Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone‐related clinical disorders

Abstract

DL-Centchroman (67/20; INN: Ormeloxifene) synthesized at the Central Drug Research Institute, Lucknow, is a nonsteroidal once-a-week oral contraceptive. It was introduced in Delhi in July, 1991, marketed in India in 1992 as Saheli and Choice-7 (Hindustan Latex Ltd., Thiruvananthapuram) and Centron (Torrent Pharmaceuticals India Ltd., Ahmedabad), and included in the National Family Welfare Programme in 1995.5 According to post-marketing surveillance, approximately 100,000 women were using this pill and approximately 1100,000 menstrual cycles were covered until 1996. It is a unique need-oriented contraceptive being effective when taken immediately after coitus or routinely as a weekly pill and has the advantage of less frequent administration. Its contraceptive action is quickly reversible. It has long terminal serum halflife of 168 hr in women and exhibits duration of anti-implantation/estrogen antagonistic action of 120 hr, despite a short (24.1 hr) serum halflife, in the rat. In lactating women, it is excreted in milk in quantities considered unlikely to cause any deleterious effect on suckling babies. In phase II and III multicentric trials as a contraceptive, children born of method-and-user failure pregnancies showed normal milestones, without any congenital anomaly. Reports of its promising action in the management of certain hormone-related clinical disorders are available. It has an excellent therapeutic index and is considered safe for chronic administration.

Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer

“…Recent studies suggested that ORM may be effective in inhibiting breast cancer, head and neck cancer, and chronic myeloid leukemia cells (18). Moreover, ORM is reported to have an excellent therapeutic index and is safe for chronic administration (19). This study demonstrates the inhibitory role of ORM on the SHH signaling pathway, and describes inhibitory patterns of this drug on pancreatic tumor progression using bidirectional tumor stromal interactions.…”

Ormeloxifene Suppresses Prostate Tumor Growth and Metastatic Phenotypes via Inhibition of Oncogenic β-catenin Signaling and EMT Progression

“…ORM has an excellent therapeutic index and is safe for chronic administration in humans (14). The maximum serum concentration (C max ) of ORM in humans is dose-dependent (C max of 55.53 ± 15.43 ng/ml for 30 mg dose and C max of 122.57 ± 6.25 ng/ml for 60 mg dose) and is reached within 4–6 hrs(41).…”

“…Herein, we have shown that ORM effectively inhibits molecular signatures of EMT, β-catenin/TCF-4 transcriptional activity, and induces phosphorylation of GSK3β, and degrades β-catenin leading to the suppression of prostate tumor growth in xenograft mouse model. Since, ORM is reported to have an excellent therapeutic index and is safe for human use for anti-fertility (contraception) purpose (14), ORM appears to be an ideal pharmacological agent for its repurposing as an anti-cancer agent against metastatic PrCa.…”

Centchroman Regress Mastalgia and Fibroadenoma: An Institutional Study

“…It is devoid of progesterone, androgenic and antiandrogenic activities. [14] Centchroman is free from adverse effects like nausea, vomiting, weight gain and dizziness. Centchroman does not disturb ovulation as it does not delay return of fertility (after stopping).…”