Environment, human reproduction, menopause, and andropause.

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS

Personalized Dual-Hormone Control for Type 1 Diabetes Using Deep Reinforcement Learning

We introduce a dual-hormone control algorithm for people with Type 1 Diabetes (T1D) which uses deep reinforcement learning (RL). Specifically, double dilated recurrent neural networks are used to learn the control strategy, trained by a variant of Q-learning. The inputs to the model include the real-time sensed glucose and meal carbohydrate content, and the outputs are the actions necessary to deliver dual-hormone (basal insulin and glucagon) control. Without prior knowledge of the glucose-insulin metabolism, we develop a data-driven model using the UVA/Padova Simulator. We first pre-train a generalized model using long-term exploration in an environment with average T1D subject parameters provided by the simulator, then adopt importance sampling to train personalized models for each individual. In-silico, the proposed algorithm largely reduces adverse glycemic events, and achieves time in range, i.e., the percentage of normoglycemia, 93% for the adults and 83% for the adolescents, which outperforms previous approaches significantly. These results indicate that deep RL has great potential to improve the treatment of chronic diseases such as diabetes