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SCIENTIFIC INFORMATION
Reproduced from www.pharmaceutical-int.com/article.asp?pubID=13&catID=631&artID=1058
INNOVATIVE APPLICATIONS OF HOPS (Humulus lupulus L.)
FOR RELIEF OF MENOPAUSE RELATED SYMPTOMS
Professor Denis.De Keukeleire University of Gent, Belgium
Menopause is best described as the period in which a woman, as a result of
a decreased oestrogen and progesterone production by the ovaries, turns
from fertile into infertile condition. Women are confronted with this on
average when they are around 50 years old.
The so-called ‘transition’ – which is not a disease,
and to balance the increased risk of breast cancer, but a natural phenomenon – lasts a few years. which appears after only 2 years of therapy, against Menopause can be divided in two stages: the peri- the decreased risk of uterus cancer. The present menopause and the post-menopause. During the strategy of doctors may also be influenced by an peri-menopause, women feel the first menopausal American study, which has just been published in symptoms, one of these are hot flushes, caused by the medical journal valued most highly in the world, unusual fluctuations in the hormone levels and New England Journal of Medicine (5). A significant accompanied by very irregular menstruation cycles. rise in the cardiovascular disease risk was found The post-menopause starts as soon as 12 months during the 1st year of combination HRT. In the past, have gone by since the last menstruation. For many it was believed that HRT would protect women from women, the transitional process involves a range of symptoms and discomforts: hot flushes and wavesof heat, sleeping disturbances, structural changes in bladder and vagina, strongly reduced libido, higher impression, both on doctors and on patients, not cardiovascular disease risks, decrease of bone only in the United States, but worldwide (in our density (osteoporosis or bone decalcification) with country as well). The market for HRT products in an increased risk of hip, leg and arm fractures. the United States and in England has collapsed andit may be stated that HRT at this moment can only Hormone replacement therapy under debate
be supported in very serious cases of menopausalcomplaints and osteoporosis among women with a Medicalisation of menopause is a ‘hot’ item. Women limited cancer risk. There is no more room for long can expect to live for about 30 years after term HRT, especially not when the treatment is menopause. For a healthy, active and fulfilling post- menopausal life, women need to make some efforts,whether by adapting their lifestyles, of which Control of menopausal symptoms through
nutrition is a part, or by taking extra nutritional oestrogenic plants
supplements and/or treatment with medication. An adequate means for fighting the symptoms involved In these severe health problems, nature can be of in menopause is the well-known hormone
great help. The fact is that many plants contain so- replacement therapy (HRT), in which women, in
called phyto-oestrogens (‘phyto’ means ‘plant
general orally, take a small dose of semi-synthetic derived’); these are non-steroidal constituents, hormones. On July 9, 2002 however, the American which bear a structural resemblance to endogenous Women’s Health Initiative (WHI), a large-scale, oestrogens and which imitate their activity. Phyto- long-term study (8,5 years) on the advantages and oestrogens are able to fill up the hormone deficiency disadvantages of HRT, in which 16,608 menopausal in menopausal women in a natural way and to women (50-79 years old) were involved, was relieve menopausal symptoms (6). An important broken off after 5.2 years (1), as the risks of additional advantage is that, since the hormonal invasive breast cancer, arterial rupture, stroke and activity of phyto-oestrogens is much weaker than lung embolism were raised significantly. The that of the hormones of the body itself, the advantages in relation to a reduced risk of hip influence on hormone dependent cancers, such as fractures and cancers of the large intestine and of breast and uterus cancers, is weakened.
the uterus were outweighed by this (2). Moreover, on December 11, 2002, the federal US government Plants, which are rich in oestrogens, normally do published its two-yearly Report on Carcinogens, in not occur as such in western nutrition these days.
which the steroidal oestrogens, used in HRT and in As a result, they can only be ingested as derived oral contraceptives, were added as a group to the products or nutritional supplements. It is apparent official list of ‘known human carcinogens’ (3). In the that menopausal women are massively switching report, the increased cancer risks, especially breast from HRT to alternative preparations, based on natural phyto-oestrogens with a suitable safety profile. Numerous clinical studies support the Very recently, the results of the British Million activity of phyto-oestrogens in relation to Women Study, in which 1 million menopausal menopausal symptoms, while there are also strong women were involved, were published in the leading epidemiological indications of a causal connection magazine Lancet (4). The conclusion of this largest between a typically Asian diet, in which oestrogen study ever on the relation between HRT and breast rich soy plays an important role, and the limited cancer, was that HRT (combination of oestrogens incidence of hormone-dependent cancers and and progestins) doubled the risk of breast cancer, menopausal complaints among Asian women.
versus a 30% rise for HRT with only oestrogens. In the last 10 years, 20,000 extra cases of breast Only a limited number of oestrogenic plants exist cancer were diagnosed among British women and they are used regularly in the treatment of between 50 and 64 years of age as a result of long- menopausal symptoms. In Belgium, it seems that term application of HRT. Doctors are advised to some 20 phyto-oestrogenic plants are commercially discuss HRT with their patients on a yearly basis available, derived from soy (Glycine max L., isoflavones, such as genistein and daidzein), red AUTHOR BIOGRAPHY
clover (Trifolium pratense L., coumestrol as active phyto-oestrogen), black cohosh (Cimicifuga Prof. Dr. Denis De
racemosa L.), chaste tree or chaste berry (Vitex Keukeleire,
agnus-castus L.) and yam (Dioscorea villosa L.) Hops (Humulus lupulus L.)
In 1999, the research team of Prof. Dr. Denis De Original applications of hops
Keukeleire of the Faculty of Pharmaceutical Sciences in the fight against
at the University of Ghent, published for the first menopausal symptoms
time that hops contain the strongest natural phyto- oestrogen, that is 8-prenylnaringenine, also called hopein, which belongs to the class of polyphenols, prenylflavonoids (7). This revealing and intriguing finding has meanwhile been confirmed by 5 independent research teams in Germany, England and Japan (8). What is more, a Japanese research team has discovered that hopein has a potent effect on bone decalcification (9), while a French research centre has shown that hops strongly reduce hot flushes (10). Hopein seems to be a ‘miracle molecule’ for menopausal women. Moreover, hops contain another substance, xanthohumol, which,
just like hopein, belongs to the prenylflavonoid group, but, in contrast to hopein, does not show any oestrogenic activity. At the German Centre for Cancer Research in Heidelberg, the anti-cancer property of xanthohumol was studied in detail as part of an extensive study, in which more than 2,000 vegetable compounds were examined by some 20 anti-cancer tests. Only xanthohumol was active in all tests, which illustrates the exceptional value of this compound of hops. Xanthohumol shows a remarkably broad spectrum of inhibition mechanisms at the initiation, promotion and The food supplements derived from hops available on the market at this moment are focused on the tranquilizing (sedative) effect of the plant.
Generally, these are combinations with other plants, such as valerian and lemon balm. Some 1% of the world production of hops (99% is intended for breweries) is used as such or as a simple watery- References
1. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal
women. Journal of the American Medical Association 288:321-333 (2002). S. Ramsay. Trial of HRT to prevent CHD halted early because of
increased harm. Lancet 360:146-146 (2002).
2. The American College of Obstetricians and Gynecologists (ACOG; www.acog.org), zie:
http://www.acog.org/from_home/publications/press_releases/nr08-30-02.cfm.
3. The Report on Carcinogens, 10th Edition, zie: http://ntp-server.niehs.nih.gov.
4. The American College of Obstetricians and Gynaecologists. Use of botanicals for management of menopausal symptoms, zie: http://www.acog.org/from_home/publications/misc/pb028.htm.
5. V. Beral and the Million Women Study collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 362:419-427 (2003)
6. H. N. Hodis et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. New England Journal
of Medicine 349:535-545 (2003).
7. S. R. Milligan, J. C. Kalita, A. Heyerick, H. Rong, L. De Cooman, D. De Keukeleire. Identification of a potent phytoestrogen in hops
(Humulus lupulus L.) and beer. Journal of Clinical Endocrinology and Metabolism 84:2249-2252 (1999). Vervolgpublicaties: R. S. Milligan, J.
C. Kalita, V. Pocock, V. Van de Kauter, J. F. Stevens, M. L. Deinzer, H. Rong, D. De Keukeleire. The endocrine activities of 8-prenylnaringenin
and related hop (Humulus lupulus L.) flavonoids. Journal of Clinical Endocrinology and Metabolism 85:4912-4915 (2000). S. R. Milligan, J. C.
Kalita, V. Pocock, A. Heyerick, L. De Cooman, H. Rong, D. De Keukeleire. Oestrogenic activity of the hop phyto-oestrogen, 8-
prenylnaringenin. Reproduction 123: 235-242 (2002).
8. N. G. Coldham, M. J. Sauer. Food and Chemical Toxicology 39:1211-1224 (2001). S. Gester et al. Tetrahedron 57:1015-1018 (2001). O.
Zierau et al. Planta Medica 68:449-451 (2002). O. Schaefer et al. Journal of Steroid Biochemistry and Molecular Biology 84:359-360 (2003).
T. Takamura-Enya et al. Food and Chemical Toxicology 41:543-550 (2003).
9. M. Miyamoto, Y. Matsushita, A. Kikokawa, C. Fukuda, Y. Iijima, M. Sugano, T. Akiyama. Estrogenic effects of 8-isopentenylnaringenin on
bone metabolism, Planta Medica 64: 769-769 (1998).
10. P. Goetz, Traitement des bouffées de chaleur par insuffisance ovarienne par l’extrait de houblon (Humulus lupulus) Revue de
Phytothérapie Pratique
(4):13-15 (1990)
11. C. Gerhauser, A. Alt, E. Heiss, A. Gamal-Eldeen, K. Klimo, J. Knauft, I. Neumann, H. R. Scherf, N. Frank, H. Bartsch, H. Becker. Cancer
chemopreventive activity of xanthohumol, a natural product derived from hop. Molecular Cancer Therapeutics 1: 959-969 (2002).

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