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Cited by 221Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsGenetic and Kidney Cyst Diseases

Treatment with Flutamide, Metformin, and Their Combination Added to a Hypocaloric Diet in Overweight-Obese Women with Polycystic Ovary Syndrome: A Randomized, 12-Month, Placebo-Controlled Study

Gambineri, Alessandra, Patton, Laura, Vaccina, Antonella, Cacciari, Mauro, Morselli-Labate, Antonio Maria, Cavazza, Carla, Pagotto, Uberto, Pasquali, Renato·2006·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2005-2250
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Abstract

CONTEXT: The few controlled trials performed so far indicate that the addition of metformin and/or flutamide to a hypocaloric diet in obese women with polycystic ovary syndrome (PCOS) effectively influences different phenotypic aspects of the syndrome. All these studies are, however, characterized by a short to medium period of treatment. OBJECTIVE: Our objective was to investigate the long-term effects of these therapies. DESIGN AND SETTING: We conducted a prospective, randomized, placebo-controlled trial at a medical center. PATIENTS: Of 80 overweight-obese women with PCOS, 76 completed the study. INTERVENTIONS: Patients were placed on a hypocaloric diet for the first month and then on a hypocaloric diet plus placebo, metformin (850 mg, orally, twice a day), flutamide (250 mg, orally, twice a day), or metformin plus flutamide for the subsequent 12 months (20 subjects in each group). MAIN OUTCOME MEASURES: We assessed clinical features, computerized tomography measurement of fat distribution, androgens, lipids, and fasting and glucose-stimulated glucose and insulin levels at baseline and after 6 and 12 months of treatment. RESULTS: After 6 months, compared with placebo, flutamide further decreased visceral/sc fat mass (P = 0.044), androstenedione (P < 0.001), dehydroepiandrosterone sulfate (P < 0.001), and hirsutism score (P < 0.001), whereas metformin further increased frequency of menstruation (P = 0.039). After 12 months, flutamide maintained the effects observed after 6 months on visceral/sc fat mass (P = 0.033) and androstenedione (P < 0.001), whereas it produced an additional decrease in dehydroepiandrosterone sulfate (P = 0.020) and hirsutism score (P = 0.019); metformin further improved the menstrual pattern (P = 0.013). Moreover, after 12 months, flutamide improved more than placebo the menstrual pattern (P = 0.008), glucose-stimulated glucose levels (P = 0.041), insulin sensitivity (P < 0.001), and low-density lipoprotein cholesterol levels (P = 0.003), whereas metformin decreased glucose-stimulated insulin levels (P = 0.014). The combination of the two drugs maintained the specific effect of each of the compounds, without any additive or synergistic effect. CONCLUSIONS: These findings add relevance to the usefulness of metformin and flutamide in the treatment of dieting overweight-obese PCOS women and provide a rationale for targeting different therapeutic options according to the required outcomes in the long term.

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  • Except for two studies (Hoeger et al., 2004; Gambineri et al., 2006), follow-up duration was 6 months or shorter.

    “Duration of follow-up, except for two studies (Hoeger et al. , 2004; Gambineri et al. , 2006), was 6 months or shorter.”

    From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Gambineri et al. , 2006

  • In Gambineri et al. (2006), IGT was seen in three (15%) subjects on lifestyle plus metformin and two (11%) on lifestyle plus placebo at baseline, decreasing to two (10%) and 0 respectively at 12 months.

    “In addition, IGT was seen in three (15%) subjects on lifestyle + metformin and two (11%) on lifestyle + placebo at baseline which decreased to two (10%) and 0 respectively at 12 months.”

    From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Gambineri et al. , 2006

  • In Gambineri et al. (2006), IFG was seen in three (15%) subjects on lifestyle plus metformin and two (11%) on lifestyle plus placebo, unchanged at study end (12 months).

    “In Gambineri et al. (2006), IFG was seen in three (15%) subjects on lifestyle + metformin and two (11%) on lifestyle + placebothat were unchanged at study end (12 months).”

    From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Gambineri et al. , 2006

  • Two studies lasting 12 months and 48 weeks provided data on BMI, testosterone, SHBG, FAI, menstruation, fasting glucose, glucose AUC, and insulin AUC.

    “Data on BMI, testosterone, SHBG, FAI, menstruation, fasting glucose, glucose AUC and insulin AUC were also available from two studies with durations of 12 months and 48 weeks (Hoeger et al. , 2004; Gambineri et al. , 2006).”

    From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Gambineri et al., 2006

  • Insulin resistance was assessed in five of nine studies comparing lifestyle plus metformin with lifestyle plus placebo.

    “Insulin resistance was assessed in five of nine studies comparing lifestyle + metformin with lifestyle + placebo (Pasquali et al. , 2000; Hoeger et al. , 2004; Gambineri et al. , 2006; Ladson et al. , 2011a, b).”

    From Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis (2015) · cites this paper as Gambineri et al. , 2006

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Authors
Gambineri, A., Patton, L., Vaccina, A., Cacciari, M., Morselli-Labate, A. M., Cavazza, C., Pagotto, U., & Pasquali, R.
Affiliations
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
  • Division of Endocrinology, Department of Internal Medicine, and Center for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Corresponding author
Pasquali, Renato
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2006-10-01
Volume
91
Issue
10
Pages
3970-3980
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2005-2250
OpenAlex
W2014108789
Cited by
221
References
48
Citations by year
2026: 4 · 2025: 14 · 2024: 3 · 2023: 8 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 7 · 2018: 14 · 2017: 10 · 2016: 7 · 2015: 20 · 2014: 12 · 2013: 10 · 2012: 9
FWCI
17.46
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
polycystic ovary syndrome, flutamide, metformin, hypocaloric diet, obesity, overweight women, long-term treatment outcomes, visceral fat, androgen levels, hirsutism, menstrual pattern, insulin sensitivity, glucose-stimulated insulin secretion, lipid profile, body fat distribution, combination therapy, weight loss, insulin resistance, androgen receptor antagonists
MeSH terms
Adipose Tissue, Adult, Energy Intake, Diet, Reducing, Drug Therapy, Combination, Female, Flutamide, Humans, Insulin Resistance, Metformin, Obesity, Polycystic Ovary Syndrome, Prospective Studies, Sex Hormone-Binding Globulin, Gonadal Steroid Hormones

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