Transcript The strange case of female Hormone Replacement Therapy and

The strange case of female
Hormone Replacement Therapy
and Cognitive Salience
John Collier
Philosophy
University of KwaZulu-Natal
[email protected]
http://web.ncf.ca/collier
Outline of talk
1. Background on HRT (hormone replacement
therapy)
2. Female hormones (pre and post menopause)
3. Treatments
4. Con arguments concerning testosterone
5. Pro arguments concerning testosterone
6. Salience in epistemology (a connecting principle)
7. What went wrong (in terms of salience)
Background
• In the early 1980s Mary Williams, who axiomatized selection theory, told
me about the failure of doctors to include appropriate levels of
testosterone in post-menopause hormone replacement therapy despite
studies that showed that it a) maintained libido, and b) resulted in
improved feeling of well-being.
• On investigating recently I discovered that it is still not a standard
treatment, despite advocates in female aging and menopausal studies
literature and on respectable internet sites. The original research on mood
and libido improvement goes back to the 1960s.
• The reasons remain similar to those that Mary informed me of three
decades ago.
• Adverse effects are largely “unknown”, but speculation abounds.
• Despite this, testosterone replacement is becoming more common, but is
not yet usual in HRT. 2012 review paper argues on balance it is beneficial.
• This raises the question of why the resistance to this treatment for so
long, and why so many questions about benefits and safety remain un
answered. Especially since testosterone replacement in men is becoming
much more common very quickly.
Female testosterone 1
• On average, in adult males, levels of testosterone are
about 7–8 times as great as in adult females.
• As the metabolic consumption of testosterone in males
is greater, the daily production is about 20 times
greater in men.
• Females are also more sensitive to testosterone.
• Anabolic effects include growth of muscle mass and
strength, increased bone density and strength, and
stimulation of linear growth and bone maturation.
• Androgenic effects include after birth a deepening of
the voice, growth of the beard and axillary hair. These
happen in women with excessive androgens.
Female testosterone 2
• Androgens may modulate the physiology of vaginal tissue
and contribute to female genital sexual arousal.
• “Testosterone may prove to be an effective treatment in
female sexual arousal disorders.”
• There is no FDA approved androgen preparation for the
treatment of androgen insufficiency, however it has been
used off-label to treat low libido and sexual dysfunction in
older women, and less often other conditions. (1961)
• “Testosterone may be a treatment for postmenopausal
women as long as they are effectively estrogenized.”
Benefits are likely to be increased libido, better mood,
increased muscle mass and bone mass, and an increased
sense of well-being. It has also been used to slow
development of breast cancer, though evidence is sketchy.
Slowing of vaginal atrophy has been known since 1983.
Postmenopausal androgens
• Virtually none produced by ovaries after
menopause.
• Some produced by metabolism, especially from
DHEA-S (dehydroepiandrosteronesulphate).
• But overall levels drop quickly, and then more
slowly with age.
• Adverse effects of supplementation are thought
to be rise of lipid levels, insulin resistance,
hirsutism, lowered voice.
• Unsubstantiated fear of increased breast cancer,
cardiovascular disease, long-term safety (?).
Treatments
• Testosterone or methyltestosterone.
• Oral administration risks increased lipids, insulin
resistance. DHEA-S can be given orally.
• Ameliorated by transdermal administration
(usually patches).
• No appropriate dosage available for women.
• Not FDA approved in the US for women.
• Androgens can be converted in the body into
estrogens, so this must be considered in HRT.
• Literature tends to focus on sexual dysfunction.
Androgen therapy con
• May increase the risk of breast cancer.
• Not justified “merely” for raising libido.
• “Male hormone”, women feel better, better
cognitive function is artificial.
• Need for caution in current guidelines (compare
male androgen replacement)
• Difficult to measure androgens in women, slow
rather than sudden decline makes this a problem.
• No long term studies of risks
• “Androgen deficiency” not well-defined
Androgen therapy pro
• Licensed for use in Europe
• Minimal androgenic side effects documented –
heart disease, lipid increase, cancer (protective?)
• Produced naturally in women
• There is a sudden decline with menopause, but
even women in early 40s have half the circulating
testosterone of women in their 20s.
• Bone density, circulation and libido
improvements
• Mood improvement
Observations
• HRT with testosterone mostly focuses on increased libido,
though there are several other benefits like bone density,
better mood, increased muscle
• Literature tends to focus on possible but undocumented
problems
• Testosterone therapy seen as unnatural for women
• Increased libido and sexual function not seen as worth the
risks in women.
• Some evidence for increased cardiovascular risk in women
with reduced testosterone.
• Some evidence breast cancer risk is reduced.
• View as “male hormone”
• There are many popular myths, believed even by many
doctors
Salience
• Originally meant “to leap up” and still means this
in many contexts.
• Conspicuous, prominent
• In thinking, conspicuous, relevant; surprisingly
not supported in dictionaries, but for examples:
– Gather necessary information and salient facts before
making an important decision.
– The salient quality of them all is their sincerity and
directness.
– It's a salient feature of modern media that being
thought to be popular can make you more popular.
Hypothesis about the role of salience
in reasoning
• I propose that salience is a connecting
principle in reasoning implying relevance at
least and possibly support
• Clever people often rely (often reliably) on
salience to them as evidence
• Given a hypothesis, salient factors are taken as
support for the hypothesis
• This is a quick and dirty heuristic (often works
for smart people, but sometimes not)
Some properties of cognitive salience
• A species of attention based in habits (compare with
revisable “search patterns” for prey in birds)
• Not a very clear notion (objections to Lewis’s use, but see
Binmore, Samuelson)
• Requires philosophical clarification
• Typically unconscious or subconscious (“pops up”)
• Relative to experience and skill (epistemic virtue)
• But not fully determinate and can be rationally defeated
and modified
• David Armstrong anecdote: temporary failure to recognize
that being a feminist female lawyer is not more probable
than being a female lawyer
Salience in epistemology
• Epistemological theories appealing to salience:
– Virtue epistemology (salience as confirmation)
– Epistemic contextualism (salient defeaters)
• Conventions (salient alternatives -- Lewis)
• Emotionally laden situations are more likely to lead
one to rely on salience
• But this might mean only excitement or involvement
• However, it can also allow bias to enter, since things
one is emotionally involved with tend to be more
salient. Bias is not necessarily bad.
Hypothesis
The failure of doctors and the medical profession and
regulators to accommodate testosterone in
postmenopausal HRT is a consequence of the salience of
androgens as “male hormones”.
• Background bias of male model for medicine and
medical studies
• Bias that maleness is good (gender issues in general)
• Female libido devalued
• Focus on libido issues because sex is very salient
• Others?
Time for discussion!
John Collier
Philosophy
University of KwaZulu-Natal
[email protected]
http://web.ncf.ca/collier