1. No category

Managing PCOS, acne and
hirsutism in general practice
Johnny Loughnane
PCOS is a multi-system disease affecting one in 10 women. It requires
careful management and a holistic approach
POLYCYSTIC OVARY syndrome (PCOS) is the most common endocrine disorder of women, affecting 10% of women
of reproductive age. It affects the following:
UÊ-Žˆ˜ÊqÊ>V˜i]ʅˆÀÃṎÓ]ʓ>iÊ«>ÌÌiÀ˜Ê>œ«iVˆ>
UÊÊiÀ̈ˆÌÞÊqʈÌʈÃÊ̅iʓœÃÌÊVœ““œ˜ÊV>ÕÃiʜvÊ>˜œÛՏ>̜ÀÞʈ˜fertility
UÊÊiÌ>LœˆVÊqÊ*
"-ʈÃÊ>ʓ>œÀÊÀˆÃŽÊv>V̜ÀÊvœÀÊ`iÛiœ«“i˜ÌÊ
œvÊÌÞ«iÊÓÊ`ˆ>LiÌið
PCOS is therefore a multi-system disease and all aspects
˜ii`Ê̜ÊLiÊLœÀ˜iʈ˜Ê“ˆ˜`Ê܅i˜Ê“>˜>}ˆ˜}Ê«>̈i˜Ìð
Diagnosis
ˆ>}˜œÃˆÃʈÃÊL>Ãi`ʜ˜Ê̅iÊ«ÀiÃi˜ViʜvÊ>˜ÞÊÌܜʜvÊ̅iÊvœlowing:
UÊ*œÞVÞÃ̈VʜÛ>ÀˆiÃ
UÊ"ˆ}œ‡œÛՏ>̈œ˜ÊœÀÊ>˜œÛՏ>̈œ˜
UÊ
ˆ˜ˆV>Ê>˜`ɜÀÊLˆœV…i“ˆV>Ê>˜`Àœ}i˜ÊiÝViÃðÊ
>ÀÞÊ`iÃVÀˆ«Ìˆœ˜ÃʜvÊ*
"-ÊÜiÀiÊL>Ãi`ʜ˜ÊœÛ>Àˆ>˜Ê“œÀ«…œœ}ÞÊ­VÞÃÌÃÊۈÈLiʜ˜ÊՏÌÀ>Ü՘`ÊÃV>˜®°Ê/…ˆÃʈÃʘœÌʘœÜÊ
essential for diagnosis. Neither is a hormone profile essential for diagnosis. A woman with acne or hirsutism (clinical
>˜`Àœ}i˜Ê iÝViÃÃ®Ê >˜`Ê œˆ}œ“i˜œÀÀ…œi>Ê ­œˆ}œ‡œÛՏ>̈œ˜®Ê
…>ÃÊLÞÊ`ivˆ˜ˆÌˆœ˜Ê*
"-Ê>˜`ʘii`ÃʘiˆÌ…iÀÊՏÌÀ>Ü՘`ÊÃV>˜Ê
nor hormone analysis to confirm the diagnosis.
Hormonal analysis
/…iÊ “>ˆ˜Ê «ÕÀ«œÃiÊ œvÊ >˜ÞÊ ˆ˜ÛiÃ̈}>̈œ˜ÃÊ ˆÃÊ ÌœÊ iÝVÕ`iÊ
other causes of hyperandrogenism and oligo-ovulation. A
hormone profile (follicle stimulating hormone, luteinizing
…œÀ“œ˜iÊ >˜`Ê œiÃÌÀ>`ˆœ®Ê ÌœÊ iÝVÕ`iÊ …Þ«œ}œ˜>`ˆÃ“Ê œÀÊ Àiduced ovarian reserve (premature ovarian failure) is rarely
ˆ˜`ˆV>Ìi`°Ê /…iÞÊ >ÀiÊ ˜œÌÊ ˜ii`i`Ê vœÀÊ ÀœṎ˜iÊ V>ÀiÊ œvÊ *
"-Ê
patients.
vÊޜÕÊ>ÀiÊVœ˜ViÀ˜i`Ê̅>ÌÊ̅iÀiʓ>ÞÊLiÊ>˜Ê>ÌiÀ˜>̈ÛiÊÀi>ܘÊvœÀÊ̅iÊ«>̈i˜Ì½ÃʅޫiÀ>˜`Àœ}i˜ˆÃ“Ê̅iÊLiÃÌÊÌiÃÌÊ̜Ê`œÊˆÃÊ
>ÊvÀiiÊÌiÃ̜ÃÌiÀœ˜iʏiÛi°ÊvÊ̅iʏiÛiÊˆÃÊ}Ài>ÌiÀÊ̅>˜Ê`œÕLiÊ
the upper limit of the normal range, further investigation is
indicated to outrule more sinister causes of hyperandro}i˜ˆÃ“°Ê/…iʜÀ>ÊVœ˜ÌÀ>Vi«ÌˆÛiÊ«ˆÊ˜ii`ÃÊ̜ÊLiÊ`ˆÃVœ˜Ìˆ˜Õi`ÊvœÀÊvœÕÀÊ̜ÊÈÝÊÜiiŽÃÊLivœÀi…>˜`]Ê>ÃʈÌʏœÜiÀÃÊ̅iʏiÛiÊ
of free testosterone.
Consider testing for more serious pathology, including
androgen secreting tumours, when:
UÊ/…iÀiʈÃÊ>ÊÀ>«ˆ`ʜ˜ÃiÌʜvÊÃiÛiÀiÊ>V˜iɅˆÀÃṎÓ
UÊ/…iÊ«>̈i˜ÌʈÃʜ`iÀ
UÊ/…iÊ«>̈i˜Ì½ÃÊۜˆViʅ>ÃÊ`ii«i˜i`
UÊ
ˆÌiÀœ“i}>ÞʈÃÊiۈ`i˜Ì°ÊÊ
PCOS patients have high rates of hyperinsulinaemia and
dyslipidaemia. If PCOS is diagnosed, an oral glucose toler>˜ViÊ ÌiÃÌÊ >˜`Ê v>Ã̈˜}Ê ˆ«ˆ`ÃÊ Ã…œÕ`Ê LiÊ V…iVŽi`Ê ˆvÊ Ê ˆÃÊ
}Ài>ÌiÀÊ̅>˜ÊÓxʜÀÊ>ÊvˆÀÃ̇`i}ÀiiÊÀi>̈Ûiʅ>ÃÊÌÞ«iÊÓÊ`ˆ>LiÌiðÊ
Some 30% to 40% will have impaired glucose tolerance and
Óx¯Ê̜Êxä¯Ê…>ÛiÊ̅iʓiÌ>LœˆVÊÃޘ`Àœ“i°Ê/i˜Ê«iÀÊVi˜ÌÊ܈Ê
iÛi˜ÌÕ>ÞÊ`iÛiœ«Ê`ˆ>LiÌiðÊ/…iÃiÊÀˆÃŽÃÊiëiVˆ>Þʅœ`ÊvœÀÊ
women who are overweight.
Management
"LiÈÌÞÊ ˆÃÊ ÛiÀÞÊ Vœ““œ˜Ê >˜`Ê >Ê ivvœÀÌÃÊ Ã…œÕ`Ê LiÊ i“ployed to reduce weight in those who are overweight.
Hyperinsulinism and insulin resistance are root causes
œvÊ “œÃÌÊ «ÀœLi“ÃÊ ˆ˜Ê *
"-°Ê iÌvœÀ“ˆ˜Ê ˆ˜VÀi>ÃiÃÊ ˆ˜ÃՏˆ˜Ê
sensitivity and has promised much in managing PCOS. It
…>ÃÊ ÌœÊ LiÊ Ã>ˆ`Ê Ì…>ÌÊ ˆÌÊ …>ÃÊ Lii˜Ê `ˆÃ>««œˆ˜Ìˆ˜}Ê ˆ˜Ê Vˆ˜ˆV>Ê
practice. Consider metformin if PCOS is associated with
impaired glucose tolerance, especially if the patient has
Lii˜Ê՘>LiÊ̜ÊÀi`ÕViÊÜiˆ}…̰ʘÊÌiÀ“ÃʜvÊ«Àœ“œÌˆ˜}ʜÛÕlation it is inefficient when compared to clomiphene. Use in
>V˜iÊ>˜`ʅˆÀÃṎÓʅ>ÃÊŜܘÊÛ>Àˆ>LiÊ>˜`Ê`ˆÃ>««œˆ˜Ìˆ˜}Ê
results.
/…iÊi˜`œ“iÌÀˆÕ“ʈ˜Ê*
"-Ê«>̈i˜ÌÃÊ܈̅ʜˆ}œ“i˜œÀÀ…œi>Ê
ˆÃÊiÝ«œÃi`Ê̜Ê՘œ««œÃi`ʜiÃÌÀœ}i˜°Ê/…ˆÃʏi>ÛiÃÊ«>̈i˜ÌÃÊ>ÌÊ
ˆ˜VÀi>Ãi`Ê ÀˆÃŽÊ œvÊ i˜`œ“iÌÀˆ>Ê …Þ«iÀ«>È>Ê >˜`Ê V>ÀVˆ˜œ“>°Ê
7œ“i˜Ê܅œÊLii`ʏiÃÃÊ̅>˜ÊvœÕÀÊ̈“iÃÊ>ÊÞi>ÀÊŜՏ`ʅ>ÛiÊ
one of:
UʜÜÊ`œÃiÊVœ“Lˆ˜i`Ê"
*]Êi}°Ê9>ӈ˜
UÊÊ
ÞVˆV>Ê«Àœ}iÃÌiÀœ˜iÊqʓi`ÀœÝÞ«Àœ}iÃÌiÀœ˜iÊ>ViÌ>ÌiÊvœÀÊ
£äÊ`>ÞðÊ7ˆÌ…`À>Ü>Ê܈ÊLiÊvœœÜi`ÊLÞÊ>Ê«ÀœÌiV̈ÛiÊ܈̅`À>Ü>ÊLii`°Ê/…ˆÃʈÃÊÀi«i>Ìi`ÊiÛiÀÞÊ̅Àiiʓœ˜Ì…Ã
UʈÀi˜>Ê1
°Ê
Treatment of infertility
*>̈i˜ÌÃÊ Ã…œÕ`Ê LiÊ ÀiviÀÀi`Ê ÌœÊ >Ê }ޘ>iVœœ}ˆÃÌ°Ê œ“ˆ«…i˜iʈ˜`ÕViÃʜÛՏ>̈œ˜Êˆ˜ÊÇx¯Ê̜Ên䯰Ê/…iÀiʈÃÊ>ÊÈ}˜ˆvˆV>˜ÌÊ ÀˆÃŽÊ œvÊ “Տ̈«iÊ «Ài}˜>˜VÞÊ >˜`Ê V>ÀivÕÊ “œ˜ˆÌœÀˆ˜}Ê ˆÃÊ
indicated. Adding metformin to clomiphene does not seem
̜ÊLiʜvÊLi˜ivˆÌ°Ê
Hirsutism
Hirsutism is defined as the presence of terminal hair (long,
coarse, and pigmented) in women and girls, in a male an`Àœ}i˜Ê Ãi˜ÃˆÌˆÛiÊ «>ÌÌiÀ˜]Ê ˆi°Ê Li>À`Ê >Ài>]Ê œÜiÀÊ >L`œ“i˜Ê
HOT TOPICS 2010
9
HOT TOPICS
and chest. About 5%-15% of women of reproductive age
are affected. Management options are:
• Pills – low androgenicity, eg. Yasmin (ethinyl oestradiol 30
+ drospirenone) and Cilest (ethinyl oestradiol 35 + norgestimate 0.25mg). These arrest progression of hirsutism
but do not reverse it
• Dianette (cyproterone 2mg + ethinyl oestradiol 35), on
the other hand, gives substantial reduction of hirsutism. Because hormonal treatment reduces testosteronemediated hair growth, it is slow to work. Patients should
be warned of this
• Eflornithine 11.5% cream (Vaniqa). Retards hair growth
and can be used either alone or in combination with hormonal therapy. It is applied twice daily. Benefits are generally seen in two to three months. Discontinue if no benefit
seen at four months.
Acne
It is thought that the majority of women with severe acne
have PCOS, with reported rates as high as 83%. One-quarter of females over the age of 25 have some acne and 20%
of these need treatment. Acne in PCOS tends to persist for
very many years and has a high risk of recurrence after successful treatment. Therefore, whatever treatment works may
need to be continued for an extended period. Best results
are achieved with hormonal therapy, but be prepared for
high relapse rates on stopping therapy and for the possible
future need for extended hormonal use.
Suspect PCOS in acne patients with:
• Late onset acne
• Persistent acne
• Acne resistant to conventional therapies
• Concentration of lesions along the jaw line and chin
• Cyclic acne, with or without menstrual irregularities or hirsutism.
Thrombotic risk
For some time, controversy has surrounded the use of hormonal therapy in acne patients. Recent reports published in
the British Medical Journal produced more controversy, but
little, if any, light.
The argument centres on the thrombotic risk of differing
hormonal formulations. What we need for acne is a high
oestrogen content and a progestogen with low androgenic
potential. The higher the oestrogen level in a pill, the better
it is for acne.
Unfortunately, the higher the oestrogen level in a pill, the
higher the thrombotic risk. We just can’t get away from this
fact. So when deciding on hormonal therapy for acne, the
patient and their doctor make their choice after balancing
10
the benefits for acne against the possible slightly increased
risk of thrombosis.
What about the progestogen or anti-androgenic component of contraceptive pills? The picture, unfortunately, is
more confused. The studies are not conclusive but suggest
that drospirenone (Yasmin) and cyproterone acetate (Dianette) have similar thrombotic risk to desogestrel (Mercilon,
Marviol) and gestodene (Femodene) but a greater risk than
levonorgestrel (Ovranette). However, it has been argued
these observational studies are, in fact, unable to detect
if there are small differences in risk due to individual progesterones or antiandrogens. Increased thrombotic risk is a
class effect and is primarily dependent on oestrogen dose.
So why not use Ovranette? Although there is no evidence
from any well-conducted studies, many find levonorgestrel
can be androgenic for many women. It may precipitate or
aggravate acne, so for many it may not be the best option.
A good choice of hormonal therapy for a female patient should have a high oestrogen content and have antiandrogenic activity. Dianette (cyproterone 2mg + ethinyl
oestradiol 35) is our best fit for such requirements. Patients
should be made aware of the possible very small increased
thrombotic risk. Patients with an already increased risk of
thrombosis (obesity, metabolic syndrome, smoking) are
the patients we should worry about. These patients have
an increased background risk of thrombosis. They are at
increased thrombotic risk with all combined contraceptive pills. Advice on risk for this patient group should be
the same no matter what combined contraceptive they are
prescribed. Dianette may have a slightly higher risk (because of its high oestrogen dose). Dianette will, however,
give best results in treating the skin manifestations of hyperandrogenism, ie. acne and hirsutism.
Holistic approach
The strong message is that women with PCOS and who
are overweight should carefully assess their risk before
taking any form of combined contraception. Patients with
PCOS, but normal weight, are at much lower risk. All women with chronic acne and hirsutism need to understand the
level of risk of venous thromboembolism associated with
hormonal therapy.
In conclusion, PCOS should be considered a multisystem disease requiring a holistic approach to management. Those who are overweight have an increased risk of
thrombosis, which needs to be remembered if one is considering hormonal therapy. f
Johnny Loughnane is a GP in Co Limerick
HOT TOPICS 2010
Acne/Loughnane.-NH2 2
01/09/2010 16:44:39