Student ID# 6962

LITERATURE REVIEW

What is the evidence of hops as an adjunct treatment to

finasteride in halting or reducing the progression of
prostate enlargement and its associated symptoms
in men with benign prostatic hyperplasia?

P = (Population/problem) Men with benign prostatic hyperplasia

I = (Intervention) Hops (Humulus lupulus)
C = (Comparison) Finasteride
O = (Outcome) Halting or reducing the progression of prostate
enlargement and its symptoms

This literature review investigates the evidence for hops as an adjunct treatment
to finasteride in men with benign prostatic hyperplasia (BPH) in halting or
reducing the progression of prostate enlargement and its symptoms.

Introduction
Benign prostatic hyperplasia (BPH), also known as an enlarged prostate, is a
non-cancerous disease typically occurring in men over the age of 40 and
increasing in incidence with age (Frydenberg, 2010; Elsevier, 2012). Nacey,
Morum and Delahunt (1995) from the Wellington School of Medicine, New
Zealand, reported BPH affected 13% of men aged 40-49, 22% aged 50-59,
34% aged 60-69 and 33% of men aged 70 years or older in New Zealand.
Whereas, University of Maryland Medical Center (UMMC) (2013) quotes USA
statistics of 60% of men over the age of 60 and 80% of men over the age of 80
as having BPH. As some patients are asymptomatic or reluctant to report
symptoms to their general practitioner, it is possible rates of BPH are higher
than reported above (Garraway, Collins & Lee, 1991; Lee, Chun & Lee, 2005).
Furthermore, the differences between New Zealand and USA statistics may be
historically related to nutrition, environment and culture and also due to the
increased incidence of BPH between 1995 and 2013.

Page 1 of 23
 Student ID# 6962

According to Scott and Scott (1993), health costs for the treatment of BPH as a
primary diagnosis in 1991 was estimated at NZ$16 million with the cost of lost
productivity estimated at NZ$4 million. This literature review was unable to find
any more recent data on New Zealand-based health costs relating to BPH, nor
any data for Australia. However, USA health costs relating to BPH in 2000
were US$1.1 billion dollars and included 117,000 emergency room visits,
105,000 hospitalisations and as much as 38 million hours of lost productivity
(Parsons, 2010). Parsons (2010), also states that including overactive bladder
and urinary tract infection patients, the estimated annual cost of BPH is closer
to US$3.9 billion dollars. Thus BPH has a far reaching effect into public and
private enterprise, health systems and homes worldwide.

Current research indicates that metabolic syndrome is a significant risk factor to

the development of BPH (Vignozzi, 2013; Ozden et al., 2007; Park et al., 2013).
Evidence suggests that Humulus lupulus (hops) as a herbal extract (Lerman et
al., 2008) and in hopped beer (Freiberg et al., 2004), is effective in reducing the
symptoms of metabolic syndrome. Based on this association; by reducing the
effects of metabolic syndrome, the symptoms of BPH may be averted.

This research review found no in vivo investigations on hops as a sole

treatment, nor concomitant use of hops with finasteride for this condition,
therefore the PICO question is unable to be answered. However, this literature
review will compare the evidence that was found to relating to both treatments
and consider the proposed use of hops as a sole treatment to reducing the
symptoms of BPH, as a feasible and possible intervention which requires further
research and investigation.

Search terms used: hops and benign prostatic hyperplasia, hops and BPH,
humulus lupulus and benign prostatic hyperplasia, humulus lupulus and BPH,
hops and enlarged prostate, humulus lupulus and enlarged prostate, hops and
metabolic syndrome, humulus lupulus and metabolic syndrome, beer and
metabolic syndrome, benign prostatic hyperplasia and standard care, metabolic
syndrome and benign prostatic hyperplasia, metabolic syndrome and BPH,

Page 2 of 23
 Student ID# 6962

benign prostatic hyperplasia and incidence, benign prostatic hyperplasia and

prevalence, benign prostatic hyperplasia and health costs/economic burden,
benign prostatic hyperplasia and risk factors, benign prostatic hyperplasia and
aetiology, benign prostatic hyperplasia and pathophysiology, benign prostatic
hyperplasia and signs/symptoms, benign prostatic hyperplasia and diagnosis,
hops and constituents, benign prostatic hyperplasia and complications/surgery
complications, benign prostatic hypertrophy and erectile dysfunction.

Search databases used: PubMed, Science Direct, Google Scholar, Natural

Standard, Cochrane Review, Wiley Online, Google, ClinicalTrials.gov, Medsafe,
CITES.

Benign Prostatic Hyperplasia (BPH)

The aetiology of BPH is not absolute, but most commonly the cause is regarded
as an age-related hormonal imbalance (Barral, 2005; Jamison, 2006). BPH is
characterised by a proliferation of the epithelial and stromal cells of the prostate,
(Ribal, 2013) causing prostate enlargement (figure 1).

Figure 1: Normal versus enlarged prostate (National Cancer Institute, 2008).

Page 3 of 23
 Student ID# 6962

Although the prostate does not produce any hormones, it is a hormone-

dependent gland (Barral, 2005) relying on exogenous hormones in order to
function appropriately. The prostate is sensitive to fluctuations in hormone
changes and according to Huether and McCance (2008) prostate epithelium
levels of 5-alpha reductase (5-AR) (a hormone required to convert testosterone
to dihydrotestosterone (DHT)) and DHT decrease with age, but stromal levels
remain constant. This exerts a proliferative effect on both epithelial and stromal
cells (Elsevier, 2012) and may elicit elevated levels of androgen signalling
within prostate tissue perpetuating a cycle of hypersensitivity and prostate
growth (Briganti et al., 2009).

It is the projection of the prostatic adenoma that determines the extent of

urethral obstruction and symptoms experienced, with some cases producing a
posterior projection which poses little or no symptoms (Barral, 2005). Typically
a range of lower urinary tract symptoms (LUTS) are experienced by patients
(UMMC, 2013). These can include difficulty urinating (starting, stopping or
maintaining flow), nocturia, increased frequency in urination, retention,
incontinence, discomfort, pain or urethral bleeding in extreme cases (National
Association for Continence, 2013; Elsevier, 2012). According to Hoesl, Woll,
Burkart and Altwein (2005) and Fan (2013), a less-reported and under-
diagnosed consequence of LUTS symptoms experienced by BPH patients is
erectile dysfunction. Hoesl et al. (2013) reported of 8,768 BPH patients
examined during a German study, 62% of the participants were diagnosed with
erectile dysfunction, of which 47% required treatment. Hoesl et al. (2013)
conclude that irrespective of the prevalence of erectile dysfunction in BPH
patients, they are reluctant to ask for treatment even though it has “a profound
impact on the quality of life” (p.511) indicating that BPH has a much wider
impact than is generally recognised, particularly if complications develop.

BPH is a serious disease that can lead to complications if untreated or poorly

managed. Most commonly; urinary tract infections, urinary retention and
bladder calculi (UMMC, 2013) can occur resulting in the need for additional
medical treatment and hospitalisation, with renal failure occurring rarely

Page 4 of 23
 Student ID# 6962

(Elsevier, 2012). BPH is no longer a terminal disease due to modern drug

therapy and less invasive surgical treatments which allow it to be successfully
managed (La Vecchia, Levi & Lucchini, 1995). Historical mortality rates for New
Zealand from BPH are recorded as 13 deaths from 1950-54, 4 from 1970-74, 1
from 1985-89 and 1 from 1990-91 (La Vecchia et al., 1995). The most recent
health statistics for New Zealand as listed in the Mortality and Demographic
Data 2010 did not contain any statistics for BPH and no more recent mortality
statistics were available from the New Zealand Ministry of Health.

The link between Metabolic Syndrome and Benign Prostatic Hyperplasia

A vast amount of evidence is available showing the direct correlation between
metabolic syndrome and BPH (Park et al., 2013; Kwon, Kang & Lee, 2013;
Gacci et al., 2012; Lin et al., 2012; Tewari et al., 2011; Ozden et al., 2007).
Metabolic syndrome affects a growing number of people globally, with New
Zealand results from an Auckland-based study by Gentles et al. (2007) finding
39% Pacific people, 32% Maori and 16% others. It is estimated that 35-39% of
the adult population in the USA have metabolic syndrome according to
Gorbachinsky, Akpinar & Assimos (2010). It is a multifactorial condition which
is complex in nature, consisting of several interrelated metabolic dysfunctions
(as illustrated in figure 2) including visceral adiposity, hypertension,
dyslipidaemia, insulin resistance, systemic inflammation and vascular
degeneration (Gorbachinsky et al., 2010). Based on the pathophysiology and
literature reviewed, a conceptual diagram (figure 2) has been developed to
illustrate the progression of metabolic syndrome to BPH.

Page 5 of 23
 Student ID# 6962

Figure 2: A conceptual diagram illustrating

the progression of metabolic syndrome to BPH.

From the top of figure 2, poor diet (discussed below) and stress initiate a
cascade of events which over time contribute to the development of metabolic
syndrome and lead to the progression of BPH. Considering the events on the
second line of figure 2; visceral adiposity is metabolically active producing its
own hormones, particularly oestrogen and it is this that disrupts 5-AR and
testosterone levels creating a perpetual cascade of hormonal dysregulation
within the body, leading to prostate enlargement (Hodgson & Kizior, 2010).
Additionally, insulin resistance also has a proliferative effect on sex and stress

Page 6 of 23
 Student ID# 6962

hormones producing a detrimental effect on the prostate. Whereas,

hypertension is a stress response that stimulates inflammatory hormones and
cytokines which disrupt normal cellular function both systemically and within the
prostate. As identified in figure 2, inflammation is also the linking factor in the
dyslipidaemia aspect of metabolic syndrome due to either or both excessive
intake of exogenous cholesterol or prolonged stress creating the excessive
production of endogenous cholesterol and stress hormones which initiate
inflammatory cytokines throughout the body.

Many of the conditions associated with metabolic syndrome are regarded

individually as risk factors for the development of BPH. These include; a diet
high in refined carbohydrates, polyunsaturated fats or beef products, obesity
(Elsevier, 2012), diabetes and dysfunctional glucose metabolism/insulin
resistance, abnormal sex steroid hormone levels including testosterone, DHT,
oestrogen, oestradiol, dehydroepiandrosterone (DHEAS) and lifestyle factors
such as stress and low or no physical activity (Parsons, 2010). All of these
factors contribute to both systemic inflammation and hormonal disruption which
creates cellular dysfunction within the prostate. Other factors include;
increasing age, which as discussed earlier correlates with an increase in
prostate size and is regarded as the most significant risk factor, genetics
(Elsevier, 2012), systemic inflammation and cardiovascular disease (Parsons,
2010). However, moderate alcohol consumption has been shown to be
protective of BPH whilst no alcohol or excessive alcohol appears to contribute
to the risk of developing the condition (Elsevier, 2012). It is symptomatology
that provides the necessity for diagnosis, rather than a patient’s risk factors.

A digital rectal examination and a prostate-specific antigen (PSA) test are the
two tools for diagnosis (Huether & McCance, 2008). Additionally, a transrectal
ultrasound may be performed in order to calculate the prostate-specific antigen
density (PSAD) to eliminate prostate cancer (Huether & McCance, 2008). Once
a diagnosis is confirmed, treatment is dependent of the severity of symptoms
and if mild, can result in watchful waiting (Sarris & Wardle, 2010) and if deemed
necessary by the general practitioner, drug therapy is the first choice of

Page 7 of 23
 Student ID# 6962

treatment with severe cases requiring surgery or laser treatment (UMMC,

2013).

There are two predominant classes of drugs used to treat BPH; 5-alpha
reductase inhibitors (5-ARIs) and alpha blockers (UMMC, 2013). 5-ARIs have a
3-6 month efficacy (Hodgson & Kizior, 2008) and relieve symptoms of BPH by
preventing the conversion of testosterone to DHT thus preventing and reversing
prostate growth, reducing prostate-specific antigen (PSA) levels and increasing
urinary flow (UMMC, 2013). Whereas, alpha-blockers relieve symptoms in less
than a week and work by exhibiting vasodilatory effects on smooth muscles in
the neck of the bladder and prostate thereby improving urine flow without
affecting prostate size or PSA levels (UMMC, 2013). With regards to surgical
options, these are varied and carry both short and long term complications
(UMMC, 2013) however, as recent as September 2013, a new technological
discovery has led to the development of the UroLift ® implant device, an FDA-
approved device that retracts obstructive prostate tissue from the urethra,
improving urinary output by 30% in BPH patients (Deters, 2013). UroLift ® is
regarded as a drug-free option of treatment which is performed under local
anaesthetic. The device is not currently available in New Zealand, however, for
the purposes of this review, finasteride, a 5-ARI, also sold under the name of
Proscar (UMMC, 2013), has been selected as the focus of this research.

Humulus lupulus L. (hops), Cannabaceae family

Hops are a widely cultivated, sustainable, perennial (CITES, 2013) grown in the
northern hemisphere predominantly for beer production, with the female
inflorescence harvested in late summer, then dried for use (Drink N Brew,
2013).

Through historical trial and error it has been discovered that hops were
beneficial in treating digestive complaints, insomnia (Braun & Cohen, 2010);
hysteria, neuralgia, headaches, kidney stones and topically for leg ulcers,
toothache and earache (Bone, 2003). Modern research correlates the historic

Page 8 of 23
 Student ID# 6962

uses with the therapeutic properties found in hops constituents, as illustrated in

table 1 and discussed below.

Table 1: Main Constituents and Therapeutic Actions

Constituent Type Constituent Therapeutic Actions
Flavonoid and prenylated Xanthohumol  antiandrogenic
chalcone (phenolic  antioxidant
compound)  anticarcinogenic
 antiinflammatory
(Braun & Cohen, 2010)
Flavonoid and prenylated 8-prenylnaringenin  antiandrogenic
chalcone (phenolic 6-prenylnaringenin  phytoestrogenic
compound) (Ganora, 2009)
Phloroglucinol (phenolic α-acid humulone  antibacterial
compound)  sedative (possibly)
 antioxidant (Ganora,
2009)
Phloroglucinol (phenolic β-acid lupulone  antibacterial
compound)  sedative (possibly)
 antioxidant (Ganora,
2009)
Sesquiterpene, volatile oil α-caryophyllene  anti-inflammatory
(synonum: humulene) (Ganora, 2009)

The sedative properties provided by α-acid humulone and β-acid lupulone along
with the anti-inflammatory properties provided by xanthohumol and α-
caryophyllene, support the use of hops for the modern-day and historical
treatment of anxiety, restlessness, neuralgia, headache, sleep disorders,
indigestion and dyspepsia (Bone, 2003). The antibacterial properties from α-
acid humulone and β-acid lupulone support the historical use of hops for topical
applications. Xanthohumol, 8-prenylnaringenin and 6-prenylnaringenin exhibit
the antiandrogenic qualities to effect normalcy on prostate cells and in addition,

Page 9 of 23
 Student ID# 6962

figure 3 illustrates the pharmacodynamic actions of hops as reviewed by Van

Cleemput et al. (2009) in his research, which correlates with hops as an
appropriate treatment for BPH. It is the historical use that demonstrates the
safety of hops, as stated by Keller et al. (as cited by Van Cleemput et al., 2009),
additionally, the non-regulation of hops in New Zealand by Medsafe adds
further support for its safety (Ministry of Health [MOH], 2013). Therefore, hops
is a safe, possible intervention for treating BPH.

Figure 3: Overview of important biological effects of distinct groups

of hop bitter acids (Van Cleemput et al., 2009).

After reviewing a range of research, Van Cleemput et al. (2009) concluded that
further understanding of the bioavailability, metabolism, physiological
concentrations and targets is still required. However, hops applications in the
prevention and treatment of cancer, due to the α-acids and β-acids as illustrated
in figure 3, diabetes due to the iso-α-acids and their variants, osteoporosis and
cardiovascular disease due to the combination of constituents, looks very
promising. A detailed discussion on the research reviewed relating to the
above-listed constituents and their therapeutic actions from table 1 and figure 3
can be found on pages 12-14.

To demonstrate a therapeutic benefit, recommended dosages depend on the

type of hops preparation used; infusions or decoctions require 0.5g of dried
herb taken in 150ml water/day, fluid extract (1:1) (g/mL) the required dose is

Page 10 of 23
 Student ID# 6962

0.5mL per day (Braun & Cohen, 2010), fluid extract (1:2) (g/mL) the required
dose is 1.4-3.5mL per day (Rasmussen, 2013) and to achieve a therapeutic
dose of hops from commercial beer, three 330mL bottles is required per day is
to achieve 0.5g equivalent of dried herb (I. Williams, personal communication,
December 4, 2013). Using a (1:2) fluid extract of hops, 1g of dried herb per
2mL of finished preparation (Bone, 2003), the proposed intervention is 1mL
taken three times daily to maintain blood levels and ongoing until such time as
symptoms are reduced or relieved at which time the dosage could be reduced.
Patients should be advised to keep a daily journal of fluid intake, symptoms and
toilet visits (Sarris & Wardle, 2010) to record the progress or adverse effects
experienced, bringing the journal to a follow up consultation four weeks after the
commencement of treatment which will assist in reassessing the patient’s
condition. If there is no improvement in symptoms after three months, an
alteration to the dosage should be considered in favour of an increase.

Pharmacodynamics Compared and Contrasted

Of the literature reviewed, cellular dysfunction, hormonal imbalance and
inflammation (discussed below) are presented as the key aspects of BPH
pathogenesis. Figure 3 represents a summary of this review’s findings for the
multi-factorial progression of BPH; additionally, table 2 summarises the
pharmacodynamics of both hops and finasteride.

Page 11 of 23
 Student ID# 6962

Figure 3: Summary of Disease Progression

Cellular Dysfunction
Cellular proliferation and inappropriate apoptosis (as illustrated in figure 3) are
key cellular dysfunctions of BPH of which both hops and finasteride target. The
decrease in prostate volume with finasteride is due to the inhibition of cell
proliferation in stroma and epithelial cells (Lobaccaro, 1996), whilst exhibiting an
increase in apoptosis and decrease in cell size and function (Rittmaster, 1996).
With regards to hops, Colgate, Miranda, Stevens, Bray and Ho (2006) and
Buhler, Deinzer, Ho, Miranda and Stevens (2007) studied the effects of hop-
derived xanthohumol and its oxidation product, xanthoaurenol, using human
BPH-1 (benign prostatic hyperplasia 1) and PC-3 (malignant androgen-
independent prostate cancer 3) cell lines and found both compounds inhibited

Page 12 of 23
 Student ID# 6962

proliferation and induced apoptosis in both cell lines types. Further evidence to
support the apoptotic function of xanthohumol on BPH-1 cell lines was found by
Strathmann et al. (2010). Trialling of hops in human studies would determine if
the in vitro results are transferable to live humans. Normalising cell replication
and apoptosis is the key to preventing prostate growth, however it is imperative
to return hormonal balance for this to occur.

Hormonal Imbalance
Aromatase is responsible for converting circulating androgens including
testosterone into oestradiol, the active form of oestrogen as illustrated in figure
3 (Monteiro, Faria, Azevedo & Conceicao, 2006). According to Ho, Nanda,
Chapman and Habib (2008), oestradiol exhibits a stimulatory effect upon
stromal cells in the prostate supporting the hypothesis that oestrogens may
have a contributory role in the pathogenesis of BPH. Finasteride may indirectly
inhibit aromatase levels through the reduction of 5-AR whilst several of the
prenylflavonoids from hops have been shown to directly decrease aromatase
activity in vitro, thus reducing the synthesis of oestrogens (Monteiro et al.,
2006).

5-AR is responsible for the conversion of testosterone to DHT, as shown in

figure 3, the latter of which exhibits a proliferative effect on prostate cells as well
as reducing apoptosis. Finasteride has been successfully proven through
research and historical use to inhibit 5-AR. Hops has been shown to exhibit
antiandrogenic effects in vitro and in in vivo animal studies. Xanthohumol
(Braun & Cohen, 2010), 8-prenynaringenin and 6-prenylnaringenin (Ganora,
2009) are the three main compounds to exhibit this effect and to influence DHT
in men. The regulation of androgens and formation of DHT will regulate cell
cycles, replication, apoptosis and cell signalling preventing inflammation and
prostate growth.

Inflammation
Inflammatory cytokines cause a cascade effect upon cells inducing cellular
proliferation, disrupting cell cycles and apoptosis and altering gene expression,

Page 13 of 23
 Student ID# 6962

as illustrated in figure 3. Nuclear factor kappa B (NFkB) is required for immune

and apoptosis modulation (Colgate et al., 2006) and is an inflammatory
mediator (Snyder, 2007), responsible for modulating cyclooxygenase-2 (COX2)
and prostaglandin E2 (PGE2), both of which are inflammatory cytokines (Lin et
al, 2013). Finasteride may exhibit an indirect effect on reducing NFkB through
inhibiting 5-AR, however no evidence was found at the time of this review to
specifically correlate with this statement. Xanthohumol and xanthoaurenol from
hops have been found to induce cell cycle changes and inhibit NFkB activity in
BPH-1 cells (Colgate et al, 2006). Furthermore, according to Langezaal (as
cited by Van Cleemput et al, 2009) humulone inhibits the DNA-binding of NFkB
thus reducing the inflammatory cascade.

Furthermore, NFkB induces the release of nitric oxide, inducible nitric oxide
synthase, tumour necrosis factor alpha (TNFa), interleukin 6 (IL-6) and
interleukin 1 beta (IL-1B) which mediate inflammation (figure 3) (Trickey, 2011).
The relationship between these substances is complex with TNFa being
stimulated by either NFkB or IL-1B and yet TNFa can stimulate the production
of NFkB (Trickey, 2011, Van Cleemput et al, 2009). Furthermore, according to
Zhao, Nozawa, Daikonnya, Kondo and Kitanaka (2003), nitric oxide is
implicated in numerous inflammatory processes and in carcinogenesis.
Finasteride exhibits an indirect ability to lower nitric oxide levels through
reducing 5-AR and DHT of which the latter mediates of the production of nitric
oxide and its associated substances (Canguven, 2008). Xanthohumol along
with other hops-derived chalcones have been found to reduce nitric oxide
production directly, thereby inhibiting inducible nitric oxide synthase (iNOS)
(Zhao et al, 2003). The possible mechanism for nitric oxide’s part in
carcinogenesis may be its vasodilatory effects allowing for greater
angiogenesis. In summary, a reduction in all inflammatory mediators will
improve cell cycles, normalise cellular replication and apoptosis thereby
inhibiting prostate enlargement and the progression of BPH. Table 2 below
illustrates a comparison of the pharmacodynamics discussed above, with hops
demonstrating a greater range of effects beneficial to BPH.

Page 14 of 23
 Student ID# 6962

Table 2: Summary Comparison of Pharmacodynamics

Hops Finasteride
Inhibits cellular proliferation Inhibits cellular proliferation
Increases apoptosis Increases apoptosis
Normalises cell cycle Normalises cell cycle
Inhibits 5-AR Inhibits 5-AR
Decreases DHT Decreases DHT
Decreases aromatase No evidence found to show a
decrease in aromatase, however
finasteride is likely to indirectly reduce
aromatase
Decreases NFkB No evidence found to show a
decrease in NFkB, however finasteride
is likely to indirectly reduce NFkB
Decreases nitric oxide and iNOS Indirectly decreases nitric oxide and
iNOS

Whilst finasteride exhibits many of the same pharmacodynamics as hops as

demonstrated in table 2, hops can demonstrate a considerably longer
therapeutic history than finasteride, with a safer and less toxic profile.
Finasteride has been shown to exhibit some serious side effects including;
gynecomastia, decreased libido, erectile dysfunction, reduced volume of
ejaculate and lowered libido (Hodgson & Kizior, 2008). Additionally, according
to UMMC (2013), in 2011 the Food and Drug Administration revised the label of
finasteride to include a warning of an increased risk of high-grade prostate
cancer, in comparison hops are generally regarded as safe if taken within the
recommended dosage (Bone, 2003). Toxicity is unknown (Braun & Cohen,
2010; Bone, 2003) and may depend on preparation type. However, excessive
hops intake can lead to drowsiness (Braun & Cohen, 2010) and Ulbricht and
Seamon (2010) state hops may exhibit an agonist or antagonist effect on
hormone-dependent cancers or conditions due to its phytoestrogen content
having undetermined consequences, nonetheless in terms of BPH, the
evidence discussed above demonstrates hops safety in relation to the hormonal
and other affected factors. With regards to adverse effects, finasteride may
cause; hypersensitivity reaction, circumoral swelling and testicular pain with
unknown toxicity (Hodgson and Kizior, 2008), with semen exposure from

Page 15 of 23
 Student ID# 6962

finasteride-treated patients listed as a contraindication as it may cause birth

defects. In comparison, caution should be exercised in prescribing hops to
patients who exhibit depression (most likely due to the sedative effect), or are
pregnant, due to the undetermined actions of the phytoestrogen content of hops
(Braun & Cohen 2010). Additionally, finasteride is thought to interact with St
John’s Wort decreasing concentration and saw palmetto should be avoided due
to inadequate studies and unknown effects (Hodgson & Kizior, 2008). In
contrast, Braun and Cohen (2010) state that hops may induce or inhibit
medications sharing the CPY enzyme pathway diminishing treatment or risking
overdose. Furthermore, there is a lack of evidence to determine the
pharmacokinetics of hops (Ulbricht & Seamon, 2010) whereas finasteride is
absorbed in the gastrointestinal tract, protein-bound and metabolised by the
liver with excretion typically through faces (Hodgson & Kizior, 2008). In
summary, the evidence for hops demonstrates a broader range of benefits for
the patient with fewer side effects and shows its effectiveness in treating
metabolic syndrome, a pre-cursor to BPH.

Other Supporting Evidence:

Hops as a Treatment for Metabolic Syndrome, a precursor to BPH
Hops have been shown to reduce the symptoms of metabolic syndrome when
combined with a modified Mediterranean-style diet. Lerman et al. (2008)
studied 49 people with metabolic syndrome in a 12-week randomised, two-arm
trial in which 44 people completed at least eight weeks of the study and 41
people finished the 12 weeks. Both arms were given the same dietary and
exercise guidelines with one group receiving an additional soy protein, rho iso-
alpha acid (hop-derived: 150mg per day) and acacia proanthocyanidin (PED)
supplement.

The results at the conclusion of the study showed a resolution of metabolic

syndrome in 43% of the PED group versus 22% of the non-supplemented
group, with 5.9kg versus 5.7kg respectively per person in weight loss. Greater
reductions in cholesterol markers were found in the PED group along with
increased high density lipoprotein (HDL) (P<0.05), decreased triglyceride to

Page 16 of 23
 Student ID# 6962

HDL ratio (P<0.01), 42.7% average reduction in the PED group compared to
17.6% in the non-supplemented group. Reductions resulted in a drop in systolic
blood pressure (BP) from 129.7mm Hg at baseline to 123.4mm Hg at 12 weeks
in the PED group (P=0.025) and diastolic BP from 87.0mm Hg at baseline to
82.0mm Hg (P=0.005). Only systolic BP reduced in the non-supplemented
group. This study provides evidence that a supplement containing hops is
effective in improving the metabolic markers of metabolic syndrome patients
when combined with a Mediterranean diet. Metabolic syndrome is a pre-cursor
to BPH and this research could provide some evidence for the prevention of
BPH, however additional research is required with a greater number of
volunteers set in the New Zealand environment and without any dietary
changes to determine if supplementation alone is effective.

Conclusion
There is a lack of human studies with hops as a sole treatment or used
concomitantly with drug therapy in the treatment of BPH. Further research as
mentioned above could be performed with patients at the ‘watchful waiting’ or
early-stage BPH which is typically untreated, however recruiting general
practitioners to make such a recommendation to their patients will be difficult
due to the lack of human studies as evidence. The above evidence
demonstrates that hops contain many constituents that exhibit the required
therapeutic effects at a cellular level that are beneficial for BPH. Reducing
metabolic syndrome will reduce the incidence of BPH and lessen the
complications and health costs that are associated with both diseases. Hops
may provide a suitable intervention as a preventative or treatment for a range of
diseases from metabolic syndrome through to BPH.

From a naturopathic and holistic perspective, the clinical application of hops

could be used in conjunction with dietary and lifestyle advice and where a client
is medicated, with the notification and support of the patient’s general
practitioner.

Page 17 of 23
 Student ID# 6962

References
Barral, J. (2005). Manual therapy for the prostate. West Palm Beach, Florida,
USA: North Atlantic Books.
Bone, K. (2003). A clinical guide to blending liquid herbs: Herbal formulations
for the individual patient. St Louis, Missouri, USA: Churchill Livingstone.
Braun, L., & Cohen, M. (2010). Herbs & natural supplements; An evidence-
based guide. (3rd ed.). Chatswood, NSW, Australia: Churchill Livingstone.
Briganti, A., Capitanio, U., Suardi, N., Gallina, A., Salonia, A., Bianchi, M., …
Montorsi, F. (2009). Benign prostatic hyperplasia and its aetiologies.
European Association of Urology, 8, 865-71.
doi:10.1016/j.eursup.2009.11.002.
Buhler, D., Deinzer, M., Ho, E., Miranda, C., & Stevens, J. (2007). Patent No.
US20080233221 A1. Oregon, USA: United States Patent and Trademark
Office.
Canguven, O., & Burnett, A. (2008). The effect of 5 a-reductase inhibitors on
erectile function. Journal of Andrology, 29(5), 514-23. doi:
10.2164/jandrol.108.005025.
Colgate, E., Miranda, C., Stevens, J., Bray, T., & Ho, E. (2006). Xanthohumol,
a prenylflavonoid derived from hops induces apoptosis and inhibits NF-
kappaB activation in prostate epithelial cells. Cancer Letters, 246(1-2),
201-9. doi:10.1016/j.canlet.2006.02.015.
Deters, L. (2013). Benign prostatic hypertrophy. Retrieved from
http://emedicine.medscape.com/article/437359-overview.
Drink N Brew. (2013). Hops. Retrieved from http://drinknbrew.com/hops.html.
Elsevier. (2012). Benign prostatic hyperplasia. Retrieved 16 November 2013
from https://www.clinicalkey.com/topics/urology/benign-prostatic-
hyperplasia.html.
Fan, Y. (2013). Benign prostatic hyperplasia and erectile dysfunction: an
update. National Journal of Andrology, 19(6), 572-5. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/23862240.
Freiberg, M., Cabral, H., Heeren, T., Vasan, R., Curtis-Ellison, R., & Third
National Health and Nutrition Examination Survey. (2004). Alcohol
consumption and the prevalence of the metabolic syndrome in the US.: a

Page 18 of 23
 Student ID# 6962

cross-sectional analysis of data from the Third National Health and

Nutrition Examination Survey. Diabetes Care, 27(12), 2954-9. Retrieved
from http://www.ncbi.nlm.nih.gov/pubmed/15562213.
Frydenberg, M. (2010). Prostate enlargement (BPH) fact sheet [Brochure].
Clayton, Victoria, Australia: Monash Medical Centre.
Gacci, M., Santi, R., Nesi, G., Sebastianelli, A., Giannessi, C., Giancane, S.,
…Maggi, M. (2012). Metabolic syndrome can be related to the
development of prostatic inflammation in men with benign prostatic
hyperplasia. European Urology Supplements, 11(1), e119.
doi:10.1016/S1569-9056(12)60118-3.
Ganora, L. (2009). Herbal constituents: Foundations of phytochemistry.
Louisville, Colorado, USA: Herbalchem Press.
Garraway, W., Collins, G., & Lee, R. (1991). High prevalence of benign
prostatic hypertrophy in the community. Lancet, 338(8765), 469-71.
Retrieved from http://kan.or.kr/new/kor/sub3/filedata/200508/1508.pdf.
Gentles, D., Metcalf, P., Dyall, L., Sundborn, G., Schaaf, D., Black, P.,
…Jackson, R. (2007). Metabolic syndrome prevalence in a multicultural
population in Auckland, New Zealand. The New Zealand Medical Journal,
120(1248). Retrieved from http://journal.nzma.org.nz/journal/120-
1248/2399/.
Gorbachinsky, M., Akpinar, H., & Assimos, D. (2010). Metabolic syndrome and
urologic diseases. Reviews in Urology, 12(4), e157-80. doi:
10.3909/riu0487.
Ho, C., Nanda, J., Chapman, K., & Habib, F. (2008). Oestrogen and benign
prostatic hyperplasia: effects on stromal cell proliferation and local
formation from androgen. Journal of Endocrinology, 197(3), 483-91. doi:
10.1677/JOE-07-0470.
Hoesl, C., Woll, E., Burkart, M., & Altwein, J. (2005). Erectile dysfunction (ED)
is prevalent, bothersome and underdiagnosed in patients consulting
urologists for benign prostatic syndrome (BPS). European Urology, 47(4),
511-517. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15774251.
Hodgson, B., & Kizior, R. (2008). Saunders nursing drug handbook 2008. St
Louis, Missouri, USA: Elsevier.

Page 19 of 23
 Student ID# 6962

Huether, S., & McCance, K. (2008). Understanding pathophysiology; 4th

edition. St Louis, Missouri, USA: Mosby Elsevier.
Jamison, J. (2006). Clinical guide to nutrition and dietary supplements in
disease management. Bundoora, Australia: Churchill Livingstone.
Kwon, H., Kang, H & Lee, J. (2013). Relationship between predictors of the
risk of clinical progression of benign prostatic hyperplasia and metabolic
syndrome in men with moderate to severe urinary tract symptoms.
Urology, 81(6), 1325-9. doi: 10.1016/j.urology.2013.01.042.
La Vecchia, C., Levi, F., & Lucchini, F. (1995). Mortality from benign prostatic
hyperplasia: worldwide trends 1950-92. Journal of Epidemiology &
Community Health, 49, 379-84. doi:10.1136/jech.49.4.379.
Lee, E., Chun, K., & Lee, Y. (2005). Benign prostatic hyperplasia in
community-dwelling elderly in Korea. Journal of Korean Academy of
Nursing, 35(8), 1508-1513. doi:10.4040/jkan.2010.40.2.287.
Lerman, R., Minich, D., Darland, G., Lamb, J., Schiltz, B., Babish, J., …Tripp,
M. (2008). Enhancement of a modified Mediterranean-style, low glycemic
load diet with specific phytochemicals improves cardiometabolic risk
factors in subjects with metabolic syndrome and hypercholesterolemia in a
randomised trial. Nutrition & Metabolism, 5(29), 1-14. doi:10.1186/1743-
7075-5-29.
Lin, C., Hseih, H., Shih, R., Chi, P., Cheng, S., & Yang, C. (2013). Up-
regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-KB
pathway in mouse brain microvascular endothelial cells. Cell
Communication & Signalling, 11(8). doi: 10.1186/1478-811X-11-8.
Lin, K., Chu, H., Chen, H., Wang, T., Chiang, Y., Liu, K., & Wang, H. (2012).
Metabolic syndrome is an independent risk factor for benign prostatic
hyperplasia. European Urology Supplements, 11(1), e120. doi:
10.1016/S1569-9056(12)60119-5.
Lobaccaro, J., Boudon, C., Lechevallier, E., Mottet, N., Rebillard, X., Lumbroso,
S., …Sultan, C. (1996). Effect of finasteride (Proscar) on the proliferation
of cultured epithelial and stromal cells from normal and hyperplastic
human prostates. Cellular & Molecular Biology, 42(4), 511-8. Retrieved
from http://ncbi.nlm.nih.gov/pubmed/8828906.

Page 20 of 23
 Student ID# 6962

Monteiro, R., Faria, A., Azevedo, I & Conceicao, C. (2006). Modulation of

breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus
L.) flavonoids. Journal of Steroid Biochemistry & Molecular Biology,
105(2007), 124-30. doi: 10.1016/j.jsbmb.2006.11.026.
Nacey, J., Morum, P., & Delahunt, B. (1995). Analysis of the prevalence of
voiding symptoms in Maori, Pacific Island, and Caucasian New Zealand
men. Urology, 46(4), 506-11. Retrieved 2 October 2013 from
http://www.ncbi.nlm.nih.gov/pubmed/7571219.
National Association for Continence (NAFC). (2013). Enlarged prostate
(benign prostatic hyperplasia). Retrieved 21 September 2013 from
http://www.nafc.org/bladder-bowel-health/men-s-health/enlarged-prostate/.
National Cancer Institute. (2008). Benign prostatic hyperplasia. Retrieved
from https://visuals.nci.nih.gov/details.cfm?imageid=7137.
Ministry of Health. (2013) Search: humulus lupulus. Retrieved from
http://www.medsafe.govt.nz/searchResults.asp?q=humulus+lupulus.
Ozden, C., Ozdal, O., Urgancioglu, G., Koyuncu, H., Gokkaya, S., & Memis, A.
(2007). The correlation between metabolic syndrome and prostatic growth
in patients with benign prostatic hyperplasia. European Urology, 51(1),
199-206. Retrieved from http://ezproxy-
mc.mywisenet.com.au:2051/science/article/pii/S0302283806006579.
Park, Y., Kim, S., Kwon, H., Kang, H., Cho, K., Lee, K., …Lee, J. (2013). The
relationship between lower urinary tract symptoms/benign prostatic
hyperplasia and the number of components of metabolic syndrome.
Urology, 82(3), 674-679. Retrieved from http://ezproxy-
mc.mywisenet.com.au:2051/science/article/pii/S0302283806006579.
Parsons, J. (2010). Benign prostatic hyperplasia and male lower urinary tract
symptoms: Epidemiology and risk factors. Current Bladder Dysfunction
Reports, 5(4), 212-218. doi:10.1007/s11884-010-0067-2.
Rasmussen, P. (2013). Phytomed dosage chart – fluid extracts & tinctures
[Brochure]. Auckland, New Zealand: Phytomed Medicinal Herbs.
Ribal, M. (2013). The link between benign prostatic hyperplasia and
inflammation. European Urology, 12, 103-109. doi:
10.1016/j.eursup.2013.08.001.

Page 21 of 23
 Student ID# 6962

Rittmaster, R., Norman, R., Thomas, L., & Rowden, G. (1996). Evidence for
atrophy and apoptosis in the prostates of men given finasteride. Journal
of Clinical Endocrinology & Metabolism, 81(2), 814-9. doi:
10.1210/jc81.2.814.
Sarris, J., & Wardle, J. (2010). Clinical naturopathy: An evidence-based guide
to practice. Chatswood, NSW, Australia: Churchill Livingstone.
Scott, W., & Scott, H. (1993). Annual costs of benign prostatic hyperplasia in
New Zealand. Pharmacoeconomics, 4(6), 455-68. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/10151048.
Snyder, E.A. (2007). Beta2-adrenergic receptor modulation of macrophage
inflammatory mediator production (Dissertation). The University of North
Carolina at Chapel Hill, North Carolina, USA.
Strathmann, J., Klimo, K., Sauer, S., Okun, J., Prehn, J., & Gerhauser, C.
(2010). Xanthohumol-induced transient superoxide anion radical
formation triggers cancer cells into apoptosis via a mitochondria-mediated
mechanism. Journal of the Federation of American Societies for
Experimental Biology, 24(8), 2938-50. doi:10.1096/jf.10-155846.
Tewari, R., Prabhat, M., Natu, S., Dalela, D., Goel, A., Goel, M., & Tandon, P.
(2011). Association of benign prostatic hyperplasic (BPH) with the
metabolic syndrome (MS) and its components – ‘a growing dilemma’.
Journal of Men’s Health, 8(1), 66-71. doi: 10.1016/j.jomh.2010.09.231.
Trickey, R. (2011). Women, hormones & the menstrual cycle. Fairfield,
Victoria, Australia: Trickey Enterprises.
Ulbricht, C., & Seamon, E. (Eds). (2010). Natural standard herbal
pharmacotherapy. St Louis, Missouri, USA: Mosby Elsevier.
University of Maryland Medical Center. (2013). Benign prostatic hyperplasia.
Retrieved on 2 October 2013 from
http://umm.edu/health/medical/reports/articles/benign-prostatic-
hyperplasia.
Van Cleemput, M., Cattoor, K., De Bosscher, K., Haegeman, G., De Keukeleire,
D., & Heyerick, A. (2009). Hop (Humulus lupulus)-derived bitter acids as
multipotent bioactive compounds. Journal of Natural Products, 72, 1220-
30. doi:10.1021/np800740m.

Page 22 of 23
 Student ID# 6962

Vignozzi, L., Gacci, M., Cellai, I., Sebastianelli, A., Salvi, M., Santi, R., …Maggi,
M. (2013). Metabolic syndrome is correlated with prostatic inflammation
in men with severe LUTS related to benign prostatic hyperplasia: Results
of a preclinical and clinical experimental study. European Urology
Supplement, 12(1), 411-2. doi: 10.1016/S1569-9056(13)60896-9.
Zhao, F., Nozawa, H., Daikonnya, A., Kondo, K., & Kitanaka, S. (2003).
Inhibitors of nitric oxide production from hops (humulus lupulus L.).
Biological & Pharmaceutical Bulletin, 26(1), 61-65. doi:
10.1248/bpb.26.61.

Page 23 of 23