Hops: 8-Prenylnaringenin and Menopause

Table of Contents

1. What 8-Prenylnaringenin Is
2. "The Most Potent Phytoestrogen Known"
3. Where 8-PN Comes From
4. How Much Actually Reaches the Blood
5. What Animal and Cell Studies Show
6. What Human Trials Found
7. Where the Reviews Disagree
8. Bone, Tumour Growth and Other Hormone-Linked Research
9. Safety Questions
10. Does Beer Deliver 8-PN?
11. What Remains Unknown
12. Key Research Papers
13. Connections

What 8-Prenylnaringenin Is

8-PN is a prenylated flavonoid. "Flavonoid" places it in the large family of plant pigments and defence chemicals found in fruit, tea and vegetables. "Prenylated" means a small fatty side chain (a prenyl group) is attached, which changes how the molecule binds to proteins. Hops are unusual in producing a whole set of prenylated flavonoids: xanthohumol, isoxanthohumol, 6-prenylnaringenin and 8-PN (Stevens and Page, 2004).

A 2003 review of phytoestrogens divides them into four chemical groups — isoflavonoids (as in soy and red clover), flavonoids, stilbenes (such as resveratrol) and lignans (as in flaxseed) — and singles out the prenylated flavonoids, especially 8-PN, for their hormonal effects. Because phytoestrogens resemble oestradiol in shape, the review notes they may behave as selective oestrogen receptor modulators: switching oestrogen signalling on in some tissues and less so, or not at all, in others (Cos and colleagues, 2003).

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"The Most Potent Phytoestrogen Known"

This description appears in reviews of hop chemistry (Stevens and Page, 2004) and of beer compounds (Chen and colleagues, 2014), and a 2018 review is titled for 8-PN as "a potent phytoestrogen from hops" (Štulíková and colleagues, 2018). The ranking comes from laboratory assays — receptor-binding tests and cell experiments that compare how strongly different plant compounds activate oestrogen signalling.

Three caveats belong next to that phrase every time it is used:

1. The ranking compares plant compounds with each other. "Most potent phytoestrogen" does not mean 8-PN matches the body's own oestradiol, or hormone-therapy drugs.
2. Potency in a dish is not exposure in a person. How much 8-PN reaches the blood depends on the product and on metabolism (see below).
3. Potency cuts both ways. A compound strong enough to relieve oestrogen-deficiency symptoms is, by the same token, a compound whose long-term hormonal effects need checking.

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Where 8-PN Comes From

The hop plant makes xanthohumol, its principal prenylflavonoid, in its lupulin glands. Reviews note that human exposure to xanthohumol, 8-PN and isoxanthohumol comes primarily through beer (Stevens and Page, 2004), and that the hop prenylflavonoid pathway is a possible target for breeding or biotechnology aimed at raising 8-PN for pharmaceutical production.

In the body the compounds interconvert. Xanthohumol is metabolised to isoxanthohumol and, in smaller amounts, to 8-PN and 6-PN; both xanthohumol and 8-PN are further transformed into many flavonoid derivatives (Stevens and Page, 2004; Legette and colleagues, 2014).

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How Much Actually Reaches the Blood

The best human measurement in this citation set comes from a pharmacokinetic study of xanthohumol, the precursor (Legette and colleagues, 2014). Forty-eight adults (24 men, 24 women) took a single oral dose of 20, 60 or 180 mg of xanthohumol, and blood was sampled for five days.

• Xanthohumol and isoxanthohumol, mainly in their bound (conjugated) forms, were the dominant circulating compounds.
• 8-PN and 6-PN were undetectable in most participants.

So taking xanthohumol does not reliably deliver 8-PN, and a product's 8-PN content, not its xanthohumol content, matters for the hormonal question.

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What Animal and Cell Studies Show

A short 2016 review of hops for menopausal hot flushes summarised the laboratory picture (Abdi and colleagues, 2016):

• In animal studies, 8-PN reduced the pituitary hormones LH and FSH, increased serum prolactin and uterine weight, and induced overgrowth of the vaginal lining — each a recognised sign of oestrogen action in the body.
• In cell studies, hop extract bound strongly to both oestrogen receptors (alpha and beta) and switched on oestrogen-responsive genes in Ishikawa cells, a human uterine-lining (endometrial) cancer cell line widely used to test oestrogen activity.

Those are the effects you would expect from a genuine oestrogen. They support the idea that 8-PN could ease symptoms caused by falling oestrogen. The effects on the uterus and vaginal lining are also the reason the safety questions below matter.

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What Human Trials Found

The citation set for this page contains reviews of the human trials rather than the trial reports themselves, so the results are described as the reviews summarise them:

• Conflicting results. A 2014 mini-review in Maturitas of herbal preparations for menopause beyond isoflavones and black cohosh stated that randomised controlled trials of the hop flavonoid 8-PN gave conflicting results (Depypere and Comhaire, 2014).
• "Promising". A 2018 review of 8-PN stated that its use in menopause had been clinically examined with promising results, while stressing that precise evidence and further safety work are needed (Štulíková and colleagues, 2018).
• Reductions in hot-flush frequency. The 2016 review reported that numerous clinical trials documented significant reductions in hot-flush frequency with hop-containing preparations, and that larger, longer trials are needed to confirm this (Abdi and colleagues, 2016).

Read together: small trials, some positive, some not, with no large long-term trial to settle it.

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Where the Reviews Disagree

The most recent broad review in this set reaches a cooler verdict. Assessing herbal products for menopause and gynaecological complaints, Kenda and colleagues (2021) concluded that black cohosh and red clover were consistently shown to reduce menopausal symptoms in clinical studies, while the available data do not fully support fenugreek, hops, valerian and soy for this purpose.

A 2016 pharmacology review of botanicals for women's health lists hops among plants with oestrogenic activity used for menopausal symptoms, alongside soy, red clover, kudzu, licorice, rhubarb, chasteberry, flaxseed, horny goat weed and alfalfa, and notes that some oestrogenic botanicals have shown protective effects against bone loss (Dietz and colleagues, 2016). It does not rank hops as proven.

The disagreement is mostly about how much weight to put on small trials, not about the laboratory facts, which no review disputes.

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Bone, Tumour Growth and Other Hormone-Linked Research

Beyond hot flushes, the 2018 review lists 8-PN research on preventing bone resorption (the breakdown of bone that accelerates after menopause) and on inhibition of tumour growth (Štulíková and colleagues, 2018). Reviews of phytoestrogens in general also discuss possible protective properties against hormone-dependent breast and prostate cancers and cardiovascular disease (Cos and colleagues, 2003). In this citation set these are review-level descriptions of mainly laboratory and animal work; no human trial of 8-PN for bone or cancer outcomes appears.

For context on hormone therapy itself, Dietz and colleagues (2016) note that interest in botanicals for menopause rose after the Women's Health Initiative found an increased breast-cancer risk with conventional hormone therapy. A plant oestrogen strong enough to act like a hormone raises the mirror-image question of whether it shares any of hormone therapy's risks; that question has not been answered by long-term trials.

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Safety Questions

• Long-term use. The 2018 review states that the use of phytoestrogens is frequently questioned regarding possible adverse effects of long-term consumption and calls for investigations to define the safety risks of therapeutic 8-PN use (Štulíková and colleagues, 2018).
• Untested for toxicity and interactions. Botanicals for women's health, though perceived as natural and safe, have not been rigorously tested for potential toxic effects or drug–botanical interactions (Dietz and colleagues, 2016).
• Breastfeeding. LactMed reports that some sources advise against hops during breastfeeding because of its phytoestrogen content, and that no data exist on hop components in breast milk or on safety in nursing infants.
• Hormone-sensitive conditions. The animal findings above (uterine growth, vaginal-lining overgrowth) are the research basis for concern in people with oestrogen-sensitive conditions. These concerns come from mechanism and animal data rather than from reported harms in women.

Decisions about managing menopausal symptoms, and about any supplement alongside them, belong with a clinician.

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Does Beer Deliver 8-PN?

Beer is the main everyday source of hop prenylflavonoids (Stevens and Page, 2004), but a review of beer compounds notes that their bioavailability and any health effects from moderate beer consumption still need to be determined (Chen and colleagues, 2014). Given that 8-PN was undetectable in most people even after 180 mg of its precursor (Legette and colleagues, 2014), beer is not a meaningful or reliable source of oestrogenic activity, and the alcohol it contains carries separate risks. See Dog Poisoning, Allergy and Beer.

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What Remains Unknown

1. Whether 8-PN-standardised hop extracts reduce hot flushes in a large, long, placebo-controlled trial.
2. The dose of 8-PN needed for an effect, and how much individual metabolism changes it.
3. Effects on the breast and uterine lining with long-term use in women.
4. Whether any bone-protective effect seen in laboratory work appears in people.
5. Interactions with hormone therapy, hormone-blocking cancer drugs, or other medicines.

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Key Research Papers

1. Štulíková K, Karabín M, Nešpor J, et al. Therapeutic Perspectives of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops. Molecules (Basel, Switzerland). 2018;23(3). PubMed PMID: 29543713
2. Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry. 2004;65(10):1317-30. PubMed PMID: 15231405
3. Chen W, Becker T, Qian F, et al. Beer and beer compounds: physiological effects on skin health. Journal of the European Academy of Dermatology and Venereology : JEADV. 2014;28(2):142-50. PubMed PMID: 23802910
4. Cos P, De Bruyne T, Apers S, et al. Phytoestrogens: recent developments. Planta medica. 2003;69(7):589-99. PubMed PMID: 12898412
5. Legette L, Karnpracha C, Reed RL, et al. Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops. Molecular nutrition & food research. 2014;58(2):248-55. PubMed PMID: 24038952
6. Abdi F, Mobedi H, Roozbeh N. Hops for Menopausal Vasomotor Symptoms: Mechanisms of Action. Journal of menopausal medicine. 2016;22(2):62-4. PubMed PMID: 27617238
7. Depypere HT, Comhaire FH. Herbal preparations for the menopause: beyond isoflavones and black cohosh. Maturitas. 2014;77(2):191-4. PubMed PMID: 24314619
8. Kenda M, Glavač NK, Nagy M, et al. Herbal Products Used in Menopause and for Gynecological Disorders. Molecules (Basel, Switzerland). 2021;26(24). PubMed PMID: 34946512
9. Dietz BM, Hajirahimkhan A, Dunlap TL, et al. Botanicals and Their Bioactive Phytochemicals for Women's Health. Pharmacological reviews. 2016;68(4):1026-1073. PubMed PMID: 27677719
10. Hops. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. PubMed PMID: 30000893

PubMed Topic Searches

1. PubMed: 8-Prenylnaringenin and menopause
2. PubMed: Hop extract and hot flushes trials
3. PubMed: 8-Prenylnaringenin and the oestrogen receptor

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Connections

• Hops (Humulus lupulus) — the main page for the plant
• Hops Benefits Deep Dive — the evidence ledger
• Sleep and the Valerian Combination — the sleep trials
• Xanthohumol Research — the precursor compound
• Dog Poisoning, Allergy and Beer — safety findings
• Red Clover — an isoflavone source studied for menopause
• Red Clover Isoflavones, Hormones and Safety — the same hormone questions for another plant
• Black Cohosh — the most-studied herb for hot flushes
• Chasteberry (Vitex) — another hormone-active herb
• Menopause — the transition itself
• Hot Flashes and Night Sweats — vasomotor symptoms explained
• Breast Cancer — the hormone-sensitive condition behind the safety questions

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