Prof. Alexander Rübig, MD, PhD

Professor of Obstetrics & Gynecology

Abstract | CV

Abstract

New Perspectives in Hormonal Therapy

A. Rübig 
Schering AG, Strategic Business Unit Gynecology & Andrology,
Sellerstrasse 31, D - 13342 Berlin, Germany

Drospirenone (DRSP) is a novel progestogen which differs from others, in that it is derived from 17a-Spirolactone. The pharmacodynamic profile in terms of clinical relevance is more closely related to endogenous progesterone than any other currently available synthetic progestin. DRSP displaces progestational, antimineralcorticoid and antiandrogenic activity but is devoid of estrogenic, androgenic, glucocorticoid, antiglucocorticoid and mineralcorticoid activity. The affinity to the mineralocorticoid receptor makes DRSP act as an Aldosterone-Receptor-Antagonist. Anti-aldosterone activity plays an important role via the RAAS (Renin-Angiotensin-Aldosterone-System) in the kidney, but additionally has some pharmacodynamic activity on the heart and the vessels, contributing to a cardiovascular interplay on several levels.

DRSP has been developed, in combination with 1 mg 17ß-estradiol, by Schering AG as continuous-combined HRT product, containing either 1, 2 or 3 mg DRSP. Clinical efficacy and safety of the E2/DRSP products has been investigated in several phase II/III studies, contributing to knowledge of clinical relevance of this novel and unique HRT combination.

The clinical studies proved efficacy of all three E2/DRSP combinations on relief of hot flushes and related climacteric symptoms as well as on prevention of postmenopausal osteoporosis. As can be expected from a continuous-combined HRT product nowadays, the return to amenorrhea after treatment start is above 80% within a year.

With respect to safety, clinical studies proved endometrial protection for all three E2/DRSP combinations within one and two years of treatment. No case of hyperplasia or cancer appeared in any of these treatment arms.
The combinations of E2/DRSP showed favorable lipid profiles, not attenuating the beneficial estradiol effects, probably due to lack of androgenicity of DRSP. Due to the unique antimineralocorticoid property of DRSP, women receiving the combination of E2/DRSP did not show increases, but decreases in total body weight. The AE/SAE profile does not differ from usual HRT patterns.

The combination of a natural estradiol and a progestogen with anti-aldosterone properties offers new dimensions in cardivascular activity and benefits. Several positive effects of Aldosterone-Receptor-Antagonism on different target parameters of cardiovascular impact are already known for quite long time resulting mostly - but not only - from animal studies. To evaluate the benfit of a combination of E2/DRSP for postmenopausal women, blood pressure data were collected throughout nearly all phase III studies on this preparations. 

The blood pressure lowering effect of E2/DRSP - partly due to the anti-aldosterone activity of DRSP - was proven to be more pronounced in combinations with higher drospirenone dosages and has a beneficial treatment effect especially in mild hypertensive women. Due to the combination of estradiol with the unique progesterone DRSP, the well known favorable effects of estradiol on blood pressure were not attenuated at any dose of DRSP. 

Further studies on investigation of the combination of E2/DRSP in cardiovascular effects are underway or planned due to the immense impact of cardiovascular morbidity and mortality for women and the society.

In conclusion, the unique combination of 1 mg 17ß-estradiol with DRSP at different dosages as continuous-combined HRT product is safe and effective in conventional terms of treatment. Moreover the anti-aldosterone and antiandrogenic properties of DRSP offer new dimensions on the cardiovascular system as added benefits which no other HRT product up to now is able to offer.

CV

Before attending Medical School Alexander Rübig served in the German Navy and completed the officer´s training. He graduated from the Universities of Mainz and Münster in 1979 and gained his doctoral degree in the same year from Westfälische-Wilhelms-University in Münster. He pursued his interest in obstetrics and gynecology, undergoing specialty training in these disciplines and in surgery. Between 1984 and 1992, he worked as a Senior Registrar and Senior Consultant in obstetrics and gynecology at several large (university)- hospitals in Germany. In 1995, he was awarded full registration as a Medical Practitioner (Spec. Reg.: OB/GYN) in the UK. In 1998 he was promoted to Navy Captain (MC GENR) and appointed Reserve Commanding Officer of the German Armed Forces Hospital in Berlin. In 1998, he was awarded a Professorship of Obstetrics & Gynecology at the State University of Oviedo, Spain. Professor Rübig’s particular interests are gynecological and obstetric ultrasonography, prenatal diagnosis and therapy, and gynecological endocrinology. From 1997, he was appointed Head of Clinical Development at Schering AG, Berlin, and since 2001 has filled the role of Head of Corporate Strategic Marketing for the same company.