7.4
Pharmaceuticals and women
See Background Chapter 7.4
Although women are the most frequent users of medicines, little is known about many
aspects of women’s interaction with medicines and there are research gaps on
important ‘female’ health issues, including breast cancer, reproduction control, female
subfertility, pregnancy and lactation, and menopausal conditions (including hormone
therapy). Several studies have shown that there may be differences in the effects of
medicines in women and men. 1 , 2 Measuring the pharmacokinetics of medicines in
women of different ages and body weight would provide much-needed information
for prescribers.
Since the 1960s, millions of women have taken hormonal contraception either orally
(“the pill”), by injection (as a depot preparation) or as an implant. The rate of use varies
by geographical area and by age.3 Nearly 40% of women who take oral contraceptives
do so for more than five years. Following safety concerns about the use of such
medicines for long periods, the hormonal content has been reduced over time to
improve safety while at the same time preventing pregnancy. The impact of hormonal
fertility control has been dramatic, with declines in fertility occurring in nearly all
countries. This has had a substantial impact on the age structure of populations. While
most women have access to hormonal contraception, uptake varies greatly, with rates
as low as 2% in Cameroon.4
As women increasingly get married at older ages and defer having children, the
prevalence of female subfertility has increased. However, subfertility treatment is still
sub-optimal. The success rate of IVF is about 25% per cycle and the technique is
associated with side-effects and an increase in the risk of complications and multiple
births. Multiple births are associated with an increase in morbidity, mortality and
disability.
An additional concern is the lack of knowledge about the effects of medicines during
pregnancy. Since the thalidomide crisis in the early 1960s, concern remains about the
use of medicines in pregnancy.5 It is estimated that about 62%-80% of pregnant women
take at least one medicine during pregnancy. Although women reduce the use of
medicines once they know they are pregnant, there is a risk of exposure in the period
between conception and the detection of pregnancy. Meanwhile, as more women take
medicines for chronic conditions, it becomes inevitable that women will take medicines
during pregnancy and while lactating. For most medicines, there are no certainties
about their possible effects on the developing foetus or nearly born child. Since hardly
any medication today is tested in humans in pregnancy or during lactation, this leads
to the use of unproven, off-label medicines at these times. There is a continuing need to
collect data on all possible exposures and outcomes and to analyse this information.
The use of post-reproductive hormone replacement therapy (HRT), which varies from
0% to 42% among women in 20 countries,18 entails both risks and benefits. While longterm HRT use has been found to be associated with prevention of chronic diseases
(osteoporosis, some cancers), the use of HRT may also increase the risks of several
cancers and cardiovascular disease.
A large part of the problems associated with female interactions with medicines is due
to a lack of basic knowledge about the effects of hormones, changing physiology in
pregnancy or during lactation, and the causes of subfertility. In the past, women's
health has often been neglected. For a long time, women were excluded from clinical
trials — partly due to ethical considerations but also because it was suggested that
research involving women had practical difficulties because of reproduction and the
hormonal cycle. Over the past decade, in response to demands to include more women
in clinical trials, the policy of the regulatory agencies towards their inclusion has
changed. Both the EMEA and FDA have developed guidelines which encourage the
participation of women in clinical trials.6,7 Such trials need to involve all phases of
clinical trials including Phase 1 dosing studies. Very recently, guidelines which
improve post-marketing research in pregnant women have been developed.
In summary, gaps in knowledge and research on women and pharmaceuticals include:

Although many conditions affect one gender more than the other (e.g., lupus,
breast cancer, multiple sclerosis) women are still frequently excluded from
clinical trials and other types of medical research because of practical issues
related to reproduction and hormone cycles.

Many female medicine therapies are long-term and require appropriate risk
management systems for long-term use of medicines.

Although the use of medication in pregnancy has been a safety concern for
many decades, this area is still underfunded. There has been little investment in
efforts to collect data at an international level on birth defects and susceptible
exposures, methodology and classification systems.
There remains a need for publicly-funded research on reproduction control, subfertility,
pregnancy and lactation (including birth defects), and the use of post-reproduction
hormones. The individual research programmes will vary according to the specific
problem. For reproduction control and subfertility, basic and clinical research will
probably be the priorities. For pregnancy and lactation (including birth defects), the
creation and analysis of exposure and defect registers using pharmaco-epidemiological
approaches are likely to be the methods of choice.
1
Dominick KL, Ahern FM, Gold CH, Heller DA. Gender differences in NSAID use
among older adults with osteoarthritis. Ann Pharmacother 2003;37(11):1566-1571.
2
Isacson D, Bingefors K. Epidemiology of analgesic use: a gender perspective.
Eur J Anaesthesiol Suppl 2002;26:5-15.
3
Lundberg V, Tolonen H, Stegmayr B, Kuulasmaa K, Asplund K, WHO MONICA
Project. Use of oral contraceptives and hormone replacement therapy in the WHO
MONICA project. Maturitas 2004;48(1):39-49.
4
World fertility report 2003. New York: United Nations, Department of Economic and
Social Affairs, Population Division; 2004. Report No.: ESA/P/WP.189.
5
Diggle GE. Thalidomide: 40 years on. Int J Clin Pract 2001;55(9):627-631.
6
General considerations for clinical trials. London: The European Agency for the
Evaluation of Medicinal Products (EMEA); 1997. Report No.: CPMP/ICH/291/95.
7
Milestones in women's health. Rockville (USA): Food and Drug Administration; 2001.
Available from: http://www.fda.gov/womens/milesbro.html (accessed 8 July 2004).