The strange case of female Hormone Replacement Therapy and Cognitive Salience John Collier Philosophy University of KwaZulu-Natal

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 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