Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model

doi:10.1016/j.genm.2009.04.004

Gender Medicine

Volume 6, Issue 1, April 2009, Pages 300-311

https://doi.org/10.1016/j.genm.2009.04.004 Get rights and content

Abstract

Background: With aging and menopause, which are associated with decreases in ovarian steroids such as 17β-estradiol (E₂), women might experience negative psychological symptoms, including anxiety and depression. Some women use E₂-based therapies to alleviate these symptoms, but E₂ has been associated with trophic effects that might increase vulnerability to some steroid-sensitive cancers, such as breast cancer, in both premenopausal and postmenopausal women.

Objective: This study investigated the relationships between the possible beneficial effects of E₂ on anxiety and depressive behaviors concurrent with trophic effects using an animal model of E₂ decline and replacement.

Methods: Dose-dependent effects of E₂ on affective, sexual, and motor behavior of young adult rats were studied. Ovariectomized (OVX) rats were administered the chemical carcinogen 7,12-dimethylbenz(a) anthracene (DMBA) 1.25 mg or inactive vehicle (vegetable oil; control) by gavage. E₂ (0.03 or 0.09 mg/kg) or vehicle was administered subcutaneously 44 to 48 hours before assessments of anxiety (light—dark transition), depression (forced swim test), sexual (lordosis), and motor (activity monitor) behaviors. Fourteen weeks after carcinogen exposure, E₂ concentrations in plasma and brain regions (cortex, hippocampus, and hypothalamus) were determined. Incidences and numbers of tumors and uterine weight were analyzed.

Results: Administration of E₂ (0.09 mg/kg) was associated with significant increases in antianxiety-like behavior in the light—dark transition task, antidepressant-like behavior in the forced swim test, and physiologic circulating and central E₂ concentrations compared with E₂ (0.03 mg/kg) and vehicle. Compared with vehicle, E₂ (0.9 > 0.3 mg/kg) was associated with significant increases in lordosis and uterine weight. Administration of DMBA was associated with significant increases in the incidences and numbers of tumors; this effect was augmented by E₂administration.

Conclusions: Based on the findings in this rat model, the hypothesis that E₂ may be effective in reducing anxiety and depressive behaviors and enhance sexual behavior in OVX rats, concurrent with trophic effects in the periphery, was supported. Moderate physiologic levels of E₂ might have beneficial effects on affective and sexual behaviors in female rodents, but regimens including E₂ might increase tumorigenic capacity.

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Citation Excerpt :
Sex hormones and their interaction with stress hormones play an important role in the development of stress-related disorders (Galea et al., 2014; Hillerer et al., 2019). Compelling evidence from various studies have demonstrated estrogen effects on anxiety and anxiety-like behaviors in both rodents and humans (Furuta et al., 2013; Pigott, 2003; Rapkin et al., 2002; Walf and Frye, 2007a, 2007b, 2009). In female rats, decreased anxiety-like behaviors are observed during pro-estrus when estrogen levels are high, and exogenous administration of estrogen shows anxiolytic effects on ovariectomized rats (Walf and Frye, 2007a, 2007b, 2009).
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Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model

Abstract

Eur J Obstet Gynecol Reprod Biol

Compr Psychiatry

Front Neuroendocrinol

Am J Obstet Gynecol

Am J Geriatr Psychiatry

Steroids

Neuropharmacology

Brain Res

Pharmacol Biochem Behav

Horm Behav

Lancet

Trends Pharmacol Sci

Physiol Behav

Behav Brain Res

Brain Res Rev

Brain Res

Deaths: Final data for 2004

Natl Vital Stat Rep

Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys

J Neurosci

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial

JAMA

The critical period hypothesis: Can it explain discrepancies in the oestrogen-cognition literature?

J Neuroendocrinol

Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The Women's Health Initiative Memory Study: A randomized controlled trial

JAMA

Estrogen and the risk of breast cancer [published correction appears in N Engl J Med. 2001;344:1804]

N Engl J Med

Epidemiology of susceptibility to breast cancer

Prog Clin Biol Res

Parity, age at first and last birth, and risk of breast cancer: A population-based study in Sweden

Breast Cancer Res Treat

Proportion of breast cancer cases in the United States explained by well-established risk factors

J Natl Cancer Inst

Age at first full-term pregnancy, lactation and parity and risk of breast cancer: A case-control study in Spain

Eur J Epidemiol

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

Br J Cancer

Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer

Ann Intern Med

Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women

J Natl Cancer Inst

A prospective study of endogenous estrogens and breast cancer in postmenopausal women

J Natl Cancer Inst

Breast cancer risk associated with gynecologic surgery and indications for such surgery

Int J Cancer