**7. Acknowledgement**

As a faculty member of the Child Psychopharmacology Institute and as a consultant for Avanir Pharmaceuticals I wish to express my gratitude to my colleagues Randall Kaye, M.D., MPH, R. Dennis Staton, Ph.D., M.D. and Scott Siegert, Pharm.D. for their collegial support and expertise.

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**15** 

*1Romania 2France* 

Adela Voican et al.\*

**Pharmacology of Hormone** 

*1Universitatea de Medicina din Craiova (AV,LN),* 

**Replacement Therapy in Menopause** 

*2Univ Paris-Sud, Faculté de Médecine Paris-Sud UMR-S693, Le Kremlin Bicêtre,* 

Menopause represents the final stage of the continuous process of reproductive aging in a woman's life, marking the end of her fertility. According to the World Health Organization (WHO), the natural menopause is defined *as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity* (WHO Report, 1996). Preceded by endocrine and menstrual cycle changes described as "menopausal transition", natural menopause occurs at an average age of approximately 51 years, although a high inter-individual variability is supported by results from epidemiological studies. However, occurrence of menopause outside the estimated normal age interval (45-55 years) is associated with increased morbidity, either when a late or on the contrary, a premature cessation of menstruation appears. A late menopause implies a longer exposure to estrogens and a possible increased risk for breast (Colditz, 1993; Kelsey & Bernstein, 1996) and endometrial cancer (Dossus et al., 2010; McPherson et al., 1996) or for venous thromboembolism (Simon et al., 2006). On the other hand, women entering menopause earlier are facing a hypo-estrogenic state for a longer period compared to women undergoing normal menopause. That is the case for about 1% of women, which are confronted with the diagnosis of primary ovarian insufficiency (POI). POI is defined by the presence of amenorrhea associated with elevated follicle-stimulating hormone (FSH) levels in the menopausal range in women younger than 40 years (Bachelot et al., 2009). Women facing a premature cessation of the ovarian function were shown to be at increased risk for premature death, cardiovascular disease, neurologic disease, mood disorders, osteoporosis or psychosexual dysfunction (Shuster et al., 2010). As the main rationale for these disorders was linked to hormonal changes, maintaining a certain level of ovarian steroids for a given period of time arose as an essential condition for conserving life quality in women (Wilson, [1966]). Accentuated by the increasing life span, researches related to menopause and its treatment have provided scientific community with an increased body of data during the last decades. However, different aspects regarding the benefit/risk balance or the ideal doses and routes of administration of hormone replacement therapy (HRT) in

menopausal women remain uncertain (Grodstein et al., 1997; Rossouw et al., 2002).

 Bruno Francou, Liliana Novac, Nathalie Chabbert-Buffet, Marianne Canonico, Geri Meduri, Marc Lombes, Pierre-Yves Scarabin, Jacques Young, Anne Guiochon-Mantel and Jérôme Bouligand

**1. Introduction** 

 \*

*Univ Paris-Sud, France* 

Yagasaki Y, Numakawa T, Kumamaru E, Hayashi T, Su TP, Kunugi H. "Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release." *J Biol Chem.*, 2006: May 5;281(18):12941-9.
