Transcript Polycystic ovary syndrome Dr. Raghad Abdul-Halim Al-Issa

Polycystic ovary syndrome
Dr. Raghad Abdul-Halim AlIssa
The polycystic ovary syndrome
(PCOS) is a heterogeneous collection of
signs and symptoms that gathered
together form a spectrum of adisorder
with a mild presentation in some, while in
others a severe disturbance of
reproductive, endocrine and metabolic
function.
Definition of the PCOS
definition of the PCOS was agreed: namely the
presence of two out of the following three
criteria:
 Oligo- and/or anovulation;(oligomenorrhoea or
amenorrhoea)
 Hyperandrogenism (clinical and/or biochemical);
 Polycystic ovaries by ultrasound
Other aetiologies of hyperandrogenism and
menstrual cycle disturbance should be excluded by
appropriate investigations. The morphology of the
polycystic ovary, has been defined as an ovary with 12
or more follicles measuring 2–9 mm in diameter and
increased ovarian volume (>10 cm3)
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Genetics of PCOS:
Polycystic ovarian syndrome appears to
cluster in families, and it seems likely that
there is a gene or collection of genes that
are important in its development
The pathophysiology of PCOS
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Hypersecretion of androgens by the stromal theca cells of the
polycystic ovary leads not only to the cardinal clinical manifestation of the
syndrome, hyperandrogenism, but is also one of the mechanisms
whereby follicular growth is inhibited with the resultant excess of
immature follicles.
Hypersecretion of luteinizing hormone (LH) by the pituitary – a
result both of disordered ovarian-pituitary feedback and exaggerated
pulses of GnRH from the hypothalamus – stimulates testosterone
secretion by the ovary.
Furthermore, insulin is a potent stimulus for androgen secretion by
the ovary which, by way of a different receptor for insulin, does not exhibit
insulin resistance.
Insulin therefore amplifies the effect of LH, and additionally
magnifies the degree of hyperandrogenism by suppressing liver
production of the main carrier protein sex hormone binding
globulin (SHBG), thus elevating the ‘free androgen index’. It is a
combination of genetic abnormalities.
combined with environmental factors, such as nutrition and body
weight, which then affect expression of the syndrome.
Clinical features:
• Oligomenorrhoea/amenorrhoea: this occurs in up to 65-75
per cent of patients with PCOS and is predominantly related
to chronic anovulation.
• Hirsutism: this occurs in 30-70 per cent of women.
• Subfertility: up to 75 per cent of women with PCOS who try
to conceive have difficulty doing so.
• Obesity: at least 40 per cent of patients with PCOS are
clinically obese.
• Recurrent miscarriage: PCOS is seen in around 50-60 per
cent of women with more than three early pregnancy losses.
• Acanthosis nigricans: areas of increased skin pigmentation that
are velvety in texture and occur in the axillae and other
flexures occur in around 2 per cent of women with PCOS.
Laboratory tests:
• Elevated testosterone levels.
• Decreased sex hormone binding globulin (SHBG)
levels.
• Elevated LH levels.
• Elevated LH:FSH ratio.
• Increased fasting insulin levels.
It is important to note that total testosterone levels
may be only marginally elevated (or even normal)
in women with PCOS. Free testosterone is higher
than normal, since SHBG levels are low.
Testosterone levels of > 5 nmol/L should prompt a
search for an androgensecreting tumour.
Management of the polycystic
ovary syndrome:
Treatment
There is no treatment for PCOS as such.
Treatment should be directed at the
symptoms that the patient complains of:
OBESITY
The clinical management of a woman with PCOS should be
focused on her individual problems. Obesity worsens both
symptomatology and the endocrine profile and so obese
women (BMI >30 kg/m2) should therefore be encouraged to
lose weight. Weight loss improves the endocrine profile, the
likelihood of ovulation and a healthy pregnancy. Much has
been written about diet and PCOS.
 The right diet for an individual is one that is practical,
sustainable and compatible with her lifestyle. It is sensible to
keep carbohydrate content down and to avoid fatty foods. It
is often helpful to refer to a dietician.
 Metformin has not been shown to be valuable to aiding
weight reduction.
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Oligomenorrhoea/amenorrhoea
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Women with PCOS tend to be anovulatory, but to have normal or
high oestrogen levels.Without treatment, there is a theoretical risk
that unopposed oestrogenic stimulation of the endometrium may
increase the risk of endometrial cancer.
Additionally, oligomenorrhoeic women with PCOS tend to have
infrequent but heavy bleeds, as the endometrium that develops
under the influence of oestrogen eventually becomes unsustainable
and sheds. For these reasons, cyclical progesterone is often useful
in the treatment of women with PCOS, in order to induce regular
menstruation and to protect the endometrium. Oral progesterone
should be given for at least 10 days in each month (e.g.
medroxyprogesterone acetate 10 mg daily for 10 days).
An alternative treatment for women who do not wish to conceive
is the oral contraceptive pill. Since PCOS is driven in part by insulin
resistance, it
is not surprising that metformin, a drug that increases insulin
sensitivity, is partially effective in its treatment.
Hirsutism
Hirsutism arises from the growth-promoting
effects of androgen at the hair follicle.
Some of these growth-promoting effects are
irreversible, even when androgen levels fall.
Thus treatments aimed at reducing
testosterone levels will not restore the hair
to its pre-PCOS pattern. However, lowering
free androgen levels will slow the rate of
hair growth, which most patients see as a
benefit.
The possible treatment options
include the following.
• Cyproterone acetate: an anti-androgen that competitively inhibits the androgen
receptor. It may be given either as a low dose (in the form of the contraceptive pill
Dianette, which consistsof cyproterone acetate 2 mg and 35 mcg of
ethinylestradiol) , or at a higher dose of 50-100 mg daily. If the higher dose is
chosen, it is usual to give it for the first 10 days of each month, initially in
combination with oestrogen, and then followed by oestrogen alone for a further 11
days - the 'reverse sequential regimen'. A low-dose oral contraceptive may be given
as an alternative to oestrogen in this regimen.
• Metformin: a recent study showed metformin and Dianette to have similar efficacies
on both subjective and objective measures of hirsutism in women with PCOS.
• GnRH analogues with low-dose HRT: this regime should be reserved for women
intolerant to other therapies, or for short-term treatment, since bone loss is an
inevitable side effect.
• Surgical treatments aimed at destroying the hair follicle, such as laser or electrolysis:
surgical treatments are effective permanent methods of
hair removal. Some, such as electrolysis, are Associated with side effects such as
scarring.
•AnewCOCP,(Yasmin (3 mg drospirenone and 30 mcg ethenylestradiol)may also
be of benefit
spironolactone, Flutamide and finasteride are not routinely prescribed because of
potential adverse effects.
INFERTILITY
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combination of exercise and diet to achieve weight
reduction is important to improve the prospects of both
spontaneous and drug induced ovulation. In addition,
overweight women with PCOS are at increased risk of
obstetrical complications including gestational diabetes
mellitus and pre-eclampsia.Ovulation can be induced
with the anti-oestrogen clomifene citrate (50–100
mg) taken from days 2–6 of a natural or artificially
induced bleed. Clomifene citrate should only be
prescribed in a setting where ultrasound monitoring is
available (and performed) to minimize the10% risk of
multiple pregnancy and to ensure that ovulation is taking
place
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The therapeutic options for patients with anovulatory infertility who are
resistant to anti-oestrogens are either parenteral gonadotropin therapy
or laparoscopic ovarian diathermy. Because the polycystic ovary is
very sensitive to stimulation by exogenous hormones, it is very important
to start with very low doses of gonadotropins and follicular development
must be carefully monitored by ultrasound scans. The advent of
transvaginal ultrasonography has enabled the multiple pregnancy rate to be
reduced to less than 5% because of its higher resolution and clearer view
of the developing follicles.
Close monitoring should enable treatment to be suspended if more than
two mature follicles develop, as the risk of multiple pregnancy increases.
Women with the polycystic ovary syndrome are also at increased risk of
developing the ovarian hyperstimulation syndrome (OHSS).
Ovarian diathermy is free of the risks of multiple pregnancy and ovarian
hyperstimulation and does not require intensive ultrasound monitoring .
Laparoscopic ovarian diathermy has taken the place of wedge
resection of the ovaries (which resulted in extensive peri-ovarian and
tubal adhesions), and carries a reduced risk of multiple pregnancy
compared with gonadotropin therapy in the treatment of clomiphineinsensitive PCOS.
In summary
• Management is symptom orientated.
• If obese, weight loss improves symptoms and endocrinology and should be
encouraged. A GTT should be performed if the BMI is >30 kg/m2. Dietary
advice and exercise are essential components of a weight-reducing
programme. Anti-obesity drugs or surgery may be indicated.
• Menstrual cycle control may be achieved by cyclical oral contraceptives or
progestogens.
• Ovulation induction may be difficult and require progression through various
treatments which should be monitored carefully to prevent multiple
pregnancy.
• Hyperandrogenism is usually managed with Dianette, containing
ethinyloestradiol in combination with cyproterone acetate.
AnewCOCP,(Yasmin) may also be of benefit.
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Alternatives include spironolactone. Flutamide and finasteride are not
routinely prescribed because of potential adverse effects. Reliable
contraception is required.
• Insulin-sensitizing agents (e.g. metformin) are showing promise for ovulation
induction but require further long-term evaluation and should only be
prescribed by endocrinologists/reproductive endocrinologists. Weight loss
is not guaranteed
Long-term sequleae
Emerging evidence suggests that women with
PCOS are at increased risk of developing diabetes
and cardiovascular disease ( e.g ischemic heart
diseases, dyslipidemia, hypertension) later in life.
 However, at present there is no evidence that
they would benefit from any pharmacological
intervention prior to the development of
established disease. Clearly, however, lifestyle
advice (such as dietary modification and
increasing exercise) is appropriate.
 PCOS is regareded as a risk for endometrial
hyperplasia and endometrial adenocarcinoma.
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GOOD LUCK