Advances in Cosmetic Surgery 2 (2019) 1–10

ADVANCES IN COSMETIC SURGERY

The Latest in Cosmetic Medicine

Supplements, Hormones, and Evidence
Samantha A. Thiry, MSN, FNP-C*, Jennifer L. Walden, MD, FACS
5656 Bee Caves Road, Suite E201, Austin, TX 78746, USA

KEYWORDS
 Age-related diseases  Antiaging  Supplements  Hormone replacement therapy  Andropause  Menopause

KEY POINTS
 Provider opinions have an effect on the use of hormone replacement therapy (HRT) within practices. It is important for
providers to be educated regarding the evidence behind HRT so they may safely prescribe HRT for specific patients who
understand the risks versus the benefits. A patient-centered approach should be used with this treatment option.
 The true risks versus benefits of HRT and disease processes, such as prostate cancer and breast cancer risks, must be
presented to patients by educated providers without bias. It has been proved that provider attitudes contribute to use of
antiaging medical methods. This can, in turn, negatively affect a patient’s quality of life by not providing them with safe,
monitored, and effective treatment.
 Supplements to help prevent age-related diseases continue to be researched for their true beneficial possibilities.
Evidence exists regarding specific supplements and their chemopreventive and antioxidant properties. Cancer is an age-
related disease and many supplements are aimed at reducing the risk of its occurrence. Supplement use is a patient-
driven demand.
 Providers must become more informed about supplements by receiving appropriate education regarding the evidence so
they can give patients appropriate feed-back when patient inquiries arise.

INTRODUCTION diseases as symptoms of aging. The concept of a foun-

Patients are seeking care to stop the effects of aging not
only from an external standpoint but also from an inter-
nal standpoint. As the demand for antiaging therapy
with hormones and supplements increases, it is imper-
ative that health care providers understand the evidence
supporting proper management and information
regarding alternative treatment options with hormones
and supplements [1].
Age-related diseases continue to be researched for
prevention and optimization [2]. Antiaging specialists
use a medical framework that targets age-associated
tain of youth has been around for centuries but now,
with modern medicine and advancements in technol-
ogy, antiaging practitioners have developed as a
specialty, with the requirements of understanding dis-
eases associated with age and how to physiologically
decrease a patient’s risk of acquiring an age-related dis-
ease. Various dietary and pharmacologic interventions
have been shown to increase lifespan [3]. Also,
although aging is considered a natural life process, opti-
mization of quality of life continues to be a focus. To
meet this demand, an increasingly popular focus has

Disclosure Statement: The authors have nothing to disclose.

*Corresponding author, E-mail address: Samantha.thiry.drwalden@gmail.com

https://doi.org/10.1016/j.yacs.2019.01.001 www.advancesincosmeticsurgery.com
2542-4327/19/ © 2019 Elsevier Inc. All rights reserved. 1
2 Thiry & Walden
been geared toward preventing existing disease pro-
cesses from worsening, as well as treating disease
processes through therapeutic management with hor-
mones or supplementation [3,4].
Patients have shifted the focus of surviving to
thriving throughout their lifetime. Improving a patient’s
quality of life is an important concept in antiaging med-
icine [2]. Hormonal shifts occur during the aging pro-
cess that cause several physiologic changes and clinical
presentation of symptoms. For women, symptoms of
menopause can severely affect overall quality of life as
radical shifts and imbalances of estrogen and testos-
terone hormones occur [5]. Andropause, defined as a
continual decline in testosterone with age, affects both
men and women [5,6]. Hormone therapies are effective
in the treatment of symptoms of age-related hormonal
changes for men and women, which makes it is impor-
tant to understand the evidence regarding risk versus
benefit of the treatment prescribed. It has been proved
that many providers’ opinions on hormone therapies
are not congruent and often misinformed, causing
bias [7]. This tends to cause a lack of credibility with
specific treatment protocols. Patients can end up
suffering with symptoms of hormonal shifts and the
physiologic changes of age due to lack of appropriately
prescribed care and information regarding the true risks
versus benefits of treatment [7,8].
This article examines the multifactorial approach to
antiaging medicine with hormone replacement therapy
(HRT) and treatment using nutraceuticals to help pa-
tients achieve an improved quality of life, as well as
decrease risk for development of disease process by
optimizing their health from a physiologic evidence-
based standpoint. It examines what symptoms of aging
can be improved, as well as how aging is defined, to
improve patients’ overall quality of life. Potential risks
and benefits of HRT, as well as nutraceutical supple-
mentation, are discussed. Assessment of providers’
knowledge and the options of these types of therapies
are examined, as well as appropriate assessment and
treatment in men and in women [4–8].
Age-related diseases
Antiaging medicine is an evolving movement with the
intent to help patients decrease the development of
age-related disease, as well as improve the quality of
the normal aging process [2]. This movement has
been in place for decades but has recently become
much more advanced through research and technology.
One way to define aging is that it is the result of
continuous interaction between an individual’s genetic
makeup and environmental factors, characterized by
lifelong damage accumulation and progressive loss of
tissue and organ functionality [9]. Aging is directly asso-
ciated with an increased risk of disease development.
Common age-related diseases include neurodegenera-
tive disorders, cardiovascular disease, diabetes, osteoar-
thritis, and cancer [9]. Hypertension, high glucose,
cholesterol, and triglyceride levels are age-related risk
factors for morbidity that increase with age. The concept
of targeting age-related diseases through prevention on
a molecular level is important to understanding which
treatment methods will decrease the effects of aging,
not only from a physiologic standpoint but also from
a symptomatic standpoint [9]. Directly targeting the ag-
ing process on a molecular level versus targeting age-
related diseases or symptoms is a viable strategy
[9,10]. To slow the aging process, therapies that are
considered nonstandard, such as blood-based thera-
pies, are being prescribed and tried [9].
As patients continue to seek out ways to diminish or
decrease the effects of aging, it is important for pro-
viders to be up-to-date on current treatment options.
Hormone therapies and supplements are becoming
increasingly popular as treatment and prevention of
age-related conditions. Age-related conditions are the
leading causes of death, not only in the United States
but also worldwide. They are also the leading cause of
health care expenditures [9]. By delaying the aging pro-
cess, the delay of age-related diseases occurs. Delaying
aging, resulting in 2.2 years of additional life expec-
tance, would yield the United States $7 trillion dollars
in savings over 50 years. The target of single pathologic
conditions, such as cancer or heart disease, yields less
savings [9].
Because antiaging science has huge potential finan-
cial benefits, it has tremendous commercial opportu-
nities. Scientific breakthroughs have led to antiaging
science having a more valid reputation [9]. Provider
opinions and approaches are often skewed when it
comes to subjects such as off-label administration of
medication management [7,8]. Therefore, presenting
the evidence behind some HRT and nutraceutical
blood-based approaches of antiaging is important
when creating a patient-centered plan of care [1]. Given
the multiple genes, processes, and pathways associated
with aging, there are many opportunities to develop
pharmaceuticals to target these pathways [9]. To under-
stand the antiaging process, one must first understand
what causes aging and the specific signs and symptoms
of the aging process [2,3]. The description of aging as a
time of decline and suffering is evident because age-
related diseases often cause the physiologic decline of
a patient, in turn causing the patient to suffer [2,3].

Hormonal changes in men and women
associated with age, symptoms, and
treatment options
Age-related hormonal changes in women
A significant age-related hormonal change for women is
menopause. Menopause is used to define the natural,
systemic decrease of endogenous estrogen production
from the ovaries, caused by physiologic depletion of a
woman’s ovarian reserve [11]. This process occurs in
the aging woman and manifests as the cessation of
menses and subsequent end of fertility. In many women,
vasomotor symptoms occur, as well as other physiologic
issues. Vasomotor symptoms commonly experienced
during menopause include vaginal dryness, hot flashes,
and irregular menstrual pattern. Menopausal symptoms
can greatly affect a woman’s overall quality of life and pa-
tients will bring these to a provider’s attention in search
of relief [11,12]. A progressive decline in androgen levels
also occurs as a woman increases in age. Serum concen-
trations of testosterone in women older than the age of
50 years are approximately half of that of women in
aged 20 to 30 years [13,14]. There are several symptoms
of andropause in women, including unexplained fatigue,
low libido, and decreased sense of wellness. Testosterone
therapy has been administered to women for decades to
improve sexual dysfunction [11,15]. Female sexual
dysfunction is an issue for approximately 43% of women
18 to 59 years of age [14].
Menopause is characterized by a decreased produc-
tion of both estrogen and androgen [5,11]. It is impor-
tant to understand the process of aromatization, which
is the conversion of the body’s excess testosterone into
estrogen. Expression of aromatase is important to the
adipose tissue, skin, and bone because it slows the
rate of postmenopausal bone and collagen loss [5].
Testosterone levels decline gradually with age, rather
than showing a precipitous decrease at the menopause
transition [13]. Different typical HRT plans of care are
used in premenopausal, perimenopausal, and post-
menopausal women due to hormone shifts during
each phase of her sexual maturation [11]. Each phase
is assessed differently for risks and benefits associated
with HRT, therefore making it increasingly difficult for
a provider to manage a patient’s symptoms to improve
quality of life through HRT [11].
Female sexual dysfunction and hyposexual desire are
diagnoses that are reviewed as issues that can occur in the
premenopausal, perimenopausal, or postmenopausal
phases [12]. Some studies have shown that up to 50%
of women suffer from female sexual dysfunction. Female
sexual dysfunction is characterized by low sexual desire,
The Latest in Cosmetic Medicine 3
diminished sexual arousal, vaginal dryness, and difficulty
achieving orgasm. Some women enter into menopause
naturally, whereas others enter into menopause via surgi-
cal means such as a hysterectomy [11]. In the United
States, a national survey concluded that nearly half of
women aged 57 to 85 years experience at least 1 sexual
problem, the most common issue being low sexual
desire. There has been a landmark study performed by
Laumann and colleagues [12] that found that 32% of
women ages 30 to 39 years had low sexual desire. There-
fore, it is not only perimenopausal and menopausal
women who are seeking a solution for a decreased qual-
ity of life likely due to hormonal disruption. Understand-
ing the mechanism of action of androgens in relation to
the female body is important when considering the over-
all benefit for patients seeking relief of androgen defi-
ciency symptoms [12].
Androgen deficiency in women
The organs directly responsible for production of testos-
terone in women are the ovaries and adrenal glands,
although testosterone is also converted peripherally
from androstenedione, which is also produced in the
ovaries and adrenals [11]. Androgen deficiency in women
causes decreased lean body mass, increased body fat, thin-
ning or loss of hair, osteopenia, or osteoporosis, which
present as clinical signs. Symptoms of androgen defi-
ciency include low libido, fatigue, lack of a sense of well-
being, orgasmic dysfunction, arousal disorder, vasomotor
symptoms, insomnia, and depression [11,16].
Beta endorphins increase with testosterone levels,
causing mood-enhancing effects [5]. A woman’s quality
of life is greatly affected by a decrease in androgens, not
simply because of sex hormones. Multiple organs rely
on androgens for action such as increasing bone mass,
causing erythropoiesis, augmenting certain cognitive
behaviors, stimulating muscle growth, stimulating kid-
ney growth, and modifying the pattern of adipose tissue
deposit [5]. Interestingly, the thyroid, breast, endome-
trium, colon, lung, skin, and adrenals are all affected
because androgens have a direct effect on the tissue of
each organ [5]. Androgens may affect sexual desire,
bone mineral density, muscle mass, and strength, as
well as adipose tissue. The addition of testosterone ther-
apy in testosterone-deficient women has an effect on es-
trogen production in the brain, bone, and skin
fibroblasts, among other tissues [5].
Assessment of female androgen deficiency
Female androgen deficiency is assessed through subjec-
tive questionnaires and, therefore, a lack of objective in-
formation can cause lack of consistency between
4 Thiry & Walden
provider assessment and the treatment plan. The idea
that androgen deficiency is assessed through subjective
means causes controversy among providers [8,12]. There
have been several tools designed to screen women for
hyposexual desire disorder (HSDD) [12]. The Decreased
Sexual Desire Screener (DSDS) is a validated diagnostic
tool for generalized, acquired HSDD. The DSDS is
meant to be approximately sensitive and specific for
diagnosis of HSDD in women, independent of meno-
pausal status. The Diagnostic and Statistical Manual of
Mental Disorders, 5th edition, lists specific criteria for the
diagnosis of female sexual interest or arousal disorder;
3 out of 6 symptomatic screening assessments must be
answered with a yes for diagnosis [11].
Interpretation of laboratory data associated with
decreased available androgens for women include the
review of free and total testosterone, as well as sex
hormone-binding globulin (SHBG) [13]. Free testos-
terone is biologically available testosterone, whereas
the bioavailability of testosterone for the conversion
into estrogens depends on the levels of SHBG. In a
normal scenario, only 1% to 2% of total testosterone cir-
culates unbound. SHBG binds about 66% of total circu-
lating testosterone. The rest of testosterone circulating is
bound by albumin. It is assumed that the non–SHBG-
bound circulating testosterone is biologically active
[13]. Estrogen and thyroxine increase SHBG. Testos-
terone and glucocorticoids, growth hormone, and insu-
lin suppress SHBG. It is difficult to measure testosterone
levels in women when they are at very low levels [13].
Testosterone therapy in the aging woman
Data from several studies suggest that combined HRT-
androgen therapy may be beneficial to women who
are postmenopausal who complain of low libido
despite estrogen therapy or as monotherapy in women
who are postmenopausal with female sexual dysfunc-
tion. Studies have concluded that no significant increase
of liver enzymes or cardiovascular risk factors occurred
with the administration of testosterone therapy [11].
There are multiple forms of testosterone therapy in
various routes of administration available to women
[5]. Subcutaneous hormone implants; intramuscular
injection; and transdermal, oral, and vaginal adminis-
tration of hormone replacement are among those
offered to women in search of androgen deficiency
symptom relief [5].
Safe administration of hormone replacement
therapy for women
It is extremely important for the patient and prescriber
to understand the risks versus benefits of HRT for
women. Each individual, due to family and personal
history, have variables that are important for a provider
to consider when developing a tailored treatment plan
for the patient’s needs. Women must have an active rela-
tionship with their obstetrician-gynecologist, and docu-
mented history must be reviewed by the treating
physician [11].
Abnormal menses, hirsutism, elevated blood pres-
sure, and mood swings are some of the associated
issues that may occur during androgen therapy for
women [11].
Women, hormone replacement therapy, and
cardiovascular evidence
Notably, estrogen has antiatherosclerotic and antiin-
flammatory properties that may protect women from
cardiovascular disease development through modifica-
tion of the lipid profile [17]. It is noted that women
who are premenopausal have higher high-density lipo-
protein cholesterol and lower low-density lipoprotein
cholesterol levels compared with men, which signifi-
cantly reverses after menopause [17]. Testosterone is
known to be produced by the ovaries and some of the
female body’s testosterone is converted into estrogen,
primarily when androgen levels are higher during the
premenopausal state [5,17]. The converted estrogen
has beneficial effects on vascular endothelium and
smooth muscle tissue. Menopause and the postmeno-
pausal period may be risk factors for developing coro-
nary heart disease. Directly following menopause,
there is a hormonally related risk for the development
of hypertension, coronary artery disease, congestive
heart failure, and cerebrovascular disease, which are
also age-related diseases [2,17]. The Danish Osteopo-
rosis Prevention Study recently noted in a controlled
randomized trial that menopausal hormone therapy
can have the beneficial effect of a reduced rate of coro-
nary artery disease. Hormonal therapy may be harmful
and is not advised in the setting of preexisting coronary
disease, cerebrovascular disease, or a history of throm-
boembolic disease [11]. Hormonal therapy must be
observed for risks and benefits by the administering
provider using a patient-centered approach and individ-
ualized discussion [11,17].
Hormone replacement therapy and breast
cancer concerns
It has been reviewed that there are no valid randomized
or observational clinical studies to provide appropriate
evidence that testosterone has an influence on breast
cancer risk when added to conventional postmeno-
pausal hormone therapy [14]. This is a significant point

of information to provide to patients inquiring about
HRT [14]. Breast cancer diagnosis represents about
23% of all cancers in women. It is no surprise that it
is an important subject because it is typically an age-
related disease and is a common concern for patients
considering HRT [18]. Breast cancer incidence is
increasing worldwide. Weight gain in adulthood is asso-
ciated with an increased risk of breast cancer in post-
menopausal women. Studies suggest that weight gain
before and around menopausal age may be a
determinant for the development of breast cancer in
postmenopausal women [18]. Increasing a woman’s
testosterone level to a more optimal level has the
benefit of decreasing central visceral fat, increasing
metabolic rate, and decreasing or even treating obesity.
Testosterone also has the benefit of increasing the beta
endorphins responsible for sense of wellbeing [13]. If a
woman is feeling a better sense of wellbeing she is more
likely to be physically and sexually active [13].
Decreasing obesity risk for women before and during
menopause via testosterone therapy decreases a risk fac-
tor for the development of breast cancer [18,19]. Recent
clinical data support a role for testosterone in breast
cancer prevention [19]. Women with symptoms of hor-
mone deficiency who are treated with doses of testos-
terone alone or in combination with anastrazole via
subcutaneous implants have shown a reduced inci-
dence of breast cancer. In addition, testosterone therapy
along with anastrazole has been studied to alleviate
symptoms of hormone-deficient breast cancer survivors
and was not associated recurrent disease [19].
Studies have shown that testosterone and anastra-
zole subcutaneous implants placed in tissue surround-
ing malignant tumors significantly reduces breast
cancer tumor size. Testosterone therapy has been
reviewed and there are several supporting data that
note the direct antiproliferative, protective, and thera-
peutic effects [19].
Provider opinions of hormone replacement
therapy despite evidence
There are differing opinions regarding hormone
replacement therapies that affect not only a physician’s
willingness to prescribe but also a patient’s willingness
to use hormone replacement as a therapy. Part of this
disarray is due to a lack of protocol and continued con-
troversy about normal androgen levels in women. It is
also difficult to assess for androgen deficiency in
women because the symptomology overlaps with
several other medical diagnoses [8,11]. The provider
must rule out other complications that could be pre-
senting as risks to patient’s health. Providers’ opinions
The Latest in Cosmetic Medicine 5
have been observed via survey and it has been noted
that respondents correctly identified the risks of HRT
only 28% of the time, and 67% of providers overesti-
mated the risks and benefits of HRT.
Multiple sources of valid data suggest that combined
HRT-androgen therapy may be beneficial to women
[11]. Providers need to be educated regarding studies
that concluded that no significant increase of liver en-
zymes or cardiovascular risk factors occurred with the
administration of testosterone therapy [16].
Men and testosterone supplementation
Testosterone supplementation in the United States has
increased substantially over the years. Testosterone pre-
scriptions increased by 1700% from 1994 to 2003 and
do not show any signs of decreasing in popularity [4].
As this patient-driven popularity of testosterone supple-
mentation increases, it is important for providers to un-
derstand the signs and symptoms associated with the
decline of testosterone in the male body, as well as
appropriate treatment options and risk factors [4]. To
ignore the increased patient demand for treatment of
the associated symptoms of andropause causes skewed
perspectives regarding the true risks and benefits of HRT
for men throughout the aging process [4].
Men and andropause
Men undergoing the aging process, especially andro-
pause or the progressive decline of testosterone, often
search for symptom relief. Decreased testosterone levels
are also referred to as hypogonadism [20]. Low libido is
the symptom most associated with hypogonadism,
although erectile dysfunction, decreased muscle mass
and strength, increased total body fat, decreased bone
mineral density, anemia, gynecomastia, decreased
mental capacity, and skin and hair alterations also occur
[20]. Decreased quality of life, a diminished sense of
wellbeing, and insomnia are additional symptoms pre-
sent in androgen-deficient men. On clinical presenta-
tion, decreased muscle mass and strength, decrease in
bone mass, osteoporosis, and increased central body
fat may be noted in a patient with testosterone defi-
ciency [20,21]. When assessing for testosterone defi-
ciency, it is important for the provider to use an
approach that considers other age-related diseases by
using objective information, such as laboratory work,
to assess the patient for issues that may be present in
addition to androgen deficiency.
Testosterone deficiency is also associated with
increased cardiometabolic risk. For example, total
testosterone levels are inversely associated with risk of
cardiovascular events. Testosterone deficiency is
6 Thiry & Walden
associated with endothelium damage and testosterone
therapy enhances endothelial repair and function, and
increases synthesis and release of endothelial nitric ox-
ide in the body’s vascular system [20]. Testosterone
deficiency is associated with increased systolic blood
pressure and increased arterial stiffness, which are risk
factors that can lead to further development of age-
related diseases, such as coronary artery disease, hyper-
tension, and hypercholesterolemia [2,4,20].
Diagnosing low testosterone in men
The decline of testosterone for men is about 1% per year
after the age of 30 years and reaches a 30% decline by
the eighth decade of life [4]. The Androgen Deficiency
in the Aging Male (ADAM) questionnaire is an impor-
tant assessment tool when assessing for male androgen
deficiency. Testosterone declines as men age and the
symptoms associated with this decline cause an abun-
dance of unwanted patient symptoms that affect their
overall wellbeing [4]. Assessment regarding the subjec-
tive presence of the most commonly reported androgen
deficiency–associated symptoms must be performed by
a diagnosing provider. The symptoms associated with
this decline cause an abundance of unwanted patient
symptoms, such as fatigue and depression, and a
decreased sense of wellbeing [4]. When assessing for
the reasons for existing symptoms of hypogonadism,
it is important to check patient’s serum total testos-
terone, free testosterone, and SHBG, as well as the total
prostate-specific antigen (PSA) if appropriate for pa-
tient’s age range, when considering prescribing testos-
terone therapy [21].
Testosterone therapy benefits reported
Benefits of testosterone therapy in men include
increased libido, sexual function, bone density, muscle
mass, body composition, mood, erythropoiesis, cogni-
tion, quality of life, and decreased cardiovascular
disease. Improved sexual desire, function, and perfor-
mance are reported by men receiving testosterone
replacement therapy (TRT) [4,6,20].
The cognitive effects of androgen deficiency are asso-
ciated with decline in visual and verbal memory. Men
with higher ratios of testosterone to SHBG show a
decreased risk of Alzheimer disease. This was found in
the Baltimore Longitudinal Study of Aging, a prospec-
tive longitudinal study. It was noted that risk for Alz-
heimer disease was reduced by 26% for each 10 unit
(mmol/mmol) increase in free testosterone at 2, 5,
and 10 years. There are also well-reported data for a
strong correlation between serum levels of testosterone
and cognitive performance in mathematical reasoning
and spatial abilities [6]. Testosterone therapy in hypo-
gonadal men may have some benefit for cognitive per-
formance, especially in older men who are at an
additional risk of developing dementia or Alzheimer
because these are typically age-related diseases [6].
Glycometabolic and cardiometabolic functions, as
well as body compositions, are negatively affected by
testosterone deficiency or hypogonadism [20]. Testos-
terone and its metabolite, 5 alpha-dihydrotestosterone,
regulate energy metabolism, muscle growth, and main-
tenance and inhibit adipogenesis. An inverse relation-
ship between testosterone and insulin resistance has
been postulated and higher physiologic levels of testos-
terone seem to be protective against the development of
type II diabetes mellitus [20,21]. The prevalence of type
II diabetes mellitus and men with hypogonadism is as
high as 33% [21]. It has been shown that TRT causes
an improvement in glycemic control, as well as insulin
resistance, in men with type 2 diabetes [21]. Subcutane-
ous hormone implants, intramuscular injection, trans-
dermal, and sublingual administration of hormone
replacement are among those offered to men in search
of androgen deficiency symptom relief [6].
Safe administration: prostate cancer risk and
other testosterone replacement therapy
considerations
Prostate cancer and the role of testosterone in the disease
often results in confusion. It has not been assessed that
testosterone replacement directly causes prostate cancer,
although its administration in the presence of a carci-
noma can enhance the carcinoma present [4]. Prostate
cancer is a common, androgen-dependent cancer. There-
fore, testosterone administration is absolutely contrain-
dicated in men with clinical prostate cancer. Some men
are diagnosed with prostate cancer less than 4, therefore
establishing a baseline is important [4]. Assessing for
prostate cancer risk is important when assessing the risks
versus benefits of testosterone therapy in symptomatic,
androgen-deficient men. Data have shown that suggest
administration of testosterone in androgen-deficient
men can produce modest incremental increase in serum
PSA levels. These increments should generally be less
than 0.5 ng/mL; increases exceeding 1.0 ng/mL over 3
to 6 months are unusual. Recommendations for moni-
toring prostate-related adverse experiences during TRT
in older men include a baseline evaluation of a digital
rectal examination, serum PSA, and an AUA symptom
score for benign prostatic hypertrophy. Also, follow-up
evaluations should occur at 3, 6, and 12 months, then
annually, with review of the previously mentioned
monitoring tools [4].

Some clinicians practice safe administration of TRT
in men by performing a prostate biopsy when there is
a clinical presentation of prostate cancer risk before pre-
scription of TRT. High-grade prostatic intraepithelial
neoplasia (PIN) has been postulated to be a precancer-
ous condition [21]. An examination of prostates
removed at radical prostatectomy for prostate cancer
revealed high-grade PIN in 86% of cases. It has been
shown that there was no increased risk of prostate can-
cer in hypogonadal men with PIN treated with testos-
terone for 1 year [21]. Continued studies must be
performed for long-term analysis. To date, no study
has definitively shown a relationship between TRT
and prostate cancer. Many providers are hesitant to treat
patients for androgen deficiency owing to fear of
increasing the risk for prostate cancer, whereas evidence
does not support this clinical precaution [21]. There-
fore, prescribers refrain from prescribing TRT to men
who suffer androgen deficiency symptoms and side ef-
fects owing to presumptions that are not evidence-
based [21].
PSA levels increase with age in men regardless of
prostate cancer status, which is why proper thorough ex-
amination and evaluation with established baselines
are such important components when considering
TRT risks versus benefits of therapy [21].
Lack of consistency regarding the prescription of TRT
for men with hypogonadism leads to provider confu-
sion. During the assessment, the provider must under-
stand the process of deciding what specific symptoms
of aging need to be addressed. Androgen deficiency
symptoms commonly affect an individual’s quality of
life and vital physiologic functions [4,6]. To restore
overall wellbeing, balancing these hormones to the
levels of a younger, more youthful, and more well self
is often the goal of HRT [4,6]. It is thought that a consis-
tent decline in testosterone occurs as a direct cause of
age; therefore, restoring testosterone levels to that of a
younger age is thought to help reduce certain age-
related signs and symptoms [4,6,12,20,21]. This has
been evident because patients have had positive physi-
ologic and psychological outcomes associated with TRT.
Because of a recent paradigm shift, it is important for
providers to be educated about the true risks of therapy
and to understand when referral to a gynecologist or
urologist is an appropriate and vital component for
safe administration of TRT [13,22].
Potential risks of TRT must be discussed with the pa-
tient and informed consent of receiving this knowledge
should be documented [13]. TRT can cause erythrocyto-
sis, which in turn can have adverse cardiovascular or
neurologic events. TRT can also cause testicular atrophy
The Latest in Cosmetic Medicine 7
and infertility. Symptoms of BPH may worsen with
therapy, although they could also improve. Acne and
other skin disorders, such as hirsutism, as well as exac-
erbation of sleep apnea, may occur with TRT [20].
Nutraceuticals and antiaging
An extensive amount of research is still required to
explore the profiles and extents of the benefits that nat-
ural compounds provide, although there is increasing
evidence that a nutritional approach provides a tool
to combat age-related diseases. Senescent cells have
been identified as the cause of organismal aging. Both
natural and synthetic compounds have been suggested
to have antisenescence activities, otherwise known as
senolytics [9]. Understanding proinflammatory signals
and prooxidant signals is important to develop man-
agement with antioxidants and antiinflammatory com-
pounds for healthier aging [9]. Polyphenol-rich foods
are one of nature’s antisenescent compounds [9]. Spe-
cific types of polyphenols have properties that not
only promote cell death of aging cells but also delay
the death of healthy tissue. Many supplements use poly-
phenol extract to produce concentrated polyphenol
with the intent of health promotion for the consumer.
Antioxidant and antiinflammatory properties of poly-
phenols reduce the risk of developing age-related dis-
ease [9].
There is evidence that polyphenols contain cardio-
protective and neuroprotective functions such as the
reduction of postprandial hyperlipemia and insulin
resistance. A reduction in glucose uptake in tumor cells
induced by certain polyphenols suggests an anticancer
effect in several human cancers [9]. Although
polyphenol-rich nutrients are a source of chemopreven-
tive, antioxidant, and antiaging properties, there are
other nutrients that have been observed and are viewed
as having similar effects on the human body. The
following descriptions explore popular forms of supple-
mentation widely available and sometimes marketed
with antiaging properties. Chemopreventive and antise-
nescent properties are the focus of properties of each
nutraceutical or supplement described [9].
Curcumin
Curcumin is a polyphenol-rich source often used in the
form of a spice. Curcumin is a root also known as
turmeric or Curcuma longa. It is an ingredient that is
often used in cooking and is one of the ingredients in
curry powder. Curcuminoids are the bioactive compo-
nents of curcumin [1,9,23]. These have been of interest
for years in chemoprevention because they can inhibit
carcinogen activation by way of cytochrome enzymes.
8 Thiry & Walden
Curcuminoids also exhibit antioxidant and antiinflam-
matory properties [1,23]. There is evidence of curcu-
min’s ability to inhibit growth of cancer stem cells;
therefore, this supplement has been hypothesized to
have the potential to act as an adjunct treatment to
conventional cancer treatments, including chemo-
therapy [1].
Curcumin is poorly absorbed by the body, therefore
making therapy a challenge [1]. Much of the available
research on curcumin focuses on the prevention of colo-
rectal cancer. The thought is that because of poor ab-
sorption of curcumin by the body, the spice has direct
mucosal contact with the colorectal tract [1,23]. Curcu-
min treatment has been seen to increase the lifespan in
some animal models. Owing to the obstacle of poor ab-
sorption of its hydrophobicity and poor oral bioavail-
ability, new strategies, such as curcumin-loaded
micelles, are being explored to improve delivery of cur-
cumin to the body [9]. An important study was con-
ducted in 2006 by Cruz-Correa and colleagues in
which participants who had familial adenomatous pol-
yposis received curcumin 480 mg and quercetin 20 mg
orally 3 times a day for 9 months. Participants had an
average decrease of polyp number by 60.4% from base-
line and the mean decrease in polyp size from baseline
with treatment was 50.9%. Additional studies must be
completed to understand the true benefits of curcumin,
although there are evident benefits of supplementation
concluded from prior research [1,9,23].
Probiotics
Probiotics have received increasing popularity for
health benefits and many patients are inquiring how
they may be of benefit. Probiotics are live microorgan-
isms found in fermented foods such as yogurt and kefir.
Probiotics are found in concentrated forms in supple-
ment products [1]. Probiotics may have chemopreven-
tive benefits for the gastrointestinal tract and are of
particular interest in preventing colorectal cancers.
Lactobacillus species are commonly provided in probi-
otic supplement capsules. Bifidobacterium is another
colonized organism that proves to have gut health ben-
efits [1]. Their mechanisms of action, which are thought
to be chemopreventive, are many. Probiotics have the
ability to alter gut microbiota and, as a result, inhibit
or induce colonic enzymes that regulate growth of
harmful bacteria, which in turn benefits immune func-
tion and stimulates active anticancer metabolite pro-
duction. Yogurt is fermented milk that breeds the
organisms used in probiotic supplements. Studies in
women have found an inverse association between con-
sumption of fermented milk and breast cancer risk [1].
The EPIC Italy study followed 45,241 adults for 12 years
and found that yogurt consumption may reduce the risk
of colorectal cancer by up to 35%. This conclusion sug-
gests a promising role for probiotic organisms and the
prevention of colorectal cancer. Trials are ongoing to
research the benefits of probiotics. The chemothera-
peutic effect has also been noted in patients diagnosed
with superficial bladder cancer. Those taking oral sup-
plementation had a higher 3-year recurrence-free sur-
vival rate [1]. Increasing evidence notes that the gut
microbiota is involved in the development of human
diseases such as obesity, metabolic syndrome, diabetes,
cardiovascular disease, cancer, and neurodegenerative
disorders, which are commonly associated with age-
related diseases [1,9].
B vitamins
B vitamins continue to be researched for their necessary
role in a person’s health status and there is evidence that
supports specific physiologic functions of B vitamins. Vi-
tamins B3 (niacin), B6 (pyroxene), B9 (folate), and B12
(cobalamin) work in a synergistic fashion as water-
soluble vitamins with proven vital roles in brain and
nerve function by supporting general metabolic function
as a mechanism of action [1]. Whole grains, dairy prod-
ucts, potatoes, legumes, and bananas, as well as fish, or-
gan meats, and poultry, are commonly consumed food
sources that contain B vitamins [1]. In the United States,
as well as many other countries, B vitamins are included
as an enrichment in flour. There is some observational
evidence that has suggested the protective role of B vita-
mins against some cancers. Vitamin B3 (niacin) protects
DNA from damage when consumed in high doses. There
are also studies that show that daily supplementation of
folic acid and vitamin B12 over 2 years resulted in a
methylation of genes associated with abnormal cell
development and carcinogenesis [1]. Vitamin B9 (folate)
originates mainly in green leafy vegetables, as well as
certain fruits, and is required for DNA synthesis and
DNA methylation. The biological roles of B vitamins
continue to be explored and it is hypothesized that
they could potentially be important in cancer prevention
[18]. The protective role of B vitamins on DNA con-
tinues to be explored, including their role in breast can-
cer because protective effects have been observed in
populations with low folate status. However, more
research is needed to develop more conclusive support
for this hypothesis [18]. A randomized controlled study
completed in New Zealand and Australia showed that
daily supplementation with vitamin B3 was associated
with lower incidence of nonmelanoma skin cancers.
Research regarding B vitamins continues to be

performed and is needed to draw more conclusions
regarding B vitamin benefits to the body’s immunologic
system and their ability to support DNA in prevention of
carcinogenic effects [18].
Diindolylmethane supplement or cruciferous
vegetables
Diindolylmethane (DIM) and indole are major bioactive
molecules of cruciferous plants known to act on enzymes
responsible for the metabolism of estrogen [24]. The
most potent dietary indole is DIM because it is the
most potent estrogen blocker associated with lowering
risk of breast cancer [24]. The cancer preventative po-
tency of DIM is under clinical investigation because of
its important role of blocking estrogen via its ability to
maintain higher levels of 2-hydroxesterolne. Higher
levels of estrogens are associated with breast, uterine,
and cervical dysplasia. DIM’s ability to reduce these spe-
cific estrogens causes a reduction in clinical presentation
of breast, uterine, and cervical dysplasia. Cruciferous veg-
etables have many other physiologic functions that are
chemopreventive. DIM supplements are widely available
and used as a chemopreventive nutraceutical [24].
SUMMARY
Patients are seeking treatment options to reduce the
signs and symptoms associated with age and age-
related diseases [2]. Antiaging medicine must continue
to be explored, streamlined, researched, and better un-
derstood by providers and patients, including
decreasing risk of age-related diseases through hormone
replacement therapies and with supplements that have
proven health benefits, [1,2,10].
As the popularity of hormonal and nutraceutical
supplemental therapies increases, it becomes increas-
ingly important for providers develop better informa-
tion sets for patients and to not allow their opinions
to obscure the facts that present the benefits and risks
of supplementation and HRT. Use of HRT and supple-
ments as a means of physiologically decreasing the ef-
fects of aging must be done with proper knowledge of
the risks versus the benefits when creating an individu-
alized plan. Using a patient-centered approach, the risk
of development of several age-related disease processes
can be reduced [1]. Although much of the research
regarding TRT focuses on treatment of men, women
also substantially benefit from treatment with testos-
terone [5,6,12].
When assessing for risk factors of age-related dis-
eases, it is important to use appropriate assessment
tools and diagnostic procedures to understand when
The Latest in Cosmetic Medicine 9
appropriate referrals must be made [11]. By building
credibility through increased education of providers
regarding evidence of the benefits of dietary and nutra-
ceutical supplements, as well as HRT, patients will start
to receive the treatment of symptoms and health issues
that have a significant impact on their quality of life
[1,13]. This article examines the multifactorial approach
to antiaging medicine with treatment using HRT and
nutraceuticals to help patients achieve an improved
quality of life, as well as decrease the risk for develop-
ment of disease process by optimizing their health
from a physiologic, evidence-based standpoint. Under-
standing signs and symptoms of aging is important
when managing a patient’s quality of life through
HRT and supplementation. Potential risks and benefits
of HRT, as well as nutraceutical supplementation, must
be postulated on a case-by-case basis for the safest, most
effective approach in management by the responsible
provider. Assessment of providers’ knowledge and op-
tions of these types of therapies as appropriate treat-
ment in men and in women must continue be
explored [1,5,6,11].
REFERENCES
[1] Sanders K, Moran Z, Shi Z, et al. Natural products for
cancer prevention: clinical update 2016. Semin Oncol
Nurs 2016;32(3):215–40.
[2] Mykytyn CE. Anti-aging medicine: a patient/practitioner
movement to redefine aging. Soc Sci Med 2006;62(3):
643–53. Available at: http://ezproxy.lib.utexas.edu/
login?url5http://search.ebscohost.com/login.aspx?direct5
true&db5cmedm&AN516040177&site5ehost-live. Ac-
cessed October 30, 2018.
[3] de Magalhães JP, Stevens M, Thornton D. The business of
anti-aging science. Trends Biotechnol 2017;35(11):
1062–73.
[4] Bhasin S, Singh AB, Mac RP, et al. Managing the risks of
prostate disease during testosterone replacement therapy
in older men: recommendations for a standardized
monitoring plan. J Androl 2003;24(3):299–311. Avail-
able at: http://ezproxy.lib.utexas.edu/login?url5http://
search.ebscohost.com/login.aspx?direct5true&db5cmed-
m&AN512721204&site5ehostlive. Accessed September
12, 2018.
[5] Maia H Jr, Casoy J, Valente J. Testosterone replacement
therapy in the climacteric: benefits beyond sexuality. Gy-
necol Endocrinol 2009;25(1):12–20.
[6] Bassil N, Alkaade S, Morley JE. The benefits and risks of
testosterone replacement therapy: a review. Ther Clin Risk
Manag 2009;5(3):427–48. Available at: http://ezproxy.
lib.utexas.edu/login?url5http://search.ebscohost.com/
login.aspx?direct5true&db5cmedm&AN519707253&si-
te5ehost-live. Accessed October 1, 2018.
10 Thiry & Walden
[7] Levens E, Williams RS. Current opinions and un-
derstandings of menopausal women about hormone
replacement therapy (HRT)-the University of Florida expe-
rience. Am J Obstet Gynecol 2004;191(2):641–6. Available
at: http://ezproxy.lib.utexas.edu/login?url5http://search.
ebscohost.com/login.aspx?direct5true&db5cmedm&AN5
15343254&site5ehost-live. Accessed August 29, 2018.
[8] Williams RS, Christie D, Sistrom C. Assessment of the
understanding of the risks and benefits of hormone
replacement therapy (HRT) in primary care physicians.
Am J Obstet Gynecol 2005;193(2):551–6. Available at:
http://ezproxy.lib.utexas.edu/login?url5http://search.
ebscohost.com/login.aspx?direct5true&db5cmedm&AN5
16098892&site5ehost-live. Accessed August 29, 2018.
[9] Gurau F, Baldoni S, Prattichizzo F, et al. Anti-senescence
compounds: a potential nutraceutical approach to
healthy aging. Ageing Res Rev 2018;46(1):14–31.
[10] Janson M. Orthomolecular medicine: the therapeutic use
of dietary supplements for anti-aging. Clin Interv Aging
2006;1(3):261–5. Available at: http://ezproxy.lib.utexas.
edu/login?url5http://search.ebscohost.com/login.aspx?
direct5true&db5cmedm&AN518046879&site5ehost-
live. Accessed September 10, 2018.
[11] Swords KE. Hormone therapy for menopausal women in
the primary care setting. J Nurse Pract 2017;13(8):562–9.
[12] Khera M. Testosterone therapy for female sexual dysfunc-
tion. Sex Med Rev 2015;3(3):137–44.
[13] Davis SR, Tran J. Testosterone influences libido and well-
being in women. Trends Endocrinol Metab 2001;12(1):
33–7. Available at: http://ezproxy.lib.utexas.edu/login?
url5http://search.ebscohost.com/login.aspx?direct5-
true&db5cmedm&AN511137039&site5ehost-live. Ac-
cessed August 28, 2018.
[14] Bitzer J, Kenemans P, Mueck AO. Breast cancer risk in
postmenopausal women using testosterone in combina-
tion with hormone replacement therapy. Maturitas 2008;
59(3):209–18.
[15] Shufelt CL, Braunstein GD. Safety of testosterone use in
women. Maturitas 2009;63(1):63–6.
[16] de Paula FJF, Soares JM Jr, Haidar MA, et al. The benefits
of androgens combined with hormone replacement
therapy regarding to patients with postmenopausal sex-
ual symptoms. Maturitas 2007;56(1):69–77. Available
at: http://ezproxy.lib.utexas.edu/login?url5http://search.
ebscohost.com/login.aspx?direct5true&db5cmedm&AN5
16822626&site5ehost-live. Accessed October 29, 2018.
[17] Svatikova A, Hayes S. Menopause and menopausal hor-
mone therapy in women: cardiovascular benefits and
risks. Revista Colombiana de Cardiología 2018;25(S1):
30–3.
[18] Chajes V, Romieu I. Nutrition and breast cancer. Matur-
itas 2014;77(1):7–11.
[19] Glaser R, Dimitrakakis C. Testosterone and breast cancer
prevention. Maturitas 2015;82(3):291–5.
[20] Traish AM. Benefits and health implications of testos-
terone therapy in men with testosterone deficiency. Sex
Med Rev 2018;6(1):86–105.
[21] Rhoden EL, Morgentaler A. Testosterone replacement
therapy in hypogonadal men at high risk for prostate
cancer: results of 1 year of treatment in men with prostatic
intraepithelial neoplasia. J Urol 2003;170(6 Pt 1):
2348–51. Available at: http://ezproxy.lib.utexas.edu/
login?url5http://search.ebscohost.com/login.aspx?direct5-
true&db5cmedm&AN514634413&site5ehost-live. Ac-
cessed August 30, 2018.
[22] Patrick Selph J, Carson CC. Testosterone replacement
therapy in men with prostate cancer: what is the evi-
dence? Sex Med Rev 2013;1(3):135–42.
[23] Vemuri S, Banala RR, Subbaiah GPV, et al. Anti-cancer
potential of a mix of natural extracts of turmeric, ginger
and garlic: a cell-based study. Egypt J Basic Appl Sci
2017;4(4):332–4.
[24] Manchali S, Kotamballi N, Murthy C, et al. Patil Crucial
facts about health benefits of popular cruciferous vegeta-
bles. J Funct Foods 2012;4(1):94–106.