**3. Melatonin involvement into hormonal regulation of female reproductive system functions and its aging**

In 1963 R.J. Wurtman et al. reported for the first time that exogenic intake of melatonin causes weight reduction in female rat ovaries. Since those times many evidences that pineal gland and its main hormone, melatonin, influence reproductive function have been received. Studies showed that neurons in preoptic and mediobasal areas of hypothalamus and hypophysis represented the main points, through which melatonin produced its reproductive action. The main physiological effect of melatonin lies in the slowdown of gonadotrophin secretion, with greater suppression of the lutenizing hormone (LH) by melatonin rather than the follicle-stimulating one. Negative correlation is registered between melatonin level at night and lutenizing hormone concentration. In addition, secretion of other tropic hormones of hypophysis anterior lobe (such as corticotrophin, thyrotropin, somatotropin) is reduced, though to a lesser extent. Melatonin can be called a universal inhibitor of endocrine function in a female body [10].

Melatonin takes part in regulation of many vital physiological processes, such as puberty and genital formation, menstrual cycle, and aging of reproductive system. High level of nocturnal melatonin was found in children with delayed puberty, while among children having accelerated puberty, a decrease in melatonin secretion at night was noted. High levels of melatonin among children produce a dominating effect on pulsatile gonadotropin secretion, ovary function, and puberty [4].

Abnormal levels of melatonin in blood are connected with a number of malfunctions in the system "hypothalamus—hypophysis—ovaries." This gives boost to precocious puberty or its delay and formation of hypothalamic or hypergonadotropic amenorrhea. Therefore, melatonin may have indirect influence on the function of reproductive glands through its intervention into the secretion of gonadotropinreleasing hormone and/or secretion of gonadotrophins. Some data demonstrate that melatonin can also be synthesized in reproductive glands. Decreased melatonin secretion in summer coincides with higher fertility among women living in the Northern Hemisphere [11].

Based on these data, it was presupposed that melatonin could be a part of events preceding activation of hypothalamus-ovary axis during a puberty period [12]. Non-serial MRI of female head region helped register a reliable decrease in pineal gland volume during the ovulatory phase as well as while perimenopause. It indicates pineal gland involvement into "turning off " female reproductive function [13].

Melatonin may also produce direct influence on ovaries. High level of melatonin was found in preovulatory follicular fluid with triple concentration as compared to blood. Connecting areas of iodine melatonin were identified in human cells of granulosis and preovulatory follicles.

**39**

*Role of Pineal Hormone Melatonin in a Woman's Life: From Conception to Decline of Life*

Antioxidative effect of melatonin is considered to be the most prominent one. It has been determined that melatonin ties free radicals of oxygen and at the same time stimulates enzymatic systems and SOD and possesses protective properties in

It's generally known that macrofags, neutrophils, and vascular endothelium cells located in follicles produce AOS during ovulation. Despite the fact that AOS (active oxygen species) participate in breaking follicles, potentially they may damage an ovum and granulosis lutein cells. AOS inhibit progesterone production by lutein cells due to inhibition of steroidogenesis enzymes and transport intracellular protein. Melatonin is an important antioxidant in ovary follicles and enables progesterone synthesis by luteal cells [15]. Research outcomes have shown that melatonin intake leads to increased concentration of this hormone in follicular fluid and reduced oxidative damage inside follicles, thus raising a chance of fertilization and pregnancy [16, 17]. Melatonin intake also improved progesterone synthesis among women with infertility issues caused by insufficiency of the cycle luteal phase [18]. Pregnancy and acts of delivery are characterized by deep alterations in the endocrine profile of a female body as well as in pineal gland operation. In the case of physiological pregnancy, increased melatonin excretion with urine is marked, while

Decreased melatonin level is noted in the case of threatening miscarriage [4]. At the same time, many scientists speak about the great importance of melatonin in the body aging process. It is also pointed out that from the age of 45, melatonin starts to decline steadily till the end of human life. Numerous studies have demonstrated the correlation between melatonin synthesis and menopause onset [19]. The second decrease in melatonin level may be related to involutory

In a placebo-controlled clinical study, it was established that there was a connection between decreased content of nocturnal melatonin in saliva and menopause onset, while intake of 3 mg of melatonin by female patients during perimenopause on a daily basis for 6 months eliminates hormonal and neurovegetative disorders

Women in postmenopause had lower concentration of melatonin in blood serum

as compared to women in perimenopause, with a shorter duration of melatonin secretion in postmenopause as a rule, while melatonin synthesis peak time (acrophase) was almost the same. A pattern was determined that as melatonin secretion peak occurs later among women in perimenopause, anxiety level gets higher (*p* = 0.022), and as melatonin secretion continues for a longer period, the quality of

Some scientists suggest using melatonin drugs at the first stage of climacteric disorder treatment even before the start of hormonal therapy of menopause [4]. Moreover, in a double-blind placebo-controlled clinical study, it was determined that prescription of menopause hormonal therapy to postmenopausal women shifts melatonin secretion peak time without changing the melatonin level in the blood serum, which requires further research [21]. Other authors did not found in their research analyses devoted to alternative therapy for climacteric disorders any

A growing number of evidences are emerging, which point to melatonin involvement into lipid metabolism. The study of H. Tamura was devoted to melatonin influence on lipid metabolism among women in perimenopause and

*DOI: http://dx.doi.org/10.5772/intechopen.88999*

relation to free-radical damage of DNA [14].

just before an act of delivery its level plummets.

and recovers menstruation cycle and thyroid function [20].

convincing data on hot flash arresting by melatonin drug [22].

life among patients gets better (*p* < 0.001) [21].

**4. Melatonin lipid metabolism**

processes in pineal gland [13].

*Role of Pineal Hormone Melatonin in a Woman's Life: From Conception to Decline of Life DOI: http://dx.doi.org/10.5772/intechopen.88999*

Antioxidative effect of melatonin is considered to be the most prominent one. It has been determined that melatonin ties free radicals of oxygen and at the same time stimulates enzymatic systems and SOD and possesses protective properties in relation to free-radical damage of DNA [14].

It's generally known that macrofags, neutrophils, and vascular endothelium cells located in follicles produce AOS during ovulation. Despite the fact that AOS (active oxygen species) participate in breaking follicles, potentially they may damage an ovum and granulosis lutein cells. AOS inhibit progesterone production by lutein cells due to inhibition of steroidogenesis enzymes and transport intracellular protein. Melatonin is an important antioxidant in ovary follicles and enables progesterone synthesis by luteal cells [15]. Research outcomes have shown that melatonin intake leads to increased concentration of this hormone in follicular fluid and reduced oxidative damage inside follicles, thus raising a chance of fertilization and pregnancy [16, 17]. Melatonin intake also improved progesterone synthesis among women with infertility issues caused by insufficiency of the cycle luteal phase [18].

Pregnancy and acts of delivery are characterized by deep alterations in the endocrine profile of a female body as well as in pineal gland operation. In the case of physiological pregnancy, increased melatonin excretion with urine is marked, while just before an act of delivery its level plummets.

Decreased melatonin level is noted in the case of threatening miscarriage [4].

At the same time, many scientists speak about the great importance of melatonin in the body aging process. It is also pointed out that from the age of 45, melatonin starts to decline steadily till the end of human life. Numerous studies have demonstrated the correlation between melatonin synthesis and menopause onset [19]. The second decrease in melatonin level may be related to involutory processes in pineal gland [13].

In a placebo-controlled clinical study, it was established that there was a connection between decreased content of nocturnal melatonin in saliva and menopause onset, while intake of 3 mg of melatonin by female patients during perimenopause on a daily basis for 6 months eliminates hormonal and neurovegetative disorders and recovers menstruation cycle and thyroid function [20].

Women in postmenopause had lower concentration of melatonin in blood serum as compared to women in perimenopause, with a shorter duration of melatonin secretion in postmenopause as a rule, while melatonin synthesis peak time (acrophase) was almost the same. A pattern was determined that as melatonin secretion peak occurs later among women in perimenopause, anxiety level gets higher (*p* = 0.022), and as melatonin secretion continues for a longer period, the quality of life among patients gets better (*p* < 0.001) [21].

Some scientists suggest using melatonin drugs at the first stage of climacteric disorder treatment even before the start of hormonal therapy of menopause [4]. Moreover, in a double-blind placebo-controlled clinical study, it was determined that prescription of menopause hormonal therapy to postmenopausal women shifts melatonin secretion peak time without changing the melatonin level in the blood serum, which requires further research [21]. Other authors did not found in their research analyses devoted to alternative therapy for climacteric disorders any convincing data on hot flash arresting by melatonin drug [22].
