Gender-specific medicine involves the treatment of diseases in male and female reproductive systems separately, as well as in organs common to both genders considering their biological and social differences. Biological sex determination and differentiation are driven by the interaction of genetic and endocrinologic factors. Social factors also contribute to sexual differences in diseases. Both male and female bodies have breast tissues; however, hormones affect their differences in development, structure, and physiological changes and diseases. Estrogen stimulates epithelial proliferation and is associated with mammary gland lesions. In breast cancer, elevated expression of synthetase produces estrogen. Therefore, estrogen-dependent proliferation of breast cancer can occur in men and postmenopausal women. In benign mammary gland lesions, the estrogen level is higher than normal owing to reduction in metabolizing enzymes. Breast cancer is the most important disease requiring breast surgery and is the most predominant cancer among women. Breast cancer in men accounts for only 0.6% relative to the incidence rate in women. Among female mammary gland diseases, benign lesions such as fibroadenoma and mastopathy are rarely indicated for surgery. In contrast, when men present at outpatient departments with mammary gland disease, the diagnosis is almost always gynecomastia. We herein describe the characteristics of breast cancer and gynecomastia. Although female breast cancer research is constantly progressing, more studies in male breast cancer are warranted. New results are anticipated in gender-specific medicine.

Several women have been reported to have chronic respiratory disease. Symptoms such as cough and dyspnea markedly reduce the quality of life, and female patients tend to have mental stress. It is important to understand gender differences in respiratory diseases from the viewpoint of anatomical and physiological differences as well as psychosocial differences. Severe asthma, including phenotypes such as aspirin-intolerant asthma and obesity-related asthma, is reported to be more common in women. New therapeutic options such as biologics and bronchial thermoplasty are available. Chronic obstructive pulmonary disease (COPD) in women tends to be worse because of higher smoking susceptibility. Non-emphysematous type of COPD is common, and appropriate inhalation therapy is required. Among women with interstitial pneumonia, nonspecific interstitial pneumonia caused by collagen disease is common, and corticosteroid and immunosuppressant therapy should be considered. In addition, non-smoker's lung cancer and adenocarcinoma positive for EGFR gene mutation are common among women. Because molecular targeted drugs are effective, precise diagnosis is needed at the gene level. The incidence of pulmonary non-tuberculous mycobacteriosis with nodular bronchiectasis has been increasing in middle-aged and elderly women, but treatment options are limited. Pulmonary lymphangiomyomatosis and catamenial pneumothorax are rare diseases that occur only in women. Recently, rapid advancement has been noted in the treatment of respiratory diseases. The perspective of gender difference is associated with personalized medicine and paves a new path for respiratory medicine.

Gender medicine (GM) deals with the effects of sex and gender differences between males and females. Since 2007, Tokyo Women's Medical University has operated the nation's largest Women-Specific Clinic based on GM, at which 13 female specialists in various fields collaborate. We perform differential diagnoses of complaints while considering gender and sex differences in the mind and in diseases, life stage, and social background. We analyzed the clinical data of 285 patients who visited us during the first year, 68% (195/285) of whom presented with undefined complaints that included menopausal symptoms, and 26.7% (52/195) of whom were found to have organ diseases which explained the undefined complaints after our differential diagnosis. Forty-three of 195 women had endocrine diseases and 29 of them had thyroid dysfunctions; the most frequent endocrine disease. In other words, the frequency of endocrine diseases among patients who were considered to have undefined complaints were 22% and the corresponding frequency of thyroid dysfunction was 15%. In particular, thyroid dysfunction symptoms overlapped with menopausal symptoms and were difficult to distinguish without thyroid function tests. However, the endocrine test is not included in the general test, which increased the difficulty in detecting endocrine diseases. We need to be aware that women generally have a higher incidence of endocrine disease than men and that some endocrine diseases occur during pregnancy, postpartum, or around menopause. Incorporating GM aspects into daily practices can improve the accuracy of the diagnosis overall, especially the diagnosis of endocrine diseases in women.

Differences in cardiovascular disease are found between the genders. In women, it is known that estrogen has both indirect and direct protective effects on the cardiovascular system. This includes a decrease in low-density lipoprotein cholesterol (LDL-C), an increase in high-density lipoprotein cholesterol (HDL-C), the vasodilatation response by endothelial Nitric Oxide Synthase (eNOS) synthase, and prostacyclin synthesis.

Many cases of coronary spastic angina and acute coronary syndrome (ACS) have been observed during the menstrual and the late luteal phases of the menstrual cycle, corresponding with low levels of estrogen. After menopause, the risk of atherosclerosis and associated conditions such as; dyslipidemia, hypertension, obesity, diabetes, T cell activation, and adhesion molecules, increase. Consequently, the risk of a cardiovascular event also increases. In addition, regarding the pathological mechanism underlying ACS, erosion is observed most prominently during pre-menopause, whereas plaque rupture is observed in post-menopause.

Furthermore, microvascular angina is often found in menopausal women displaying various symptoms, thus a diagnosis may be difficult. We recognize a decrease in vascular endothelial function and the coronary flow reserve and a high level of lactic acid in the coronary sinus as diagnostic criteria. Regarding problems associated with the "super-aging" society, there are many elderly female patients with HFpEF (heart failure with preserved ejection fraction) who have diastolic dysfunction. Also well-known are cases of atherosclerosis and osteoporosis progressed by common risk factors, and recently, vascular bone disease.

There are characteristics in women for microvascular angina and heart failure, as well as ischemic heart disease, due to atherosclerosis caused by the sex hormone environment in later life stages. Considering gender-specific medicine in the prevention and treatment of cardiovascular disease is important for healthy aging of women.

Here we present dermatological diseases and symptoms with a focus on women. The diseases and symptoms are divided into the following 3 groups, and we focus mainly on the first: 1) skin diseases/symptoms found more commonly in women, 2) diseases with increased prevalence due to traditional lifestyles of mothers, and 3) non-life-threatening diseases associated with the natural aging process.

The paper explains the skin symptoms and characteristics of collagen diseases which are extremely common in women. Specifically, it looks at 3 systemic diseases whose early diagnosis requires examination by a dermatologist: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM). In order to accurately diagnose a patient, healthcare professionals must recognize specific skin symptoms and understand which diseases they signify. For example, butterfly rashes and intractable pernio-like eruptions are indicative of SLE, Raynaud's phenomenon and nail fold bleeding are initial symptoms of SSc, and facial erythema is an early symptom of DM.

Next, this paper outlines the symptoms and treatment of hand eczema, and the importance of addressing the relationship between traditional gender roles and their prevalence.

Finally, this paper recognizes that women are increasingly seeking treatment for aging-related skin diseases such as senile pigment freckles, verruca senilis, and diffuse alopecia. We then suggest strategies for meeting the needs of these patients.

In recent years, the number of patients with neuro-immunological diseases, such as multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorder (NMOSD), and myasthenia gravis (MG), has been increasing in Japan. These diseases are commonly seen in women of childbearing age. Therefore, pregnancy and delivery are major issues in patients with these diseases. Pre-conception care and management of medication during pregnancy, resumption after delivery, breastfeeding, and effects on the mother and fetus are all very important issues.

In pregnancy in MS, the current guidelines focus on the use of disease-modifying drugs (DMDs) throughout pregnancy. The appropriate DMD prevents relapses for three months postpartum.

The annual recurrence rate after delivery was much higher for NMO・NMOSD than for MS. In addition, pregnancy after NMOSD onset is a risk factor for miscarriage, and pregnancies with high disease activity may be at increased risk of miscarriage.

Exacerbations of MG occur in approximately 41% of pregnancies, with remission in 29% and no change in 30%. Exacerbations occur in the first trimester and the three months postpartum. What is common in these autoimmune neurological diseases is that continuing appropriate treatment and stabilizing disease activity can prevent postpartum recurrence.