Understanding Menopause: Symptoms and Causes

1. PhytoestrogensDr Ghafghazi, Professor of Pharmacology Isfahan University of Medical Sciences and a member of R&D Department of Goldaru Co.

2. Menopause Menopause known as the ''change of life'' is the point in a woman's life when menstruation stops permanently , signifying the end of her ability to have children . Menopause is the last stage of a gradual biological process in which the ovaries reduce their production of female sex hormones--a process that begins about 3 to 5 years before the final menstrual period . This transitional phase is called the climacteric , or perimenopause .

3. Menopause is considered complete when a woman has been without periods for 1 year ., timing varies from person to person .

4. HOW DOES IT HAPPEN? The reproductive system is regulated by hormones . The ovaries contain structures called follicles that produce eggs for fertilization . A woman is born with about 2 million undeveloped eggs and by puberty there are about 300,000 left . Only about 400 to 500 ever mature fully to be released during the menstrual cycle . The rest will degenerate over the years .

5. For unknown reasons , during the mid – thirties , the ovaries begin to reduce hormone production . IN the late forties , the process accelerates and hormones fluctuate more , causing irregular menstrual cycles and unpredictable episodes of heavy bleeding . By the early to mid – fifties , periods finally end altogether . However , estrogen production does not completely stop .

6. At menopause , hormone levels don't always decline uniformly . They alternately rise and fall again . Changing ovarian hormone levels affect the other glands in the body , which together make up the endocrine system . The endocrine system controls growth , metabolism and reproduction . This system must constantly readjust itself to work effectively .

7. Ovarian hormones also affect all other tissues , including the breasts , vagina , bones , blood vessels , gastrointestinal tract , urinary tract , and skin .Menopause officially occurs after women stop menstruating . By the age of 55, 99% of women reach menopause .

8. PERIMENOPAUSE The years prior to menopause are known as perimenopause . This is a time when a woman is still menstruating but may experience some symptoms of menopause . During this time estrogen and progesterone levels begin to decline , so women experience missed cycles and symptoms of menopause/ perimenopause .

9. COMMON SYMPTOMS Both perimenopause and menopause are typically characterized by hormonal and physical changes often accompanied by emotional and psychological fluctuations . It is important to remember that perimenapuase and menopause are individualized processes that differ for each woman Symptoms can vary among different women . Some women can have symptoms that last as long as 5 years while some women will only have them for 1 year . Common symptoms include .

10. Menopausal symptoms are more common in women living in the west than in other parts of the world . Mental attitude towards the menopause is very important and it has been noted that in more traditional cultures , where older women are more respected and valued for their wisdom , the attitude to the menopause is more positive and far fewer symptoms are experienced.

11. A broad range of menopausal symptoms include: • »Irregular menstruation • »Vaginal itching or dryness • »Hot flushes / night sweats • »Palpitations • »Depression • »Headaches • »Irritability • »Sleeplessness • »Fatigue • »Weight gain • »Increased urination frequency • »Fluid retention • Some of these symptoms can be attributed to declining production of oestrogen

12. HOT FLASHES , NIGHT SWEATS , AND INSOMNIA These occur in 85% of women . Hot flashes usually last between three and six minutes and may occur several times a day. They can be disabling and physically draining . They can be associated with profuse sweating and can be quite embarrassing . They can also cause insomnia . Hot flashes generally begin suddenly on the chest , neck and face .

13. Hot flushes / night sweats ~ As many as 75% of menopausal women experience hot flushes ; they vary in intensity and frequency and may recur over months , or even years. This refers to the dilation , or relaxation , of the tiny blood vessels near the skin , leading to a rise in skin temperature and flushing of the skin. Increased heart rates , headaches , dizziness , weight gain , fatigue or insomnia may accompany hot flushes.

14. Vaginal dryness or 'burning' ~ Noticed particularly during sexual intercourse , the normal lubrication produced is considerably less in women who are not very sexually active . This can result in a burning sensation , which can become quite painful if the situation is not addressed . lubrication should be maintained with the aid of a proprietary brand of feminine lubricant .

15. EARLY MENOPAUSE Normally , menopause occurs between the ages of 40 -55. However, there are situations where the age may be a lot younger . A total hysterectomy (removal of the uterus and ovaries) may be advised for health reasons , if ovarian cysts or cancer have been detected . This sudden change in state results in an early menopause , often with little support or understanding for the woman concerned .

16. Treatment of Menopause • Estrogen Replacement Therapy (ERT) • thought to cause cancer • Replaced by Phytoestrogens • Taken in through diet. • Better form of estrogen therapy

17. What are Phytoestrogens? • -Naturally occurring chemicals derived from plants with a structure similar to estrogen • -The two main groups of phytoestrogens • -Isoflavones • -Lignans

18. Isoflavones

20. Why do plants make these? Self defense

21. Why do we care? We can absorb these compounds too!

22. The effect of phytoestrogens on humans -Cancer -Reproductive system -Osteoporosis, CVD, and Cholesterol

23. Cancer Asian/American studies -Asian populations have a lower level of hormone-dependent cancers -Post and Premenopausal women

24. How Phytoestrogens may reduce the risk of breast cancer 1.Suppress or inhibit normal estrogen production 2. Prevent the formation of new blood vessels by acting as antiangiogenesis factors 3. Act as antioxidants 4. Prevent tumor growth 5. Increase the excretion of estrogens in to the urine and feces

25. Cancer Cell cultures -Phytoestrogens reduce growth of cancer cell cultures -Different concentrations = Different effects in cells

26. Reproductive system Humans -Menstrual cycle changes -Hot flashes frequency

27. Osteoporosis -Phytoestrogens have been shown to stimulate osteoblasts activity -There is an optimal dose range of pure genistein -Studies show isoflavons increased bone mass

28. CVD and Cholesterol -Lower CVD in Asian populations may suggest phytoestrogens are cardioprotective -Inclinical trials, 4 7g of soy protein significatly decreases total cholesterol, LDL, and triglicerides -Men, 1L soy drink = 9.3% total cholesterol, 11.3% LDL -Postmenopausal women, 40mg isoflavones in a pill=22% lower cholesterol

29. The numbers -Americans consume less than 5 mg per day -Asian countries consume 25-100mg per day

30. Amount in foods

31. Amount in foods

32. HERBAL REMEDIES Herbs can provide powerful support during the pausal transition , because they contain phytoestrogens (plant Estrogens) , which have estrogen- like effects . Phytoestrogens have a normalizing effect . While phytoestrogens mimic estrogens , they are 1/400th as potent as synthetic estrogen . For menopausal symptoms , it was found that phytoestrogen – containing herbs may offer significant advantages over prescribed estrogen .

33. Phytoestrogens , taken in the recommended dose , are not associated with side effects , while estrogen replacement may pose significant health risks , including gallbladder disease , increased risk of cancer and stroke . However , in women with estrogen dependent breast cancer , soy isoflavones are not recommended .

34. SOY ISOFLAVONES Eating soy and soy isoflavones is the most popular way to increase estrogen . Current evidence suggests that Soy has estrogenic properties and can act like hormones to help maintain normal cholesterol levels and reduce the risk of thinning bones in post menopausal women . Soy is a powerful food , rich in estrogen – like , isoflavones . Isoflavones have been well studied for their beneficial health effects , including the relief of menopausal symptoms . Soy also contains iron , zinc , B vitamins , Vitamins , E and EFA .

35. A soy study enrolled 177 women in 16 centers . All of the women were complaining of at least five hot flashes a day . After 12 weeks on a soy extract containing 50 mg of genistin and 50mg of daidzin a day , the women reported less severe hot flashes and a dramatic 60% decline in night sweats . Other double blind research has reported significant reduction in the number of hot flashes .

36. Soyagol Tablet

37. CHASTEBERRY / VITEX Chasteberry , a whole fruit , provided as an extract , contains several different components , though to be medicinally active . Clinical studies over the past 40 years have shown that chastetree berries help balance estrogen and progesterone levels . They do this by influencing the pituitary glands and the hypothalamus , which in turn helps normalize FSH (follicle stimulating hormones) and LH (luteinizing hormones) production causing estrogen to be produced . In addition , chaste tree berries helps control symptoms associated with menopause including hot flashes , dizziness , vaginal dryness and depression .For this reason chastetree berries are one of the most commonly prescribed hebs in Europe for the treatment of perimenopausal symptoms .

38. Czech researchers recently conducted a double blind , placebo controlled clinical trial on vitex was well tolerated . Herbalist David Hoffmann reports that the most important use of Chaste Tree in England is for treating menopause symptoms , and that this is the only female health situation in which he uses chaste Tree by itself . For relieving symptoms

39. Agnogol Tablet

40. VITEX AGNUS – CASTUS Currently , Vitex is promoted for the symptomatic treatment of gynecological disorders including corpus luteum insufficiency and hyperprolactinemia , premenstrual syndrome (PMS) , menstrual irregularities , cyclic mastalgia. It was also used historically for treatment of endometrial hyperplasia and secondary amenorrhea ; endocrine dependant dermatoses (dermatitis dysmenorrheal symmetrica , acne vulgaris , eczema , acne rosacea), hypermenorrhea , infertility due to hyperprolactinemia and luteal phase defect ; Insufficient lactation .

41. More recent clinical data have indicated that vitex preparations may be used to treat fibroid cysts and infertility , to stop miscarriages due to progesterone insufficiency , to flush out the placenta after birth and also as a digestive aid , sedative , anti – infective and for the treatment of hot flashes .

42. Constituents Vitex agnus castus contains: Flavonoids iridoids and diterpenes Flavonoids include castican, orientin , and isovitexin Iridoids include agnuside and aucubin

43. EXPERIMENTAL EVIDENCE A variety of extracts of the fruit act as dopamineagonists in vitro and in vivo . The binding of an ethanol extract of the fruit and various extract fractions of the extract to the dopamine D2 and other receptors were valuated both by radioligand binding studies and by superfusion experiments . The D2 receptor antagonist spiperone antagonized the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation .

44. Several groups have demonstrated that extracts of chaste berry bind to the estrogen receptor and have weak estrogenic effects , suggesting that chaste berry may also affect the estrogen/progesterone balance . Incubation of recombinant human estrogen receptors expressed in yeast cells with 50-200 µg/ml of a fruit extract , resulted in the binding o the extract to ER and a dose-dependent increase in the production of galactosidase , indicating a weak estrogenic effect .

45. CLINICAL STUDIES Over 32 clinical trials have assessed the safety and efficacy of various fruit extracts or tinctures (53-70% ethanol) for the treatment of , corpus luteum insufficiency , cyclic breast pain , hyperprolactinemia , menopausal symptoms , premenstrual syndrome , uterine bleeding disorders , and miُُcellaneous menstrual irregularities .

46. During the past 50 years at least 17 clinical studies have assessed the effects of extracts of the fruit on a variety of menstrual cycle disorders including amenorrhea , oligomenorrhea , polymenorrhea , corpus luteum insufficiency and infertility . Two double – blind placebo – controlled clinical trials and several observational studies have investigated the effect of various fruit extracts on corpus luteal phase disfunction and infertility .

47. A randomized , double – blind , placebo – controlled trial assessed the efficacy of a dried fruit extract on infertility (Milewicz et al 1993) . The aim of the study was to determine of elevated pituitary prolactin could be reduced and of deficits in luteal phase length and luteal phase progesterone synthesis was normalized .Blood for hormone analysis was taken at days 5-8 and day 20 of the menstrual cycle , before and after three months of therapy .

48. Latent hyperprolactinaemia was analyzed by monitoring the prolactin release 15 and 30 min after intravenous administration of 200 mg of thyroid hormone . Thirty – seven cases (placebo : n = 20 , treatment : n = 17) were included in the statistical analysis . After 3 months of treatment , prolactin release was reduced , a significant increase in the length of the luteal phase (10.5 days ; p< 0.05) was observed and deficits in luteal progesterone synthesis were eliminated .

49. A randomized , double- blind , placebo – controlled clinical trial involving 104 women with cyclic breast pain (at least 3 cycles ) the effects of a preparation of the fruit ( 10 g tincture containing 2 g of crude drug in 53% ethanol – VAC )for the treatment of cyclic breast pain . The patients were treated with placebo .VAC solution ( 30 drops twice daily ) . or VAC tablet ( one tablet twice daily ) for 3 cycles .

50. Patients assessed the intensity of breast pain once per cycle using a Visual Analog Scale and also recorded the presence of menstrual bleeding and the intensity of pain in a diary . Prolactin levels were also measured during the premenstrual week of cycles 1 and 3 . At the end of the third cycle of treatment , a significant reduction in breast pain was observed in the treated patients as compared with placebo ( VAC solution ,P= 0.006 ; VAC tablets , P = 0.007).