Chadwick LR, Pauli GF, Farnsworth NR. The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties Phytomed. 2006;13:119-131.An increasing number of women are experiencing symptoms associated with the biochemical changes of menopause. The difficulties associated with this phase in a woman's life include hot flashes, anxiety, insomnia, and osteoporosis. According to the authors, hormone replacement therapy (HRT) with equine estrogens is very effective 'in reducing vasomotor symptoms, such as hot flashes, and in curtailing osteoporosis.' While there have always been significant side effects associated with the use of synthetic estrogen, equine estrogens have drastically decreased in favor among women since the publicity surrounding the Women's Health Initiative (WHI). This multi-center study was cut short when researchers discovered that women receiving a combination of equine estrogen plus progestin had a significantly increased risk of developing breast cancer.1 Within eight months of the termination of this study, 56% of women discontinued their use of HRT.
There is, therefore, a great need for safe and effective therapeutic agents to assist women with hormonal balance and disease prevention during the menopausal years. Phytoestrogens estrogenic substances of botanical origin that bind to human estrogen receptors have traditionally been used for this purpose. More than 20 classes of phytochemicals are natural estrogen receptor (ER) ligands; the five most potent are the steroids, the polyketides (zearalenones), the alkylated flavanones, the isoflavones and the phenylbenzofurans. Formulations from soy (Glycine max) and red clover (Trifolium pratense) suggest clinical efficacy in both in vitro and in vivo research. However, there is very little clinical data available for phytoestrogens other than the isoflavonoids.
Several types of assays have been designed to identify and/or characterize estrogenic activity, such as in vitro ligand-receptor binding and whole cell assays, as well as in vivo animal models. With the discovery of the beta-estrogen receptor (ERbeta) subtype, scientists have begun to investigate the organ-specific effects of each receptor subtype.
The present paper reviews the biochemical and folkloric literature, as well as the only two human clinical trials on the effect of hops on menopausal symptoms. 'Hops' refers to the strobiles, or 'cones' of female individuals of the species Humulus lupulus. [Note: Strobile is defined as a cone-like inflorescence (a cluster of flowers).] In contrast to other botanicals, the agricultural methods for the cultivation, harvesting and processing of hops have been carefully optimized in order to safeguard its prized organoleptic properties for the production of beer. The hops strobiles are harvested in late August or September in the northern hemisphere. The cones are dried by forced hot air and are often pressed into cylindrical pellets that reduce chemical oxidation/degradation by reducing surface area.
Of the more than 1000 chemicals that have been identified in hops, the bitter acids and volatile oils of the inflorescences have the most economic value because of their use in beer manufacturing. Hops also contains a 1:1 racemate of (plus/minus)-8-prenylnaringenin, also termed 8-isopentenylnaringenin (8PN), a prenylated flavonoid, and 'one of the most potent in vitro estrogenic substances known from the plant kingdom.' The authors point out that the name 8-prenylnaringenin is misleading from a phytochemical standpoint, and they suggest that the term 'hopein' used in the English hops literature be used instead 'when referring to the estrogen from hops.'
The medical literature on the estrogenic properties of hops dates back to 1953 when Koch and Heim published a one-page report stating that hops contains 'the equivalent of 20-300 mcg estradiol/g.'2 Their work was motivated by the folk legend that women who came from distant places to work in the hops gardens would begin to menstruate two days after starting to pick hops. In 1960s and 1970s, several papers were published, and several patents exist, for the external use of hops in cosmetics. In the 1970s, 1980s and 1990's, journal articles from the U.S., Iran, Romania, and France referred to the traditional use of hops in the treatment of gynecological disorders. For example, in Germany brewery sludge baths containing 30% hops extracts were used for gynecological problems. However, it is the 1999 report by Milligan et al. that 'may be regarded as the beginning of the modern, unambiguous understanding of the in vitro estrogenic activity of hops.' 3
Milligan and his team isolated and characterized '8PN as the major estrogenic substance in hops and one of the most potent known plant estrogens.' Subsequent research has demonstrated that 8PN mimics the action of 17beta-estradiol. 8PN has 10-20,000-fold less potency than estradiol for ERbeta. However, it has a much greater affinity for the ERalpha receptor, where it is only 70-fold less potent than estradiol. When racemic 8PN is separated and assayed, there is 'no significant difference in ER binding potency between the 2R and 2S forms.' The authors refer to a study that has potential import in the debate about the use of phytoestrogens in breast cancer patients. According to the authors, Kitaoka et al. (1998) reported that 8PN 'stimulates the growth of estrogen-dependent MCF7 breast cancer cells. 4 [Note: Upon reading the abstract, it appears that this may not be the correct citation for this information. For another paper on this topic see: Matsumara A, Ghosh A, Page GS, Darbre PD. Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol. 2005; 94(5):431-443.] 5
Most of the research on 'well-defined hop preparations' that has been published to date focuses on the sedative properties of hops. Of the 73 drugs listed under 'Hypnotic/sedative plant drugs' in The German Red Book, 43 contain hops. Most of these preparations also contain other plant extracts. The authors were able to identify only one clinical trial that focused specifically on the estrogenic properties of hops.6 The formula used in this study contained a combination of hops and an unspecified Crataegus spp. that was effective in treating hot flashes. However, the preparation 'was neither chemically nor biologically standardized by any modern standards.' The second clinical trial on menopausal symptoms evaluated two different polyherbal blends one given in the morning, and the other (containing hops) given in the evening.7 Although the formulas were effective in alleviating menopausal symptoms, this research did not reveal specific information about the estrogenic properties of hops.
The authors conclude: 'Preparations of hops that contain 8PN must be considered 'estrogenic.'' Considering the traditional use of hops for both estrogenic and sedative properties, it is 'a reasonable hypothesis that properly formulated hop preparations can have a rational place in modern medicine.' However, while there is some clinical evidence to support the therapeutic efficacy of hops as a sedative 'it is still open to debatewhether or not they can have beneficial hormonal activity when consumed orally by humans.' Randomized, double blind, placebo-controlled clinical trials are necessary to document this hormonal activity, as well as to establish dosage forms and officially recognized standards for estrogenic formulations of hops.
Cathleen Rapp, N.D.
1Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002; 288:321-333.
2 Koch W, Heim G. Östrogene harmone in Hopfen and Bier. Muench Med Wochenschr. 1953; 95:845.
3 Milligan SR, Kalita JC, Pocock V, Van De Kauter V, Stevens JF, Deinzer ML et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J. Clin. Endocrinol. Metab. 85:4912-4915.
4 Kitaoka M, Kadokawa H, Sugano M, Ichikawa K, Taki M, Takaishi S et al. Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship. Planta Med. 1998; 64:511-515.
5 Matsumara A, Ghosh A, Page GS Darbre PD. Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells. J Steroid Biochem Mol Biol. 2005;94(5):431-443.]
6 Goetz P. Traitment des bouffees de chaleur par insuffisance ovarienne par l'extrait de houblon (Humulus lupulus). Rev Phytother Prat. 1990; 4:13-15.
7 Sun J. Morning/evening menopausal formula relieves menopausal symptoms: a pilot study. J Altern Complement Med. 2003; 9:403-409.