Ovarian failure results when there are no eggs available for maturation.
With ovarian failure the fertility prognosis is poor unless donor
eggs are used. The FSH concentration (ideally with LH and estradiol
concentrations) can confirm ovarian failure. In one study, women
with gonadal (ovarian) failure and primary amenorrhea were consistently
found to have no follicular activity on pathology reports (of
the ovarian tissue) when the FSH concentration was greater than
40 IU/L. These data may not be entirely applicable to ovarian
failure with secondary amenorrhea, but consistently elevated FSH
concentrations (usually greater than 25 IU/L and certainly greater
than 40 IU/L) with a coincident low estradiol concentration (to
rule out a FSH producing pituitary tumor) and secondary amenorrhea
strongly suggests ovarian failure.
Menopause is the absence of menstruation due to the depletion
of eggs capable of maturation. The average age of menopause in
the USA is about 51-52 years old. Less than 1% of women have "menopause"
when younger than 40 years old, so that when this occurs it is
called "premature ovarian failure" or POF. There appear
to be two main causes of this accelerated loss of eggs such that
there is total depletion of maturation capable eggs at a very
young age (POF). First, there may be a chromosomal abnormality
in the X chromosome affecting the genes that regulate the rate
of egg loss. Second, autoimmune disease that produces antibodies
that can attack and destroy the ovaries is able to result in early
ovarian failure.
If POF occurs prior to 30 years of age, there is a chance that
the cause of ovarian failure is associated with an abnormal X
chromosome that actually contains Y chromosome (male) material.
It is very important to recognize when this is the case since
the ovaries containing Y chromosome material have a high chance
of malignant degeneration (about 25% develop highly malignant
cancers such as gonadoblastomas, dysgerminomas, or yolk sac tumors).
Therefore, any ovary with Y chromosome material should be removed
as early as possible (many of the cancers develop at less than
20 years age) to avoid this life threatening complication. Of
note is that many new Y chromosome probes are now available in
certain research centers and new Y specific probes are constantly
being developed. If available to the physician, special chromosomal
analysis including the use of these new Y chromosome probes should
be considered. It is not necessary to perform chromosomal analysis
if POF developed after the age of 30 since cancer formation after
this age is exceedingly rare.
It is expensive and not usually practical (at least in 1997) to
distinguish which of the types of causes has resulted in a particular
woman's POF (if occurring after the age of 30). Many deletions
or other genetic abnormalities in the X chromosome can result
in POF. These can occasionally be found with standard or site
directed chromosome analysis. The two clinical situations in which
this testing appears to be most reasonable (in addition to those
younger than 30) are when
* the woman with POF has a sister or daughter who might also
possess the X chromosome abnormality and has not yet undergone
POF.
In this situation, if an abnormality in the X chromosome is identified
in both the woman with POF and her sister (or daughter) then that
female relative could consider childbearing at an earlier age
since she may later develop POF.
* the woman with POF is short in stature, usually less than
5 foot 3 inches.
In a large series of patients with primary amenorrhea, it was
demonstrated that all women with a major X chromosome abnormality
were less than 63 inches tall (5 foot 3 inches) and up to one
third of these had other major organ system abnormalities (mostly
cardiovascular or renal). Therefore, if the woman with POF is
short a chromosome analysis looking for major X deletions or mosaic
cell lines should be considered. If identified, then autoimmune,
cardiovascular and renal (kidney) evaluations are in order.
Coincident autoimmune disease appears to occur in many women with
POF. More than 50% may have non-organspecific antibodies such
as ANA and Rheumatoid factor. Possibly 30% will have an associated
autoimmune disorder. Therefore, screening bloodwork for autoimmune
disease should be considered, including
- * a circulating TSH concentration and anti thyroid
antibodies levels,
- * an A.M. cortisol level, or the more demanding ACTH
stimulation test, to assess adrenal reserve since there is a relatively
high incidence of autoimmune adrenal insufficiency with autoimmune
POF
- * a complete blood count (CBC) and chemistry profile
to look for autoimmune parathyroid disease (calcium and phosphorus
concentrations) and hemolytic anemia (CBC).
In women with POF the likelihood of fertility is poor but not
impossible. Some women will have an occasional spontaneous ovulation
that might result in pregnancy. The incidence of this is not known
or predictable, but there seems to be a less than 5% chance of
spontaneous pregnancy. Pregnancy in women with POF has been associated
with the use of estrogen hormone replacement medication. The mechanism
underlying this association is not clear, with some postulating
(based on theory rather than data) that the estrogen administered
might enhance the number of FSH receptors on the follicles to
make them more responsive to the circulating FSH. The use of corticosteroids
to treat POF that has an autoimmune cause has not been uniformly
successful and is not generally advised. The use of fertility
medication has resulted in rare and unpredictable ovarian response
and is usually discouraged. If the FSH concentration is less than
the LH concentration and/or the estradiol concentration is greater
than 40 pg/ml (the amount required for a withdrawal flow) then
ovulation induction can be more reasonably considered. Hopefully,
the ongoing research in this area will provide clinicians with
more successful approaches to this difficult problem in the near
future.
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