Is ovarian surgery effective for androgenic symptoms of polycystic ovarian syndrome?

REVIEW

Is ovarian surgery effective for androgenic symptomsof polycystic ovarian syndrome?

N. P. JOHNSON1 and KAYE WANG2

1University Division of Obstetrics and Gynaecology, National Women’s Hospital, Aucklandand 2Faculty of Medicine and Health Sciences, University of Auckland, New Zealand

Summary

The effectiveness of laparoscopic ovarian drilling for treatment of

anovulation in polycystic ovarian syndrome (PCOS) has been

proved. The role of ovarian surgery in the treatment of symptoms

related to hyperandrogenaemia, such as hirsutism and acne, has

been less clear. This review sought to evaluate the effectiveness of

ovarian surgery in the treatment of non-infertility symptoms related

to PCOS. A systematic literature review was undertaken, by

searching the Medline database for the years 1966 – 2002 inclusive.

The search yielded 19 studies recording the outcomes of hirsutism,

acne or androgen levels from surgical treatment for women with

PCOS: three assessed unilateral oophorectomy; two ovarian wedge

resection; and 14 ovarian drilling. There was no consensus of a clear

improvement in hirsutism or acne in women undergoing surgery.

There was a trend towards a decrease in serum androgen levels in

most studies. We conclude that, while there is evidence that ovarian

surgery may decrease androgen levels in some women with PCOS,

the evidence that this translates into a clear improvement in

hirsutism and acne is less clear. Further high quality clinical

research, including data from randomisation, would be required to

answer this question.

BackgroundPolycystic ovarian syndrome (PCOS) is a highly prevalentendocrinopathy, characterised by symptoms of hyperan-

drogenaemia and anovulatory infertility. The underlyingpathophysiology may be an increased insulin resistanceowing to a post-receptor defect in cellular response to

insulin. This has important implications for long-termhealth, including an increased risk of diabetes, hypertensionand dyslipidaemia, and poses increased cardiovasculardisease risk (Hopkinson et al., 1998). It became accepted

in Australasia to base the diagnosis of PCOS onultrasonographic confirmation of polycystic ovaries (PCO)in the context of typical symptoms (Jansen, 1994), but there

is increasing recognition that the biochemical and metabolicdisturbance characterise the condition more reliably thanovarian morphology (Nestler et al., 1998).

The short-term medical care of women with PCOS hasfocused on symptomatic control of hirsutism, acne andmenstrual dysfunction, or treatment of anovulatory inferti-

lity. Therapeutic strategies depend upon whether thewoman wishes to conceive—ovulation induction is acompletely separate approach to treatment of the othersymptoms of PCOS. Interventions for the management of

hirsutism related to PCOS include:

(a) weight loss;

(b) cosmetic measures for hair removal;(c) oral tablets containing cyproterone acetate 2 mg and

ethinylestradiol 35 mg;(d) anti-androgen medical treatment, usually taken in

conjunction with an oral contraceptive pill, whichcould include high-dose cyproterone acetate,spironolactone, flutamide or finasteride.

There is a proportion of women who do not have asatisfactory therapeutic response to the above conservative

and medical strategies for treatment. In addition, manywomen are not keen to take long-term medical treatmentwith the potential for side effects.

Given that excessive androgen production from theovarian stroma contributes to the syndrome, surgicalintervention has been raised as a possible long-termtreatment strategy for androgenic symptoms, such as

hirsutism or acne, in women with PCOS (Hamerlynck,1982). However, while surgery, in the form of ovariandrilling, is used as a treatment for infertility (Farquhar,

Vandekerckhove and Lilford, 2003), it has neither beenrecommended widely nor evaluated rigorously as atreatment for other symptoms. The potential surgical

treatments include ovarian drilling, ovarian wedge resec-tion, unilateral or bilateral oophorectomy or hysterectomywith bilateral salpingo-oophorectomy. There is no consen-

sus of opinion that women with hirsutism benefit from asurgical procedure to treat the syndrome although surgery,even bilateral ooporectomy, is occasionally requested bywomen, particularly those with symptoms resistant to

medical treatment.The aim of this review was to assess the success of

ovarian surgery performed for the primary indication of

treating symptoms of PCOS unrelated to infertility.

Search strategyThe search strategy for identification of relevant studies wasas follows.

(1) The Medline electronic database was searched usingOvid software (1966 – 2002 inclusive) using the

following keywords:

Correspondence to: Dr N. P. Johnson, Senior Lecturer and Consultant, University Department of Obstetrics and Gynaecology, National

Women’s Hospital, Auckland, New Zealand. Telephone: +64 9 6389919; Fax: +64 9 6309858; E-mail: [email protected]

Journal of Obstetrics and Gynaecology (November 2003) Vol. 23, No. 6, 599–606

ISSN 0144-3615 print/ISSN 1364-6893 online/03/060599-08 ª Taylor & Francis Limited, 2003

DOI: 10.1080/01443610310001604330

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Table I. Unilateral oophorectomy for symptoms of PCOS

Author/year Type of study Participants Intervention Outcomes Results

Hamerlynk, 1992 Observational study 10 women with PCOS Unilateral oophorectomy Serum testosterone,hairgrowth; meanfollow-up 30 months

Serum testosterone levels fellin all women, normalising ineight; then rose slightly in twoover 30 months’ follow-upLess frequent requirement forhair removal

Kaaijk et al., 1997 Case series Three women with clomipheneresistant PCOS-related infertilityand unilateral ovarian pathology

Unilateral oophorectomy Serum testosterone;follow-up 23 months

Testosterone levels decreasedin two women to upper limit ofnormal, unchanged in onewoman

Kaaijk et al., 1999 Observational study 14 women with PCOS andclomiphene-resistant anovulationor severe hirsutism

Unilateral oophorectomyby laparotomy

Hirsutism and serumtestosterone; follow-up 14 – 18 years

Subjective regression ofhirsutism in six of 11 women(complete resolution in one)and maintained during follow-upTestosterone levels normalisedin 10/13, decreased butremained elevated in 2/13,increased in 1/13

RCT= randomised controlled trial; DHEAS=dehydroepiandrosterone sulphate; LHRH= luteinising hormone releasing hormone.

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Table II. Ovarian wedge resection for symptoms of PCOS


Judd et al., 1976 Non-randomisedcontrolled study

Eight women withclomiphene-resistantPCOS vs. five womenundergoing hysterec-tomy for non-ovariandisease

Ovarian wedgeresection

Serum androgens;follow-up 35 days

Initial rise of androgens followed by afall in serum testosterone in womenundergoing wedge resection andthose undergoing hysterectomy

Vejlsted andAlbrechtsen, 1976

Observational study 12 women with PCOS Ovarian wedgeresection

Androgens, hirsutism;follow-up 6 – 18

No significant reduction in 17-ketosteroid excretion

months. Serum testosterone significantlyreducedNo regression of hirsutism in anycase, but frequency of hair removaldecreased


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Table III. Ovarian drilling for symptoms of PCOS


Aakvaag andGjoaness, 1985

Observational study 58 women with PCOS Laparoscopic ovarianelectrocautery

Serum androgens;follow-up 12months

Significant reduction of testosterone,androstenedione and DHEAS

Abdel Gadir et al.,1990

RCT 20 women with PCOS Laparoscopic ovarianelectrocautery(11 women) vs.intranasal LHRHspray

Serum testosterone Significant post-treatment reduction ofmean testosterone (similar to LHRH spraygroup)

Alborzi et al., 2001 Observational study 311 women withclomiphene-resistant PCOS

Laparoscopic ovariancauterisation

Serum androgenslevels; follow-up 10days

Significant reduction of testosterone andDHEAS levels; preoperative ovarian sizewas not a predictor of response

Amer et al., 2002 Observational study 116 anovulatorywomen with PCOS

Laparoscopic ovariandrilling

Hirsutism and acne Improvement in 10/43 women withhirsutism; 10/25 women with acne

Armar et al., 1990 Observational study 21 nulliparousoligomenorrhoeicwomen withclomiphene-resistant PCOS

Laparoscopic ovariandiathermy


Significant decrease in testosterone andandrostenedione, but no significant changein DHEAS

Balen and Jacobs,1994

RCT 10 women withclomiphene-resistant PCOS

Unilateral (fourwomen) vs. bilateral(six women) laparo-scopic ovariandiathermy

Serum testosterone No significant differences

Farhi et al., 1995 Observational study 22 women withclomiphene-resistant PCOS

Laparoscopic ovarianelectrocautery

Serum testosterone No significant decrease in serumtestosterone

Farquhar et al.,2002

RCT 50 women withclomiphene-resistant PCOS

Laparoscopic ovariandiathermy (29women) vs. gonado-trophin injections (21women)

Hirsutism, acne andserum testosterone

No significant changes in Ferriman Galweyscore, acne or serum testosterone inovarian diathermy group.

Gjoaness, 1984 Observational study 62 women with PCOS Laparoscopic ovarianelectrocautery

Hirsutism and acne 28 women with acne claimed animprovement; no results concerninghirsutism

(continued overleaf )

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Table III (continued )


Gjoaness, 1998 Observational study 165 infertile womenwith PCOS

Laparoscopic ovarianelectrocautery

Serum androgens;10 years (24 women),418 years (15women)

Significant decrease in serum testosterone2.76 to 1.25 nmol/l and androstenedione 8.1to 4.7 nmol/l, but DHEAS not significant until10-year follow-up

Greenblatt andCasper, 1987

Non-randomisedcontrolled study

Six women withclomiphene-resistantPCOS and six womenwith regular cyclesundergoinglaparoscopy forinfertility investigationor sterilisation

Laparoscopic ovarianelectrocautery vs.diagnostic laparo-scopy for infertilityinvestigation orsterilisation


Serum testosterone and androstenedionesignificantly decreased to nadir levels ondays 3 and 4 and did not occur in controls

Rossmanith et al.,1991

Observational study 11 women withclomiphene-resistantPCOS

Laparoscopic lasercoagulation of ovariansurfaces and cysts

Serum androgens;follow-up 6 – 8 weeks

Serum testosterone and androstenedionelevels significantly decreased; DHEAS levelsunchanged

Van der Weiden et al.,1989

Observational study 14 women withclomiphene-resistant PCOS

Laparoscopic ovariancautery

Serum androgens;follow-up 6 months

Testosterone and androstenedione levelsdecreased after surgery, but and rostene-dione levels tended to return to pre-treat-ment levels after 6 months

Zak and Pawelczyk,1998

Observational study 40 women withinfertility, anovulationand hyperandro-genaemi, 34 of whomhad oligo- oramenorrhoea

Laparoscopic ovariancauterisation

Serum testosterone Significant decrease in androgen level from0.94 to 0.7 ng/ml


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(a) *Polycystic ovaries/ or *Testosterone/ or *androgens/(b) limit (a) to humans

(c) Ovarian surgery/exp Laser Surgery/or exp Laparo-scopy/

(d) (b) and (c)

(e) Ovariectomy/ or oophorectomy.mp(f) (b) and (e)

The searches from points (d) and (f) above yielded

different studies.(2) The citation lists of relevant publications, review

articles and included studies were also searched.

All studies from the search strategy were scrutinisedand, if the study assessed an ovarian surgical interventionin women with PCOS where the outcomes hirsutism, acne

or serum androgen levels were assessed, the study wasincluded in the systematic review. The results of theseoutcomes, as far as could be ascertained from the

published material, are presented in Tables I – III.Although many of these studies were reporting ovulationor pregnancy as their primary outcomes, these outcomes

have not been considered as this was outside the scope ofthe review.

ResultsThe systematic literature search yielded 19 studiesreporting the outcomes for hirsutism, acne or serum

androgen levels following surgical treatment (unilateraloophorectomy, wedge resection, ovarian drilling) forwomen with PCOS as summarized in Tables I – III.

Hirsutism, acne and serum androgen levels were reportedcommonly as secondary outcome measures in trials wherefertility variables were the primary outcomes reported.Eighteen of the studies were published fully in peer-

reviewed journals and one was published in conferenceabstract form (Zak and Pawelczyk, 1998). There were eightpapers published in non-English language journals which

may have been of relevance; however, no translation hasbeen commissioned to date.

Of the 18 reports, three assessed the intervention

unilateral oophorectomy (Table I), two ovarian wedgeresection (Table II) and 13 laparoscopic ovarian drilling(Table III). No reports assessed bilateral oophorectomy,

whether or not associated with a hysterectomy. Of the 18studies, only five included a control group and only three ofthese five studies used a control group generated byrandomisation (Abdel-Gadir et al., 1990; Balen and Jacobs,

1994; Farquhar et al., 2002).Five studies addressed the outcome hirsutism (Vejlsted

and Albrechtsen, 1976; Hamerlynck, 1992; Kaaijk et al.,

1999; Amer et al., 2002; Farquhar et al., 2002), of whichonly Farquhar et al. (2002) used the objective measure ofthe Ferriman Galwey score. In this prospective randomised

trial, only two of the 15 patients with a Ferriman Galweyscore of greater than 8 showed objective improvementfollowing laparoscopic ovarian diathermy. In two further

studies, none of the cases observed a regression of hirsutismfollowing unilateral oophorectomy (Hamerlynck, 1992) andovarian wedge resection (Vejlsted and Albrechtsen, 1976),although less frequent necessity for hair removal techniques

suggests the rate of hair growth may have decreased post-surgery. Only one study reported regression and evencomplete disappearance of hirsutism in women undergoing

unilateral oophorectomy (Kaaijk et al., 1999).

The outcome for acne was mentioned in three of thestudies assessing laparoscopic ovarian drilling: two studies

reported an improvement in the acne problem in the studygroup (Gjoaness, 1984; Amer et al., 2002); the otherreported no change in acne for the majority of women

(Farquhar et al., 2002).Seventeen studies addressed serum androgen levels as an

outcome (Table II). Of these, 14 study authors claimed a

reduction in at least one of the serum androgen levels post-surgery, with no reduction concluded in three studiesassessing laparoscopic ovarian drilling (Balen and Jacobs,1994; Farhi et al., 1995; Farquhar et al., 2002). There was

less consensus over the duration of the decrease intestosterone level postoperatively. Van der Weiden et al.(1989) concluded that the decreased androgen levels tended

to return to pretreatment levels after 6 months, andspeculated that this might be due to renewed stromalproliferation; a long-term observational study concluded

that the early decrease in androgen after ovarian electro-cautery persisted for many years, with the mean testosteronevalue 18 years after ovarian electrocautery being only one-

half of the preoperative value (Gjoaness, 1998).Of the randomised trials, Abdel-Gadir et al. (1990) found

no evidence of a difference in post-treatment serumtestosterone between laparoscopic ovarian electrocautery

and intranasal luteinising hormone-releasing hormoneintranasal spray; Balen and Jacobs (1994) found nosignificant differences in serum testosterone between

unilateral and bilateral laparoscopic ovarian diathermy;Farquhar et al. (2002) found no significant differences inwomen’s Ferriman Galwey scores or whether acne was

present following laparoscopic ovarian diathermy comparedto gonadotrophin injection treatment; and did not find asignificant difference in serum testosterone levels before andafter laparoscopic ovarian diathermy, although pregnancy

outcomes were the primary outcomes assessed.

CommentLaparoscopic ovarian drilling has become an establishedfertility treatment option for women with clomiphene-

resistant anovulatory PCOS (Farquhar et al., 2003). Therole of surgery for non-fertility symptoms related to PCOS(such as hirsutism or acne) is less clear.

Women in the majority of the 19 reports in theliterature assessing unilateral oophorectomy, ovarianwedge resection and ovarian drilling experienced adecrease in serum androgen levels, although three studies

did not confirm a decrease in serum androgen levels(Balen and Jacobs, 1994; Farhi et al., 1995; Farquhar etal., 2002) and androgen levels were not assessed in one

study (Gjoaness, 1984). Ovarian surgery has not generallybeen demonstrated to have an effect on the severity ofhirsutism, but has been suggested to decrease hair growth

rate in some women (Vejlsted and Albrechtsen, 1976;Hamerlynck, 1982). There are insufficient and conflictingdata to assess acne as an outcome (Gjoaness, 1984; Amer

et al., 2002; Farquhar et al., 2002).The difficulty with drawing credible conclusions from

studies of ovarian surgery for women with PCOS is thatthey tend to focus on fertililty outcomes. More

importantly, for case series, observational studies andnon-randomised controlled studies, conclusions based onresults where there is no randomised control group are

prone to substantial bias. For example, while a decrease

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of androgens and even regression of hirsutism or acnemight be observed, if there is no appropriate control

group this effect cannot be distinguished from a possiblenatural evolution over time (which could conceivablyoccur in women with PCOS as they approach meno-

pause). The apparent decrease in androgen levelsfollowing ovarian surgery reported in some studiesprovides encouragement that ovarian surgery might be

effective in improving problems such as hirsutism or acne(symptoms typically related to hyperandrogenaemia).However, these symptoms reflect not only the serumandrogen levels, but also the end-organ response of skin

and hair follicles to androgens. There is a lack of data todetermine whether hirsutism and acne, the outcomes ofgreater importance to women than serum androgen levels,

are influenced by such surgery. Particularly lacking isevidence from randomised controlled trials (RCTs) thatovarian surgery is effective.

Theoretically, any effect of ovarian surgery might beexpected to be related to the effect of ovarian tissueablation, ranging from small effects from ovarian drilling,

through wedge resection, to unilateral oophorectomy. Theeffect of such surgery on ovulatory function may betemporary, albeit of variable time-frame (Farquhar et al.,2003), hence any effect on androgen levels might also be

temporary. On the other hand, any effect of bilateraloophorectomy on androgen levels and androgenicsymptoms is likely to be permanent. Our own limited

experience of four cases for whom laparoscopic bilateraloophorectomy for extreme hirsutism has been performedis of a uniform reduction of serum androgen levels in all

cases, but subjective improvement in hirsutism and acnein only two of four cases. There are no other reports ofbilateral oophorectomy for this indication in theliterature. Such surgery, even when performed laparosco-

pically, is not without potential complications. There isalso the implication of the issue of hormone replacementin young women undergoing bilateral oophorectomy, a

decision complicated further following publication of theWomen’s Health Initiative Study (2002). It is thereforeimportant to have clear evidence of a beneficial effect of

such surgery before this can be recommended in routineclinical practice. If a RCT was to be performed, in orderto have 80% power at the 95% confidence level to

demonstrate an improvement in 50% of women in thetreatment group vs. an improvement in, for instance, 25%of the women in the control group, 130 evaluatedrandomised participants would be required for randomi-

sation to laparoscopic ovarian surgery versus no surgery.The primary outcomes of subjective improvement inhairgrowth and acne would need to be supported by

secondary outcomes of objective measures of hirsutism(Ferriman Galwey Score) and acne, in addition toandrogen levels and any treatment (including surgical)

complications.

ConclusionWhile there is evidence that ovarian surgery may decreaseandrogen levels in some women with PCOS, the evidencethat this translates into a clear improvement in hirsutism

and acne (the outcomes important to women with PCOS) isless clear. Further high-quality clinical research, includingdata from randomisation, would be required to answer this

question.

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Is ovarian surgery effective for androgenic symptoms of polycystic ovarian syndrome?