Polycystic
Ovarian Syndrome Part 2
by Keith Mallinson
Blood samples
from women with PCOS show that gonadotrophin secretion is disordered
resulting in increased plasma LH relative to FSH levels. FSH peaks,
which characterise ovulatory cycles, are absent and therefore pro-ovulatory
follicular development ceases. Thus the granulosa cells do not acquire
a fully activated aromatase system and remain unresponsive to LH.
Because of this, healthy follicles in polycystic ovaries rarely
develop beyond 5mm. Oestrogens are normally converted from androgens
in the presence of aromatase which is decreased when high levels
of: H exists. In women with PCOS therefore, oestrogen synthesis
and production of oestradiol from granulosa cells is decreased and
atresia of the follicle occurs. This atresia causes a build up of
secondary interstitial tissue and ovarian stroma. This disorder
of gonadotrophin secretion causes anovulation.
Women with PCOS
have elevated plasma androgen levels i.e. raised serum concentration
of testosterone, and this may represent the most sensitive single
biochemical marker of PCOS. These increased androgens are secondary
to pulsatile release of LH by the pituitary and cause hirsutism
and can be associated with acne and oily skin.
Assessment of
serum levels of progesterone on day 21 of the menstrual cycle will
deternine whether ovulation has occurred by detecting high levels
of progesterone which is secreted by the corpus luteum. Other blood
tests may be performed to exclude other causes of hyperandrogenism,
such as Cushing's Disease, hyperprolactinaemia or thyroid dysfunction.
The third criteria
used to classify and diagnose PCOS are the characterisation of ovarian
abnormalities, with ultrasonography representing a recent and non-invasive
technique to identify any ovarian changes. Hughesdon (1982) describes
the polycystic ovary histologically as being typically increased
in size and although an average number of primordial follicles are
apparent, the number of ripening and atretic follicles present is
usually doubled. There is a tendency for the tunica to be increased
and it contains many collagen fibres. There is also an increase
in sub-cortical stroma and this is derived primarily from the atretic
follicles.
During atresia
there is a striking hypertrophy of the theca cells which then disperse
into the interstitial tissue. The increased number of follicles
measuring 2-10mm in diameter can be easily visualised with ultrasound.
These follicles are usually seen around the edge of the ovary and
give it a classical pearl-necklace appearance. Ultrasonography will
also demonstrate the increased stroma which typifies the polycystic
ovary. An excellent correlation has been shown between morphological
appearance, as observed on ultrasound, and that shown on histology
(Saxton et. al., 1990), thus ensuring ultrasound can be reliably
used for the diagnosis of PCOS.
As already noted
PCOS is a complicated and unpredictable disorder which generally
causes anovulation and therefore infertility. The treatment that
will be offered will be aimed at resolving this anovulation. One
of the earliest forms of treatment performed by Stein and Leventhal
(1935), known as ovarian wedge resection has now been largely abandoned
due to the need for laparotomy and the potential for development
of adhesions. This surgical procedure was found to achieve successful
ovulation in approximately 80% of women and ovarian diathermy has
been used recently as an effective alternative with similar results.
(Armar et. al., 1990).
The exact mechanism
by which either procedure induces ovulation is unclear. As H J van
Gelderp (1991) points out, most studies using these techniques have
demonstrated that serum androgens and oestrogen levels fall in the
post-operative period and this may eliminate the positive feedback
effect of these steroids on the pituitary. The LH levels will return
to normal and the normalisation of the FSH and LH ratio allows follicular
maturation to occur. This return to a normal ovulatory cycle is
thought to be only temporary but may enable women to achieve a pregnancy.
Anti-oestrogens
such as Clomiphene Citrate and Tamoxifen may be used to induce ovulation
in women with PCOS. They act by binding hypothalmic oestogen receptors
and therefore release the hypothalamus from the negative feedback
effects of endogenous oestrogens. This leads to an increase in FSH
and LH production, which then stimulates follicular growth. Ovulation
rates of 80% are usually achieved with clomiphene and the cumulative
pregnancy rate is 40-50% (Hammond et. al., 1983). This medication
should not be continued for more than six months as with prolonged
use the risk of developing invasive ovarian tumours is increased.
About the Author
Keith Mallinson
is CEO of http://www.medicalcontentsolutions.com
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