The Effect of Estrogen Receptor Modulator (Raloxifene) on Endometrioma Cells in Culture

Short Communication

Austin J Reprod Med Infertil. 2015;2(3): 1018.

The Effect of Estrogen Receptor Modulator (Raloxifene) on Endometrioma Cells in Culture

Laura Spector DO, Lydia Kaufman BS and Badawy SZA*

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, State University of New York, Upstate Medical University, Syracuse, New York, USA

*Corresponding author: Shawky ZA Badawy, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, State University of New York Upstate Medical University, Syracuse, Syracuse, NY 13224, New York, USA

Received: June 01, 2015; Accepted: June 21, 2015; Published: June 29, 2015


Objective: To study the effect of raloxifene on endometrioma cells in culture.

Methods: Three cell lines were developed from endometriomas removed surgically. These were treated with Raloxifene in a concentration of 200 micrograms/milliliter of culture medium. Control cell lines received culture medium only.

Results: Raloxifene caused significant suppression of endometrioma cells in culture as compared to controls.

Conclusion: The results of this research suggest that Raloxifene acts directly on endometrioma cells, an estrogen antagonist, thus inhibiting growth of these cells.

Keywords: Endometrioma Cells; Raloxifene; Estrogen antagonist; Raloxifene


Raloxifene is a Selective Estrogen Receptor Modulator (SERM). SERMs are competitive inhibitors of estrogen binding to estrogen receptors [1]. They act by attaching themselves to the estrogen receptors, and their effect could be either an antagonist or agonist effect, depending on the tissue. Raloxifene has been approved by the FDA for the treatment of osteopenia and osteoporosis [2,3,4,5]. It is known to have an estrogen antagonist effect on the breast tissue and the endometrial tissue and an estrogen agonist effect on the bone, lipids, brain and liver [2].

Raloxifene is a polyhydroxylated nonsteroidal compound with a benzothiophene core that binds with high affinity to both estrogen receptor α and estrogen receptor β. It is absorbed rapidly after oral administration (bioavailability ~2%). The half-life of Raloxifene is approximately 27 hours and it is eliminated primarily in the colon [6].

Conflicting data exists regarding the effect of Raloxifene on the endometrium. While studies performed in humans in vivo indicate a neutral or non-agonist effect on the endometrium, an experimental study conducted on ovariectomized mice demonstrated an agonist effect on the endometrium. The conflicting data may be due to the estrogen status of the subjects. It has been implicated that a mild agonist effect is present with significantly nonestrogenized females [7,8].

Raloxifene has been shown to have an estrogen antagonist effect on the endometrium. Sonogram and endometrial biopsy studies in postmenopausal women with osteoporosis treated with Raloxifene have shown absence of any stimulatory effect, and the endometrium remained atrophic. Studies that compared Raloxifene and Tamoxifene on the endometrium demonstrated occurrence of endometrial cancer in the latter [9].

The atrophic changes in the endometrium after Raloxifene use encouraged us to evaluate its effects on endometriosis tissue. The present study attempts to demonstrate the inhibitory effect of Raloxifene on endometrioma cells in culture.

Materials and Methods

This study was approved by the Institutional Review Board of SUNY Upstate Medical University and Crouse Hospitals. Patients entered in the study signed a consent form. During the surgery, the endometrioma was removed and an approximately 1cm piece of the endometrioma tissue was placed in a culture medium tube on ice and sent to our research laboratory. The rest of the tissue was sent to surgical pathology for evaluation.

Endometrioma tissue, from IRB consented patients, were then grown in Medium 199 (Mediatech) with 10% Fetal Bovine serum (FBS, Hyclone) and an antibiotic/antimycotic solution (Hyclone). The cell lines developed were used in our study. All cells were used at passage #1 or #2 and grown in sterile 12-well cell culture plates (Corning, Costar) coated with fibronectin-like protein polymer plus (Sigma-Aldrich) [10]. Three cell lines were used in this study (1507, 4655A, MH1129).

The Experimental media containing 200ug/mL of Raloxifene (EVISTA, Lilly) was placed on the wells at the beginning of the cells exponential growth phase (when the cells were most metabolically active), to test the effect of Raloxifene on endometrioma cells in culture. Cells were lifted with trypsin-EDTA (Mediatech) and viable cells were counted by hemocytometer in 50% Trypan blue exclusion dye (Mediatech).

Control wells and Raloxifene treated wells were counted at 0, 72 and 96 hours. The number of cells was then compared for analysis.

Statistical analysis comparing effects of Raloxifene as compared to controls used the Student T-test where significance is less than 0.05.


The control endometrioma cells continued their growth for the duration of the experimental study. The cells treated with Raloxifene showed inhibition of their growth with statistical significance at 96 hours (Figure 1, 2, 3, 4).