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Cited by 118Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsAdrenal Hormones and Disorders

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome

Dahlgren, E., Landin, K., Krotkiewski, M., Holm, G., Janson, P.O.·1998·Human Reproduction
DOI 10.1093/humrep/13.10.2706
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Abstract

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

AI snapshot

Written from the paper’s full text.

TL;DR

In 28 women with PCOS who completed 6 months of treatment, ethinyloestradiol–cyproterone acetate (EO-CA) reduced hirsutism and serum androgens but decreased insulin sensitivity and increased triglycerides and Factor VII. Goserelin also reduced serum androgens and improved insulin sensitivity, but did not significantly reduce hirsutism; bone mineral density was unchanged in both groups.

Key findings

  • EO-CA (n=20): hirsutism score fell from 5.5 ± 1.4 to 3.4 ± 1.9 (P<0.05); total testosterone fell from 1.5 ± 0.8 to 0.9 ± 0.5 nmol/l and DHEAS from 5.3 ± 2.2 to 4.4 ± 2.2 mmol/l (both P<0.001). Insulin sensitivity decreased (glucose disposal per kg lean body mass, P<0.05; per kg bodyweight 8.74 ± 3.79 to 7.67 ± 3.85 mg/kg/min), serum insulin rose from 12.1 ± 7.9 to 15.5 ± 8.1 mU/l and C-peptide from 0.94 ± 0.40 to 1.11 ± 0.50 nmol/l (both P<0.01), triglycerides rose from 1.27 ± 0.64 to 1.88 ± 0.85 mmol/l (P<0.05), SHBG rose from 42.2 ± 35.5 to 167.8 ± 81.8 nmol/l (P<0.001), and Factor VII rose from 1.00 ± 0.24 to 1.12 ± 0.31 IU/ml (P<0.05).
  • Goserelin (n=8): hirsutism score was unchanged (4.6 ± 2.3 to 4.0 ± 2.4, NS); total testosterone fell from 2.9 ± 0.9 to 0.8 ± 0.6 nmol/l, androstenedione from 12.6 ± 3.4 to 6.2 ± 2.9 nmol/l (both P<0.001), and DHEAS from 4.18 ± 1.15 to 3.06 ± 0.98 mmol/l (P<0.01). Insulin sensitivity improved per kg lean body mass (P<0.05) but was unchanged per kg bodyweight (7.67 ± 4.36 to 8.31 ± 4.35 mg/kg/min), with unchanged BMI (30.9 ± 7.6 to 31.1 ± 7.4).
  • Bone mineral density was unaltered in both groups: EO-CA total body 1.22 ± 0.10 to 1.21 ± 0.10 g/cm²; goserelin 1.26 ± 0.06 to 1.24 ± 0.07 g/cm².
  • The authors conclude that EO-CA’s reduction in androgens was not paralleled by improved insulin sensitivity, probably due to ethinyloestradiol itself, whereas goserelin’s androgen reduction was accompanied by improved insulin sensitivity.

Methods

  • Nonrandomized 6-month intervention study: 32 women aged 19–38 with PCOS diagnosed by ovarian appearance on ultrasonography plus at least two of three clinical symptoms (oligomenorrhoea, obesity, hirsutism); 28 completed. Allocation depended on individual treatment need: women with predominantly hirsutism were offered EO-CA (n=20), and those with infertility were offered goserelin (n=8).
  • EO-CA was given cyclically (table footnote: ethinyloestradiol 50 µg for 21 days; cyproterone acetate 100 mg for 10 days, cycle days 1–10); goserelin 3.6 mg was implanted s.c. every 28th day. Women were their own controls, with clinical and laboratory investigations before and during the last 2 weeks of treatment.
  • Main measures included hirsutism score, insulin sensitivity by hyperinsulinaemic euglycaemic clamp, blood lipids, hormones, coagulation/fibrinolytic factors, blood pressure, body composition, and bone mineral density by dual energy X-ray absorptiometry. Non-parametric Mann–Whitney and Wilcoxon tests were used.

Limitations

  • Stated: the authors note the “small amount of material” and that further extended studies are needed to establish cause–effect relationships between hyperandrogenicity and insulin resistance. They also identify selection bias: treatment was not randomized, and the EO-CA group had a higher initial hirsutism score and longer duration of hirsutism.
  • Stated: one woman in the goserelin group had acanthosis nigricans and severe insulin resistance, raising the group’s mean insulin value; excluding her reduced mean insulin from 22.1 to 12.4 mU/l, with all other results unaffected.
  • Evident from the text: no placebo or untreated control group was used (women served as their own controls), group sizes were unequal (20 vs 8), all four dropouts occurred in the EO-CA group, and hirsutism was assessed by a subjective score.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/humrep/13.10.2706

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 13 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    EO-CA treatment increased serum insulin and C-peptide in women with PCOS (P < 0.01).

    “Serum insulin and C-peptide increased (P Ͻ0.01), but the C-peptide:insulin ratio was unchanged”
    Quote in the paperSubstantial claim
  • Findingown data

    Goserelin treatment did not change glucose disposal rate when calculated per kg bodyweight in women with PCOS.

    “but this parameter was unchanged when calculated in relation to bodyweight (7.67 Ϯ 4.36 versus 8.31 Ϯ 4.35 mg/kg bodyweight/min).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Goserelin treatment for 6 months decreased serum androgen concentrations, including total and free testosterone, DHEAS, and androstenedione, in women with PCOS.

    “In women treated with goserelin, serum androgen concentrations also decreased (P <0.001)”
    • Also stated in: § Effects of intervention with GnRH analogue (goserelin) · plain
      “Total and free testosterone concentrations decreased (Figure 2), as did serum concentrations of DHEA-S and androstenedione.”
    Quote in the paperSubstantial claim
  • Findingown data

    Goserelin treatment did not change SHBG in women with PCOS.

    “as was SHBG.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Goserelin treatment for 6 months did not significantly reduce hirsutism score in women with PCOS.

    “but there was no significant reduction of hirsutism.”
    • Also stated in: § Effects of intervention with GnRH analogue (goserelin) · plain
      “the hirsutism score was unchanged after treatment with goserelin for 6 months.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 4
  • May combine two claims. 12
  • Borderline: one of the tests for a substantial claim is unclear. 1
  • Classified as probably not a substantial claim. 8

  • The quote only partly states this claim.

    Findingown data

    EO-CA treatment for 6 months decreased serum androgen concentrations, including total and free testosterone and DHEAS, in women with PCOS (P < 0.001).

    “decreased serum androgen concentrations (P <0.001)”
    • Also stated in: § Effects of intervention with EO-CA · plain
      “Total and free testosterone (Figure 2) concentrations were reduced following treatment, as was the dihydroepiandrosterone (DHEAS) concentration, but androstenedione concentration was unchanged.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    EO-CA treatment for 6 months reduced hirsutism score in women with PCOS (P < 0.05).

    “Women treated with EO-CA showed a reduction in hirsutism (P <0.05)”
    • Also stated in: § Effects of intervention with EO-CA · plain
      “The hirsutism score was reduced after treatment with EO-CA for 6 months”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Goserelin treatment did not change free fatty acids or total cholesterol in women with PCOS.

    “Free fatty acids (0.77 Ϯ 0.22 versus 0.62 Ϯ 0.13 mmol/l) and total cholesterol (4.6 Ϯ 1.3 versus 5.0 Ϯ 0.9 mmol/l) were also both unchanged.”
    Quote in the paperNot a substantial claim

  • Borderline on S1 (asserted), S3 (load-bearing), S4 (based): unclear from the text. May combine two claims. The quote only partly states this claim.

    Findingown data

    EO-CA treatment did not affect blood pressure, bone mineral density, or anthropometric data in women with PCOS.

    “Bone mineral density in the total body remained unchanged (1.22 Ϯ 0.10 and 1.21 Ϯ 0.10 g/cm 2 at the beginning and end of treatment, respectively).”
    • Also stated in: § Effects of intervention with EO-CA · plain
      “no differences were seen in anthropometric data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Goserelin treatment did not change bone mineral density or anthropometric data in women with PCOS.

    “The bone mineral density was unaffected by goserelin (1.26 Ϯ 0.06 versus 1.24 Ϯ 0.07 g/cm 2 before and after treatment).”
    • Also stated in: § Effects of intervention with GnRH analogue (goserelin) · plain
      “There were no differences in anthropometric data after the treatment period”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    EO-CA treatment did not affect total cholesterol or free fatty acids in women with PCOS.

    “Free fatty acids were unchanged 2708 (0.67 Ϯ 0.26 versus 0.71 Ϯ 0.22 mmol/l), as was total cholesterol (5.00 Ϯ 0.99 versus 5.2 Ϯ 1.2 mmol/l).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Goserelin treatment for 6 months improved insulin sensitivity, measured as glucose disposal rate per kg lean body mass, despite unchanged body mass index, in women with PCOS (P < 0.05).

    “This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index.”
    • Also stated in: § Effects of intervention with GnRH analogue (goserelin) · plain
      “An improved glucose disposal rate (Figure 1) was noted when calculated in relation to lean body mass (P Ͻ0.05)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    EO-CA treatment did not affect PAI-1 activity or plasma fibrinogen in women with PCOS.

    “both PAI-1 activity (16.2 Ϯ 13.2 versus 11.8 Ϯ 16.5 U/ml) and plasma fibrinogen (3.17 Ϯ 0.73 versus 3.27 Ϯ 0.92 g/l) were unchanged.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Positive correlations exist between plasma insulin and serum testosterone in women with PCOS, indicating that hyperinsulinaemia contributes to the pathogenesis of the syndrome.

    “Positive correlations have been found between plasma insulin and serum testosterone in women with PCOS, indicating that hyperinsulinaemia contributes to the pathogenesis of the syndrome (Burghen et al., 1980;Shoupe and Lobo, 1984).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Burghen et al., 1980

      Not checked in the free run.

    • cites Shoupe and Lobo, 1984

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Factor VII is another risk factor for cardiovascular disease.

    “In addition, EO-CA increased Factor VII, which is another risk factor for cardiovascular disease (Meade et al., 1980)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Meade et al., 1980

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The improved insulin sensitivity with goserelin may be due to the reduction of serum androgens caused by goserelin.

    “The reason for an improved insulin sensitivity may be due to the reduction of serum androgens caused by goserelin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Treatment was not randomized; assignment depended on participants' individual need for medical treatment.

    “The treatment was not a randomized choice but rather was dependent on the participants' individual need for medical treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Objective and subjective measurements of hirsutism have been validated earlier.

    “Validating objective and subjective measurements of hirsutism have been made earlier (Azziz et al., 1995).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Azziz et al., 1995

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se.

    “The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The decrease of hirsutism score was only evident in the EO-CA group, which might be due to selection bias with women in the EO-CA group showing a higher initial score and a longer duration of hirsutism.

    “The decrease of hirsutism score was only evident in the EO-CA group, which might be due to a selection bias in this study population, with women in the EO-CA group showing a higher initial score and a longer duration of hirsutism.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The increase of T3 found in this study is due to increased thyroid-binding globulin induced by ethinyloestradiol.

    “The increase of T3 found in this study has been reported before in women on oral contraceptives and is 2710 due to increased thyroid-binding globulin induced by ethinyloestradiol.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Four women dropped out after beginning EO-CA treatment, and no data from the four nonattendants were included.

    “Four women began treatment with EO-CA but dropped out after between 1 and 5 months, two because of side effects (headache, heavy discharge), one because of surgery of a benign bone tumour, and one because of death in an accident.No data from the four nonattendants were included.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Insulin sensitivity was measured by a hyperinsulinaemic, euglycaemic clamp examination as previously described.

    “After an overnight fast, a hyperinsulinaemic, euglycaemic clamp examination was performed as previously described (De Fronzo et al., 1979).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites De Fronzo et al., 1979

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Bone mineral density measurements used a calibration phantom, with coefficients of variation of 0.4, 0.5 and 1.6% for total body BMD, lumbar spine L2-L4 and femoral neck, respectively.

    “During the entire study period, a calibration phantom (Comac-BME Quantitative Assessment of Osteoporosis Study Group) was used.The coefficients of variation (CV) between the measurements were 0.4, 0.5 and 1.6% for total body BMD, lumbar spine L2-L4 and femoral neck, respectively.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The women were their own controls.

    “The women were their own controls.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    EO-CA showed a negative impact on carbohydrate and lipid metabolism which was unrelated to its antiandrogenic action.

    “Thus, EO-CA in this study showed a negative impact on carbohydrate and lipid metabolism which was unrelated to its antiandrogenic action.”
    Quote in the paperSubstantial claim
21 of 21

  • The authors state this as an assumption.

    Therapeutic intervention affects the rate of growth and the quality of coarse hair rather than the extent of hirsutism.

    “It was assumed that therapeutic intervention had an impact on the rate of growth and the quality of coarse hair, rather than on the extent of hirsutism.”

  • The authors state this as an assumption.

    The glucose infusion rate during the clamp equals the tissue glucose disposal rate during the last 30 minutes when steady state is reached.

    “The glucose infusion rate during the clamp was assumed equal to the tissue glucose disposal rate during the last 30 min, when steady state was reached.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Ethinyloestradiol dose differs by a factor of 1,000

    Minor

    The study protocol states a dose of 50 mg, whereas the Table I footnote specifies 50 μg for the same EO-CA regimen.

1 of 1

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Related

Authors
Dahlgren, E., Landin, K., Krotkiewski, M., Holm, G., & Janson, P. O.
Affiliations
Sahlgrenska University Hospital (SE)
Venue
Human Reproduction
Publisher
Oxford University Press (OUP)
Published
1998-10-01
Volume
13
Issue
10
Pages
2706-2711
ISSN
  • 0268-1161 (ISSN-L)
  • 1460-2350
DOI
10.1093/humrep/13.10.2706
OpenAlex
W2119269482
Semantic Scholar
25b1d17622aa5a530f5fab9dbc8ac32499f82fd4
Cited by
118
References
33
Citations by year
2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 2
FWCI
4.70
Type
journal article
Language
en
Open access
closed
Locations
  • Human Reproduction (publishedVersion)
  • PubMed (publishedVersion)
Funders
Svenska Läkaresällskapet
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
polycystic ovary syndrome, antiandrogen therapy, hirsutism, insulin sensitivity, ethinyl estradiol, cyproterone acetate, goserelin, GnRH analogues, androgen reduction, serum lipids, bone mineral density, body mass index
MeSH terms
Adult, Androgen Antagonists, Androgens, Ethinyl Estradiol, Female, Hirsutism, Humans, Insulin Resistance, Lipids, Polycystic Ovary Syndrome, Goserelin, Cyproterone Acetate, Estradiol Congeners

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