Sex affects health: women are different than men Osteoporosis Different patterns of Melanoma occurrence Autoimmune conditions Body composition & metabolism

Sex affects health Males & females have different patterns of illness Diseases other than those of the reproductive system affect both sexes, often with different frequencies or presentations – or they may require different treatments

I. Osteoporosis Osteoporosis – Results when the rate of bone resorption outstrips the rate of bone formation 35% of all women >65 years old have osteoporosis (15% of all Caucasian women)

Normal bone: T-score better than -1. Osteopenia: T-score between -1 and -2.5 Osteoporosis: T-score less than -2.5

Factors that contribute to bone health Dietary Calcium & Vitamin D required for bone formation Premenopausal women should obtain 1,000 mg/day Postmenopausal women – 1,200 to 1,500 mg/day Estrogen & testosterone critical for maintenance of peak bone mass Weight bearing exercise creates strong bone structure Smoking weakens the bone structure Certain drugs ( e.g. Corticosteroids) promote bone loss

II. Different patterns of Melanoma occurrence non-melanoma = Melanoma – Incidence higher among women, however mortality higher among men Cause – Risk factors –

Early detection is critical!!!

III. Autoimmune conditions The adaptive immune response Activation of the complement and coagulation systems plasma activity level of phospholipase A2, a key enzyme in causing chronic inflammatory diseases, is significantly higher in Caucasian women than their male counterparts Interleukin-1-receptor-II (reduces the inflammatory response), is present in higher concentration in men than women

A. Autoimmune disease May be localized or ubiquitous Difficult to identify leading causes, difficult to diagnose May be associated with infectious agents (virus, bacteria) Hypothesized that "molecular mimicry” may be occurring- epitopes of the microorganism closely resemble self-antigens "bystander effect" microorganisms expose self-antigens to the immune system by directly damaging tissues during an active infection Many autoimmune disease are highly predominant in females, most during their child-bearing years “ Systemic and organ-specific autoimmune diseases, (e.g. rheumatoid arthritis, myocarditis) are the leading cause of death in women >65 years of age

Infections occur before the onset of symptoms of autoimmune disease, making links to specific causative agents difficult. When a person is first infected (day 0), usually no symptoms are apparent. Signs and symptoms of autoimmune disease are clearly present and easily confirmed by physicians during the chronic stage of autoimmunity. However, the infection has been cleared by this time, making it difficult to establish that an infection caused the autoimmune disease (from Fairweather & Rose, 2004)

Some common autoimmune diseases: Hashimoto’s thyroiditis (underactive thyroid) Tiredness, depression sensitivity to cold, muscle weakness and cramps weight gain, dry hair, tough skin constipation Graves’ disease (overactive thyroid) Insomnia, irritability, weight loss, heat sensitivity, fine brittle hair weakness in your muscles, shaky hands Lupus swelling and damage to the joints, skin, kidneys, heart, lungs, blood vessels, and brain rashes on parts of the body Multiple sclerosis (MS) weakness and trouble with coordination, balance, speaking, and walking tremors numbness and tingling feeling in arms, legs, hands, and feet Rheumatoid arthritis inflammation of the joints muscle pain, weakness, fatigue Symptoms of autoimmune diseases can come and go, and severity can vary

~6.7 million women affected by autoimmune disease

B. Why are these autoimmune diseases affecting more females than males? Genetics? AD tend to cluster in families and in individuals which suggests that common mechanisms are involved in disease susceptibility However, twins studies indicate that genetic as well as environmental factors are necessary Hormones? Variety of sex hormone receptors found on immune cells & cytokine receptors have likewise been discovered on hormone-producing tissues, which suggests bidirectional regulation of the immune response Proinflammatory cytokines stimulate the release of glucocorticoids from the hypothalamus-pituitary-adrenal axis, which regulates the inflammatory process, along with androgens and estrogen Recent study found that Estrogen amplifies the immune response to coxsackievirus B3 in mice, increasing TNF-α and IL-4 levels Different environmental exposure than men?

IV. Body composition & metabolism Body fat – Hormonal changes may increase a female’s appetite Menopause is associated with a shift toward more fat + deposition of fat in abdominal region Different energy requirements due to different body size, composition and activity levels –