Weight Gain After Oophorectomy Among Women with a <i>BRCA1</i> or <i>BRCA2</i> Mutation

Kotsopoulos, Joanne; Lubiński, Jan; Neuhausen, Susan L.; Gronwald, Jacek; Lynch, Henry T.; Huzarski, Tomasz; Demsky, Rochelle; Foulkes, William D.; Senter, Leigha; Friedman, Susan J.; Ainsworth, Peter; Sun, Ping; Narod, Steven A.

doi:10.2217/whe.15.4

Cited by 2 publications

(3 citation statements)

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“…Our findings support those of the Framingham Heart Study which demonstrated that although postmenopausal women have increased weight and visceral adipose tissue than younger women, this association is predominately due to age rather than menopause ( 17 ). It also supports the findings of Kotsopoulos et al, who found that oophorectomy in women with BRCA 1 and BRCA 2 mutation was not associated with significant weight gain ( 7 ).…”

Section: Discussionsupporting

confidence: 90%

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WHAM—A Prospective Study of Weight and Body Composition After Risk-Reducing Bilateral Salpingo-oophorectomy

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Krejany

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Body weight and composition may change over the natural menopause transition. Whether surgical menopause has similar effects, and the impact of HRT, are unknown. Understanding the metabolic effects of surgical menopause will inform clinical care. Objective To prospectively measure weight and body composition over 24-months following surgical menopause compared to a similar comparison group who retained their ovaries. Methods Prospective observational study of weight change from baseline to 24-months in 95 premenopausal women at elevated risk of ovarian cancer planning risk-reducing oophorectomy (RRSO) and 99 comparators who retained their ovaries. Change in body composition from baseline to 24-months was also assessed by DXA in a subgroup of 54 women who underwent RRSO and 81 comparators who retained their ovaries. In the sub-group, weight, fat mass, lean mass, and abdominal fat measures were compared between groups. Results At 24-months both groups had gained weight (RRSO 2760 ± 4860 g vs Comparators 1620 ± 4540 g) with no difference between groups (mean difference 730 g; 95% CI 920 g, 2380 g; p = 0.383). In the body composition subgroup, there was no difference in weight between groups at 24-months (mean difference 944 g; 95%CI -1120 g, 2614 g; p = 0.431). RRSO women may have gained slightly more abdominal visceral adipose tissue (mean difference 99.0 g; 95% CI 8.8 g, 189.2 g, p = 0.032) but there were no other differences in body composition. There were also no differences in weight or body composition between HRT users and non-users at 24-months. Conclusion 24-months after RRSO, there was no difference in body weight compared with women who retained their ovaries. RRSO women gained more abdominal visceral adipose tissue than comparators, but there were no other differences in body composition. Use of HRT following RRSO had no effect on these outcomes.

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Section: Discussionsupporting

confidence: 90%

“…Women at elevated risk of ovarian cancer must balance the established risks of RRSO for cancer risk reduction with the potential adverse sequelae of surgical menopause ( 4-6 ). In clinical practice, concerns of women contemplating RRSO include weight gain and change in body composition postsurgery ( 7-10 ).…”

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confidence: 99%

WHAM—A Prospective Study of Weight and Body Composition After Risk-Reducing Bilateral Salpingo-oophorectomy

Price

Finch

Krejany

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Thus, the effect of gonadectomy is consistent with sex-neutral obesity development in Mito-Ob, as observed previously during their phenotypic characterization [ 14 ]. Wild-type mice started to gain weight after gonadectomy, supporting previous reports that indicated the absence of gonadal estrogens or androgens led to weight gain in rodents and humans with aging [ 29 – 31 ]. However, this change was not found to be associated with adipose tissue area.…”

Section: Discussionsupporting

confidence: 85%

Gonadectomy in Mito-Ob mice revealed a sex-dimorphic relationship between prohibitin and sex steroids in adipose tissue biology and glucose homeostasis

Ande

Mishra

2018

Biol Sex Differ

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BackgroundRecently, we have developed a novel transgenic mouse model by overexpressing prohibitin (PHB) in adipocytes, which developed obesity due to upregulation of mitochondrial biogenesis in adipocytes, hence named “Mito-Ob.” Interestingly, only male Mito-Ob mice developed obesity-related impaired glucose homeostasis and insulin sensitivity, whereas female Mito-Ob mice did not. The observed sex differences in metabolic dysregulation suggest a potential involvement of sex steroids. Thus, the main aim of this study is to investigate the role of sex steroids on the overall phenotype of Mito-Ob mice through gonadectomy, as well as direct effect of sex steroids on adipocytes from Mito-Ob mice in vitro.MethodsMito-Ob mice and wild-type CD-1 mice were gonadectomized at 12 weeks of age. Age- and sex-matched sham-operated mice were used as controls. Body weight, white adipose tissue, glucose tolerance, and insulin sensitivity were analyzed 3 months post-surgery. Differentiation of adipocytes isolated from female and male Mito-Ob mice were studied with and without sex steroids.ResultsGonadectomy significantly reduced body weight in Mito-Ob mice compared with sham-operated mice, whereas the opposite trend was observed in wild-type mice. These changes occurred independent of food intake. A corresponding decrease in adipose tissue weight was found in gonadectomized Mito-Ob mice, but depot-specific differences were observed in male and female. Gonadectomy improved glucose tolerance in male wild-type and Mito-Ob mice, but the effect was more pronounced in wild-type mice. Gonadectomy did not alter insulin sensitivity in male Mito-Ob mice, but it was improved in male wild-type mice. In primary cell cultures, testosterone inhibited adipocyte differentiation to a lesser extent in male Mito-Ob preadipocytes compared with the wild-type mice. On the other hand, preadipocytes from female wild-type mice showed better differentiation potential than those from female Mito-Ob mice in the presence of 17β-estradiol.ConclusionsPHB requires sex steroids for the development of obese phenotype in Mito-Ob mice, which differentially affect glucose homeostasis and insulin sensitivity in male and female. It appears that PHB plays sex- and adipose depot-specific roles and involves additional factors. In vitro studies suggested that PHB differently influenced adipocyte differentiation in the presence and absence of sex steroids. Overall, this study along with available information in the literature indicated that a multifaceted relationship exists between PHB and sex steroids, which may work in a cell/tissue type- and sex-specific manner.

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Weight Gain After Oophorectomy Among Women with a BRCA1 or BRCA2 Mutation

Cited by 2 publications

References 38 publications

WHAM—A Prospective Study of Weight and Body Composition After Risk-Reducing Bilateral Salpingo-oophorectomy

WHAM—A Prospective Study of Weight and Body Composition After Risk-Reducing Bilateral Salpingo-oophorectomy

Gonadectomy in Mito-Ob mice revealed a sex-dimorphic relationship between prohibitin and sex steroids in adipose tissue biology and glucose homeostasis

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