The Multinational Postmarketing Observational Study of Women Prescribed Intrinsa
This is a prospective, controlled, non-interventional long-term cohort study of women who
are prescribed estrogen therapy or estrogen therapy in combination with Intrinsa®.
Intrinsa® is a transdermal patch that delivers 300 mcg of testosterone daily through the
skin of the abdomen, providing women with testosterone levels that are within the
physiological range for premenopausal women. It is indicated for the treatment of hypoactive
sexual desire disorder (HSDD) in women with bilateral oophorectomy and hysterectomy who are
receiving concomitant estrogen therapy.
A non-interference approach will be used to provide standardized, comprehensive, reliable
information on these treatments under routine medical conditions.
The two main objectives of this study are:
- to estimate the incidence of breast cancer, other gynecological cancer, myocardial
infarction, other cardiovascular outcomes and other rare serious adverse outcomes among
Intrinsa® users in actual clinical practice, and
- to compare these incidences with the incidences found in the comparison group of women
with bilateral oophorectomy and hysterectomy using estrogen therapy.
The primary variable for the statistical analysis is the breast cancer hazard ratio for
Intrinsa® users in comparison to users of estrogen therapy.
The secondary objectives of the study are:
- to analyze the Intrinsa® utilization pattern in a study population that is
representative for the users of this novel treatment
- to characterize the baseline risk of Intrinsa® users for breast cancer and
cardiovascular diseases and
- to investigate the reversibility of specific androgenic outcomes after stop of
The two study cohorts will consist of new users of Intrinsa® in combination with estrogen
therapy and estrogen therapy without simultaneous use of Intrinsa®, respectively. After
study entry cohort members will be followed for a period of five to eight years for rare
serious safety outcomes. Regular, active contacts with the cohort members by the ZEG study
team (=active surveillance) will provide the necessary information on health-related events
or changes in health status. All cohort members will be contacted at 6 and 12 months after
study entry, and then every 12 months.
Approximately 5.400 subjects per cohort will be recruited by participating physicians in
order to provide 50.000 women-years (WY) of observation, assuming a withdrawal rate of 10%
per year. Enrollment procedures should not interfere with the prescribing behavior of
physicians or with the individual needs of the participating women.
The study will be conducted in Italy, France, Spain, the UK and Germany. It could be
extended to other countries based on the international registration and launch status of
The study will be divided into two phases: a clinic phase, which includes an initial
consultation at baseline with a participating physician, and a follow-up phase, which
includes two follow-up contacts within the first year, and then annual follow-up contacts
for up to eight years post-baseline.
The study participants are women who have a new prescription of Intrinsa® in combination
with estrogen therapy or estrogen therapy respectively and who are willing to participate in
this cohort study. There are no specific medical inclusion or exclusion criteria other than
the guidance provided by the local product label. However, women who are not cooperative may
be excluded from study participation. Also women with a language barrier will not be
eligible for study inclusion.
This study will maintain scientific independence and will be governed by an independent
Advisory Council. The Center for Epidemiology and Health Research in Berlin, Germany and its
research team will be accountable for the Advisory Council (AC) in all scientific matters.
The members of the AC wil be international experts in relevant scientific fields (e. g.
epidemiology, gynecology and cardiology).
Information on the identity of the patients and treating physicians will be kept separated
from the clinical information throughout the study. All relevant national data protection
laws will be followed.
Observational Model: Cohort, Time Perspective: Prospective
gynecological cancer; serious cardiovascular diseases
Time to event analysis within 8 years
Klaas Heinemann, MD, PhD
Center for Epidemiology and Health Research, Germany
Sweden: Medical Products Agency