgenesis

    • Idiopathic

    • Pseudo POI may be observed in patients with hypothyroidism, antibodies to gonadotropins, isolated gonadotropin deficiency, and gonadotropin-producing pituitary adenoma

  • Causes of secondary ovarian insufficiency include the following:

    • Eating disorders, exercise, psychiatric disorders, chronic debilitating disease

    • Drugs

    • Pituitary tumors, such as prolactinomas, or other tumors that secrete pituitary hormone, such as with Cushing syndrome or acromegaly

    • Pituitary necrosis (Sheehan syndrome)

    • Hypothalamic tumor

    • Craniopharyngioma

    • Kallmann syndrome

    • Infiltrative hypothalamic process, such as sarcoidosis

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