During the menstrual cycle, estradiol-17β and progesterone experience fluctuations. These hormones have various effects on both reproductive and nonreproductive systems. They profoundly impact the ovary, oviduct, uterus, cervix, vagina, external genitalia, hypothalamus, and pituitary. In addition to reproductive tissues, estrogen and progesterone play crucial roles in nonreproductive tissues. For instance, estrogen is essential for the closure of long bone epiphyseal plates in both males and females. It exerts a bone anabolic and calciotropic effect and enhances intestinal calcium absorption. Furthermore, estrogen regulates the function of osteoblasts and osteoclasts, promoting bone formation over resorption. Reduced estrogen levels during menopause contribute to bone loss and osteoporosis.

Estrogen also influences the liver by improving lipoprotein profiles in the circulation. It enhances the expression of the LDL receptor, facilitating the clearance of cholesterol-rich LDL particles by the liver. Moreover, estrogen increases the levels of HDL and regulates the production of various transport proteins, including cortisol-binding protein, thyroid hormone–binding protein, and SHBG.

Regarding cardiovascular organs, premenopausal women exhibit lower incidences of cardiovascular disease compared to men and post-menopausal women. Estrogen promotes vasodilation by increasing the production of nitric oxide, which relaxes vascular smooth muscle and inhibits platelet activation. Specific variations in the estrogen receptor have been associated with an increased risk of cardiovascular disease.

Estrogen and progesterone are also involved in maintaining healthy skin. They contribute to the normal thickness of the epidermis and dermis, stimulate the proliferation of keratinocytes, and inhibit their apoptosis. In the dermis, these hormones enhance collagen synthesis and prevent its breakdown by suppressing matrix metalloproteinases. Estrogen additionally promotes the production and deposition of glycosaminoglycans in the dermis, supporting wound healing.

Estrogen exhibits neuroprotective properties by inhibiting neuronal cell death in response to hypoxia or other insults. Its positive effects on angiogenesis may explain some of its beneficial actions on the central nervous system (CNS). On the other hand, progesterone acts on the hypothalamus to raise the set point for thermoregulation, leading to a slight increase in body temperature. This temperature change can be measured to determine whether ovulation has occurred. Progesterone also functions as a CNS depressant. The decline of progesterone levels during menstruation contributes to premenstrual dysphoria (premenstrual syndrome [PMS]). Additionally, progesterone affects the brainstem, increasing the sensitivity of the ventilatory response to PCO2, which results in increased ventilation and decreased PCO2 levels.

Estrogen plays a role in adipose tissue regulation by reducing its accumulation. It achieves this by decreasing lipoprotein lipase activity and increasing hormone-sensitive lipase, promoting lipolysis. Conversely, the loss of estrogen leads to adipose tissue accumulation, particularly in the abdominal region.

The transport and metabolism of ovarian steroids also play a crucial role in the overall physiological effects described above.
Estradiol-17β and progesterone fluctuate during the menstrual cycle, and they have multiple effects that can be categorized according to whether they are directly related to the reproductive system or not. Both hormones have profound effects on the ovary, oviduct, uterus, cervix, vagina, and external genitalia and on the hypothalamus and pituitary. Estrogen and progesterone also have important effects on nonreproductive tissues: Bone: Estrogen is required for closure of the epiphyseal plates of long bones in both sexes. Estradiol-17β has a bone anabolic and calciotropic effect (see ). It stimulates intestinal Ca++ absorption. Estradiol-17β is also one of the most potent regulators of osteoblast and osteoclast function. Estrogen promotes survival of osteoblasts and apoptosis of osteoclasts, thereby favoring bone formation over resorption. Low estrogen levels associated with menopause leads to bone loss and osteoporosis.
Liver: The overall effect of estradiol-17β on the liver is to improve circulating lipoprotein profiles. Estrogen increases expression of the LDL receptor, thereby increasing clearance of cholesterol-rich LDL particles by the liver. Estrogen also increases circulating levels of HDL. Estrogen regulates hepatic production of several transport proteins, including cortisol-binding protein, thyroid hormone–binding protein, and SHBG.
CHAPTER 44 The Male and Female Reproductive Systems
Cardiovascular organs: Premenopausal women have significantly less cardiovascular disease than men or post-menopausal women do. Estrogen promotes vasodilation through increased production of nitric oxide, which relaxes vascular smooth muscle and inhibits platelet activation. Single-nucleotide polymorphisms in the estrogen receptor have been associated with increased cardiovascular disease.
Integument: Estrogen and progesterone maintain healthy smooth skin with normal epidermal and dermal thickness. Estrogen stimulates proliferation and inhibits apoptosis of keratinocytes. In the dermis, estrogen and progesterone increase collagen synthesis and inhibit breakdown of collagen by suppressing matrix metalloproteinases. Estrogen also increases glycosaminoglycan production and deposition in the dermis and promotes wound healing.
CNS: Estrogen is neuroprotective—that is, it inhibits neuronal cell death in response to hypoxia or other insults. Estrogen’s positive effects on angiogenesis may account for some of the beneficial and stimulant-like actions of estrogen on the CNS. Progesterone acts on the hypothalamus to increase the set point for thermoregulation, thereby elevating body temperature approximately 0.5°F. This is the basis for using body temperature measurements to determine whether ovulation has occurred. Progesterone is a CNS depressant. Loss of progesterone on demise of the corpus luteum of menstruation is the basis for premenstrual dysphoria (premenstrual syndrome [PMS]). Progesterone also acts on the brainstem to sensitize the ventilatory response to PCO2 so that ventilation increases and PCO2 decreases.
Adipose tissue: Estrogen decreases adipose tissue by decreasing lipoprotein lipase activity and increasing hormone-sensitive lipase (i.e., it has a lipolytic effect). Loss of estrogen results in accumulation of adipose tissue, especially in the abdomen.
Transport and Metabolism of Ovarian Steroids