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International Journal of Gynecology and Obstetrics (2007) xx, xxx–xxx
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Insulin resistance causing severe postmenopausal hyperandrogenism Ebaa Al-Ozairi a,⁎, Enid Michael b , Richard Quinton a a b
Department of Endocrinology, Royal Victoria Infirmary and University of Newcastle-upon-Tyne, Newcastle, UK Department of Women's Health, Royal Victoria Infirmary and University of Newcastle-upon-Tyne, Newcastle, UK
Received 15 August 2007; received in revised form 28 August 2007; accepted 30 August 2007
KEYWORDS Insulin resistance; Hyperandrogenism; Postmenopause; Morbid obesity
A 56-year-old woman (gravida 6, para 2) complained of localized facial hirsutism. Menses had been regular. The patient's weight had progressively increased and a more rapid gain was experienced after menopause at 50 years of age. She had developed diabetes mellitus type 2, hypertension, and dyslipidemia by the age of 53. Examination revealed morbid central obesity (body mass index 46.2 kg/m2; waist circumference 120 cm), acanthosis nigricans and multiple skin tags indicative of insulin resistance, and a Ferriman–Gallwey score of 10 out of 36, but no virilization. Investigations confirmed marked biochemical hyperandrogenism with hyperinsulinemia (Table 1), and serum gonadotrophin levels appropriate for postmenopause. Serum cortisol levels were suppressed physiologically with dexamethasone suppression testing; however, the serum testosterone level failed to suppress. Ultrasound and com-
⁎ Corresponding author. Department of Diabetes and Metabolism, Floor 4 William Leech Building, Medical School, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, UK. Tel.: +44 7746723414; fax: +44 191 222 0723. E-mail address:
[email protected] (E. Al-Ozairi).
puted tomographic (CT) imaging showed normal ovaries and adrenals, with a thin endometrial stripe. Given the patient's obesity and comorbidities, we felt that the risks of a bilateral salpingo-oophrectomy outweighed any clinical benefits, unless there was a high pretest probability of ovarian neoplasia. Therefore, the patient underwent an 8-week period of intensive diet and lifestyle modification. This included simple resistance exercises at home, and prescription of orlistat 120 mg tablets taken 3 times a day with full dietetic support (600 kCal deficits). By the end of this period the patient had lost nearly 10% of her initial body weight and, 8 months later, had not regained any weight. Serum testosterone level was nearnormalized, with a proportional fall in fasting insulin level; repeat ultrasound showed a thin, linear endometrium. This case illustrates the centrality of hyperinsulinemia in postmenopausal as well as premenopausal hyperandrogenism. The patient exhibited metabolic syndrome with severe insulin resistance, clinically manifest as morbid obesity, diabetes, hypertension, lipid abnormalities, and acanthosis nigricans. The serum testosterone level was extremely high initially, raising the possibility of autonomous secretion by an ovarian neoplasm. However, loss of nearly 10% of the patient's initial body weight resulted in normalization of the serum testosterone level. The patient had already been on a full dose of metformin for diabetes treatment; however, with significant dietary modification, a modest home exercise program, and orlistat, major additional improvements in the patient's serum biochemistry were achieved. Postmenopausal women with severe insulin resistance syndromes may have serum testosterone levels of around
0020-7292/$ - see front matter © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2007.08.017 Please cite this article as: Al-Ozairi E, et al, Insulin resistance causing severe postmenopausal hyperandrogenism, Int J Gynecol Obstet (2007), doi:10.1016/j.ijgo.2007.08.017
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E. Al-Ozairi et al. Table 1
Fasting biochemical profile at baseline and after weight loss
Weight, kg Glucose (NR, 2.5–6.0 mmol/L) Insulin (NR, 1.6–10.9 mU/L) Testosterone (NR, 0–3.2 nmol/L) SHBG (NR, 17–114 nmol/L) Free testosterone a (NR, 0–25 pmol/L) Cortisol (NR: 190–650 nmol/L) 17-OHP (NR, 0–14 nmol/L
Baseline fasting
Post-DST
8 weeks
6 months
8 months
111 4.3 41.8 9.8 36 149 400 2.0
– – 8.6 – – b 50 –
95 4.0 12.9 3.3 48 48 – –
97 4.1 21.0 3.7 39 62 – –
95.5 4.0 14.8 3.4 46 51 – –
Abbreviations: NR, normal range; DST, dexamethasone suppression testing; SHBG, sex hormone binding globulin; 17-OHP, 17-hydroxyprogesterone. a Free testosterone estimated using a mass action formula incorporating testosterone and SHBG values [1].
10 nmol/L, and hyperandrogenism has been tentatively linked to metabolic syndrome [2,3]. However, this case shows the efficacy of weight loss and lifestyle modification in severe postmenopausal hyperandrogenism. A biochemical response to interventions aimed at reducing insulin resistance may indicate low probability of hyperandrogenism caused by neoplasm. Such cases are likely to become more common with the rapid increase in obesity rates.
[2] Barth JH, Jenkins M, Belchetz PE. Ovarian hyperthecosis, diabetes and hirsuties in post-menopausal women. Clin Endocrinol (Oxf) 1997;46:129–30. [3] Golden SH, Ding J, Szklo M, Schmidt MI, Duncan BB, Dobs A. Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: the atherosclerosis risk in communities study. Am J Epidemiol 2004;160:540–8.
References [1] Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–72.
Please cite this article as: Al-Ozairi E, et al, Insulin resistance causing severe postmenopausal hyperandrogenism, Int J Gynecol Obstet (2007), doi:10.1016/j.ijgo.2007.08.017
