Steroid Hormone Action In Female Reproduction

Nieman, Lynnette

Abstract

This project focuses on leiomyomata (fibroids) and examines factors related to their pathogenesis, diagnosis and/or potential treatment. Ongoing work seeks to evaluate the utility of the progesterone response modulator CDB2914 as a treatment of fibroids. We previously investigated the effect of single doses of the agent on the menstrual cycle in women, and showed that doses of 100 or 200 mg retard folliculogenesis and precipitate menses, in the follicular and luteal phase respectively. Two randomized double-blind placebo-controlled clinical trials from our group showed reduction in fibroid size in women receiving CDB 2914 at a daily dose of 10 or 20 mg for three months, as compared to women receiving placebo. One of these studies showed continued efficacy during a second three-month study. We also are using gene arrays to evaluate the pathophysiology of leiomyomata.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAHD000637-18
• Application #: 8351111
• Support Year: 18
• Fiscal Year: 2011
• Total Cost: $752,654

Institution

• Name: Eunice Kennedy Shriver National Institute of Child Health & Human Development

Publications

Martinez, Pedro E; Rubinow, David R; Nieman, Lynnette K et al. (2016) 5?-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder. Neuropsychopharmacology 41:1093-102

Schmidt, Peter J; Ben Dor, Rivka; Martinez, Pedro E et al. (2015) Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal Depression: A Randomized Clinical Trial. JAMA Psychiatry 72:714-26

Lewis, Erin I; Chason, Rebecca J; DeCherney, Alan H et al. (2013) Novel hormone treatment of benign metastasizing leiomyoma: an analysis of five cases and literature review. Fertil Steril 99:2017-24

Lee, Ellen E; Nieman, Lynnette K; Martinez, Pedro E et al. (2012) ACTH and cortisol response to Dex/CRH testing in women with and without premenstrual dysphoria during GnRH agonist-induced hypogonadism and ovarian steroid replacement. J Clin Endocrinol Metab 97:1887-96

Nieman, Lynnette K; Blocker, Wendy; Nansel, Tonja et al. (2011) Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study. Fertil Steril 95:767-72.e1-2

Smith, Kathryn; Alnifaidy, Redab; Wei, Qingxiang et al. (2011) Endometrial Indian hedgehog expression is decreased in women with endometriosis. Fertil Steril 95:2738-41.e1-3

Stratton, Pamela; Levens, Eric D; Hartog, Beth et al. (2010) Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914. Fertil Steril 93:2035-41

McCarthy-Keith, Desireé; Nurudeen, Sahadat; Armstrong, Alicia et al. (2010) Recruitment and retention of women for clinical leiomyoma trials. Contemp Clin Trials 31:44-8

Levens, Eric D; Wesley, Robert; Premkumar, Ahalya et al. (2009) Magnetic resonance imaging and transvaginal ultrasound for determining fibroid burden: implications for research and clinical care. Am J Obstet Gynecol 200:537.e1-7

Stegmann, Barbara J; Funk, Michele Jonsson; Sinaii, Ninet et al. (2009) A logistic model for the prediction of endometriosis. Fertil Steril 91:51-5