TESTOSTERONE THERAPY IN MEN--- AND IN WOMEN?

JERALD BAIN MD FRCPC

PROFESSOR EMERITUS

DIVISION OF ENDOCRINOLOGY AND METABOLISM

DEPARTMENT OF MEDICINE

UNIVERSITY OF TORONTO

ONTARIO COLLEGE OF FAMILY PHYSICIANS

ASA 51

NOVEMBER 28, 2013

November 28,2013

Faculty/Presenter Disclosure

• Faculty: Jerald Bain MD• Program: 51st Annual Scientific Assembly

• Relationships with commercial interests:– Advisory Consultancy Teleconference – Actavis Specialty

Pharmaceuticals Co. – Chief Medical Officer, United Paragon Associates Inc. small

R and D (non-testosterone) pharmaceutical company.

Disclosure of Commercial Support

• This program has received financial support [ organization name] from in the form of [describe support here – e.g. an educational grant]. No financial support received.

• This program has received in-kind support from [organization name] in the form of [describe support here – e.g. logistical support].None received.

• Potential for conflict(s) of interest:– Dr. Jerald Bain will discuss testosterone in this program. No

testosterone company has participated in any way in the structure, creation or financing of this lecture.

Mitigating Potential Bias

• None.

• Please note: the use of testosterone in women is off-label.

WHAT WOULD YOU DO WITH A MID TO OLDER AGE SYMPTOMATIC MAN WITH

A LOW OR LOWISH TESTOSTERONE LEVEL?

(OTHER CAUSES RULED OUT)

MR.M.-56 YEAR OLD MAN

COMPLAINTS GO BACK 3-4 YEARS: FATIGUE DECREASED STRENGTH DECREASED CONCENTRATION OSTEOPOROSIS IRRITABILITY RESTLESS SLEEP SOAKS PYJAMAS WITH SWEATS

MR.M

LH----2.6 IU/L (1.0-8.0) FSH---10.0 IU/L (1.0-10.0) T-------26.0 NMOL/L (10.0-28.0) BIO-T-3.71 NMOL/L (2.0-8.6)

PSA----0.64 MCG/L (0.0-4.0) Hb------125 G/L (132-170)

MR.M—Rx---T:200 MG.IM Q 2 WEEKS

“EMOTIONALLY I FEEL A WHOLE LOT BETTER - JUST FEELING GOOD “

“DIDN’T REALIZE WHAT MY MOOD WAS - PEOPLE COMMENT”

“SEX DRIVE HAS RE-APPEARED”“IT’S REALLY GOOD”“I FEEL BETTER

PSYCHOLOGICALLY”HOT FLASHES GONESLEEPS THROUGHT THE NIGHTLESS ACHYMORE PHYSICALLY ACTIVE“I LOOK FORWARD TO MY

INJECTION”

BEST PERIOD—DAY 2-10“I’VE BECOME AWARE OF MY

PENIS BEING THERE - IT’S A WONDERFUL REASSURING FEELING”

“I FEEL BETTER THAN I HAVE IN 20 YEARS”

WIFE DELIGHTED — MORE PHYSICAL ACTIVITY, BETTER SEX

IMPROVED ORGASMS

Hb—139 (PREVIOUSLY 125)T DOSE INCREASED TO 300

MG.Q2 WEEKS (b/o fall-off at day 10)

TESTOSTERONE MEASUREMENT

Free, 2%

*SHBG-bound, 44%

Albumin-bound, 54%

Bioavailable testosterone

Total Testosterone

Dhindsa et al. J Clin Endocrinol Metab 2004;89(11) 5462-5468.

*SHBG – sex hormone-binding globulin

TESTOSTERONE-DIURNAL VARIATION

nm

ol/L

8

6

4

2

18-29 30-49 50-59 60-69 70-79

Age (years)

80-89 90-100

7

5

3

1

TT

BT

INFLUENCE OF AGEON TESTOSTERONE

FREQUENCY OF TESTOSTERONE DEFICIENCY IN MEN OVER 50

ESTIMATES :

1. 0.5% (HAMEED, CURR OPIN INVEST DRUGS.2003;4:1213-1219)

2. 50% (ARAUJO, JCEM. 2007;93:4241-4247)

3. 20% (HEINEMAN, J ENDOCRINOL INVEST. 2005;28:34-38)

CARRUTHERS, THE AGING MALE. 2009;12:21-28

CAUSES OF BIOLOGICALLY AVAILABLE TESTOSTERONE AS MEN

AGE:

PRIMARY

HYPOGONADISM

SECONDARY

HYPOGONADISM

SEX HORMONEBINDING GLOBULIN

(SHBG)

Decreased number of Leydig cells

Decreasedpulse amplitude and frequency of LH,FSH

Decreased bio-T

Mailhot J. J Sex Reprod Med 2001.

PRESENTATION OF ANDROGEN DEFICIENCY IN AGING MEN

Frailty Fatigue Decreased energy

and work capacity Decreased muscle

strength and mass Decreased motivation

Decreased self-confidence

Irritability Increased abdominal fat Fractures and back pain

(osteoporosis) Decreased sexual

desire Erectile dysfunction

VARIABLE SENSITIVITY OF DIFFERENT TESTOSTERONE TARGETS

1.Fat accumulation begins ---- T= 10.41-12.18 nmol/l

2.Decreased lean mass, thigh muscle area, muscle strength-T=<6.94nmol/L

3.ED and libido – progressively decline as T declines

4.Role of estradiol in libido:

When T = 6.94-13.88 nmol/L

- libido 13% if estradiol ≥ 36.71 pmol/L

- libido 31% if estradiol < 36.71 pmol/L

Finkelstein. NEJM 2013;369:1011-1022

LOW TESTOSTERONE: INCREASING PREVALENCE OF SYMPTOMS

Overview of symptom-specific concentrations of total testosterone levels below which the prevalence of the respective symptom starts to increase, hence, a lack of androgens exerts influence

Total testosterone nmol/L Patients (n)

20

15

12

10

8

0

74

69

84

65

67

75

Loss of libido p < 0.001

Loss of vigour p < 0.001

Hot flushes p < 0.001

Erectile dysfunction p < 0.001

Obesity p < 0.01

Feeling depressed p = 0.001Disturbed sleep p = 0.004Lacking concentration p = 0.002Diabetes mellitus type 2 p < 0.001

Zitzmann et al. J Clin Endocrinol Metab 2006;91:4335-4343.

THE MANY FACES OF TESTOSTERONE

CLASSICAL HYPOGONADISM

ANDROPAUSE IN WOMEN BONES MUSCLES LIBIDO ERECTILE FUNCTION COGNITION MOOD

ANEMIA CORONARY ARTERY

DISEASE OBESITY DIABETES MELLITUS METABOLIC SYNDROME HIV APATHY OF PARKINSONISM AUTOIMMUNE DISEASE NARCOTIC DEPENDENCE

BAIN. Clinical Interventions in Aging. 2007;2(4): 1–10

REDUCED TESTOSTERONE CONCENTRATIONS IN MEN ARE FOUND IN

ASSOCIATION WITH:

TYPE 2 DIABETES MELLITUS

METABOLIC SYNDROME

CAROTID INTIMA-MEDIA THICKNESS

LOWER LIMB ARTERIAL DISEASE

AORTIC ATHEROSCLEROSIS

INCREASED STROKE AND TIA’s

EARLIER MORTALITY

YEAP, JCEM. 2009;94:2353-2359

TRT IN INSULIN RESISTANCE

1. Leydig cell T production insulin resistance

2. TRT reverses insulin resistance within a few days

Pitteloud. JCEM.2005;90:2636-2641Pitteloud. Diabetes Care. 2005;28:1636-1642

TESTOSTERONE AND METABOLIC SYNDROME IN MEN WITH ED

WITH HYPOGONADISM – 92.3% INSULIN RESISTANCE

WITHOUT HYPOGONADISM – 25% INSULIN RESISTANCE

Guay. J Sex Med.2007;4:1046-1055

FREQUENT OCCURRENCE OF HYPOGONADOTROPIC HYPOGONADISM IN TYPE 2 DIABETES

Percentage of hypogonadal (low FT or cFT) patients with type 2 diabetes in age groups ranging from 40–79 yr.

DANDONA. JCEM, Vol. 89, No. 11 5462-5468

% H

ypog

onad

al

0

10

20

30

40

50

60

40-49 50-59 60-69 70-79

n=28 n=37 n=13n=8

Age Range

LIFESTYLE CHANGE AND MOBILITY IN OBESE ADULTS WITH TYPE-2 DIABETES

loss of mobility with aging in DM-2 mobility leads to: independence - compromised glucose storage and clearance quality of life

mobility exists: -in obesity -with physical activity

DM-2 – twice as much disability in mobility-related activities compared to non-diabetics

REJESKI. NEJM 2012;366:1209-1217

Effect of Testosterone on Skeletal Muscle

Protein synthesis

Protein degradation

Satellite cell replication and activation

Lean body mass

Muscle cross section area

Strength

Skeletal Muscle• With aging, muscles undergo atrophy and cell loss.

• Because of their limited ability to regenerate, this leads to: a reduction in mass and

strength (sarcopenia), impaired function frailty and an increased risk of falling

• Cause is multifactorial – reductions in activity, nutrition, testosterone,

growth hormone (IGF-1), growth factors

TESTOSTERONE ACTION IN MUSCLES

Growth hormone ( GH ) increases muscle size via circulating IGF-1 levels

Testosterone increases GH production rates (via aromatization to estradiol)

Testosterone increases intramuscular levels of IGF-1

Testosterone promotes satellite cell recruitment greater # of myonuclei and larger myocytes

Testosterone promotes protein synthesis

Net result – Testosterone increases muscle size

(Fiorini 1985; Link et al, 1986; Liu et al,1987; Urban et al, 1995; Perrone et al, 1995; Blackman et al, 2002; Brill et al, 2002; Svensson et al, 2003; Herbst and Bhasin,2004; Sinha-Hikim et al, 2006)

DECREASE IN ABILITY OF AGING MEN TO PLAY SPORTS RELATED TO

TESTOSTERONE LEVEL

KOHN. THE AGING MALE 2006;9:183-188

TESTOSTERONE INJ.(T) vs T PLUS FINASTERIDE vs PLACEBO

x 36 MONTHS IN HYPOGONANDAL MEN PAGE (TENOVER) JCEM 2005;90:1502-1510

EFFICACY AND SAFETY OF TRT IN OLDER MEN WITH LIMITED MOBILITY

N=209 ENROLLED (INCLUDED IN SAFETY ANALYSIS) N=176 (INCLUDED IN EFFICACY ANALYSIS) MEAN AGE = 74

MEAN T = 8.4 nmol/L (3.5-12.1) T GEL DOSE = 5 - 15 gm./day X 6 MO DESIRED T LEVEL = 17.4 - 34.7

LIMITED MOBILITY 1. DIFFICULTY WALKING 2 LEVEL BLOCKS, OR 2. DIFFICULTY CLIMBING 10 STEPS, AND, 3. SCORE OF 4-9 ON THE SHORT PHYSICAL PERFORMANCE BATTERY-

SCALE

OUTCOME – CHANGE IN LEG-PRESS MUSCLE STRENGTH

BASARIA. NEJM, 2010;363:109-122

EFFICACY AND SAFETY OF TRT IN OLDER MEN WITH LIMITED MOBILITY

TESTOSTERONE GEL PLACEBO

N=106 N=103

CARDIOVASCULAR EVENT N=23 N=5

EFFICACY

LEG PRESSURE STRENGTH (NEWTONS) 156.9 27.1 p=0.004

CHEST PRESSURE (NEWTONS) 34.7 0.28 p=0.002

STAIR CLIMBING POWER WITH LOAD 39.2 9.0 p=0.05

BASARIA. NEJM 2010;363:109-122

EFFFICACY AND SAFETY OF TRT IN OLDER MEN WITH LIMITED MOBILITY

BASELINE CHARACTERISTICS RELATED TO CVS RISK

TRT PLACEBO

HYPERTENSION 85% 78% p=0.21

HYPERTENSION Rx 85% 73% p=0.04

HYPERLIPIDEMIA 63% 50% p=0.05

STATIN THERAPY 62% 47% p=0.03

BASARIA. NEJM 2010;363:109-122

EFFICACY AND SAFETY OF TRT IN OLDER MEN WITH LIMITED MOBILITY

CARDIOVASCULAR EVENTS:1. CHEST PAIN 2. SYNCOPE3. MI4. ANGIOPLASTY5. EDEMA6. PVBs7. LV STRAIN PATTERN / EXERCISE8. ST DEPRESSION / EXERCISE9. INCREASED BP10. ATRIAL FIB + CHF EXACERBATION11. STROKE12. TACHYCARDIA WITH FATIGUE13. DEATH14. CAROTID BRUIT AND PLAQUE

BASARIA. NEJM 2010;363:109-122

LIMITED MOBILITY IN GERIATRICS

LIMITED MOBILITY IS A PREDICTOR OF:

1. DISABILITY

2. POOR QUALITY OF LIFE

3. DEATH

BASARIA. NEJM 2010;363:109-122

FRAILTY IN MEN OVER 65 IS ASSOCIATED WITH DECREASED LEVELS OF BIO-AVAILABLE TESTOSTERONE

(n=1469)

FIVE DOMAINS OF FRAILTY:

1.Weakness (grip strength)

2.Shrinking/sarcopenia (↓wt.)

3.Slowness (walking speed)

4.Low activity level (self report)

5.Exhaustion (self report)

CAWTHORN, JCEM, ON-LINE PREPRINT, OCTOBER 2009; 94(10)

HIGHER T LEVELS Ξ LESS LOSS OF LEAN BODY MASS IN OLDER MEN

AGING MEN LOSE MORE MUSCLE MASS AND STRENGTH COMPARED TO AGING WOMEN

--b/o TESTOSTERONE ?

TRT IN OLDER MEN RESULTS IN:

- LEAN BODY MASS

- FAT MASS

- MUSCLE STRENGTH

LeBlanc. JCEM 2011;96:3855-3863

TESTOSTERONE THERAPY IN HYPOGONADAL MEN WITH TYPE-2

DIABETES

IMPROVED:

- FASTING BLOOD SUGAR

- FASTING INSULIN LEVEL

- HbA1c

- WEIGHT

KAPOOR, EUR J ENDOCRINOL. 2006;154:899-906

ANDROGEN DEPRIVATION THERAPY IN pCA: EFFECT ON BLOOD SUGAR

SHAHANI. JCEM 2008;93:2042-2049

EFFECTS OF ANDROGEN DEPRIVATION THERAPY IN pCA ON INSULIN

SECRETION

SHAHANI. JCEM 2008;93:2042-2049

LOW SERUM TESTOSTERONE AND MORTALITY IN MALE VETERANS

Shores. Arch Intern Med. 2006;166:1660-1665

Copyright restrictions may apply.

Shores, M. M. et al. Arch Gen Psychiatry 2004;61:162-167.

Two-year incidence of depression in hypogonadal men, using different total testosterone threshold levels to define hypogonadism

DEPRESSION SCORES INCREASE WITH AGE IN ELDERLY MEN

3

4

5

6

50–59 60–69 70–79 80–89

Age group (years)

Bec

k's

Dep

ress

ion

In

ven

tory

sc

ore

Barrett-Connor et al. J Clin Endocrinol Metab 1999;84:573–77

p < 0.001 for trend

Testosterone Gel Supplementation

for Men With Refractory

Depression: A Randomized,

Placebo-Controlled Trial

                                    

Pope et al., Am J Psychiatry 2003; 160:105-111

N=23

43% testosterone <350 ng/dl

INTRACORONARY TESTOSTERONE INCREASES CORONARY ARTERY DIAMETER IN AGING MEN WITH

CORONARY ARTERY DISEASE

4.3

1.4

3.2

2.8

0

1

2

3

4

5

0.1 1 10 100

Intracoronary testosterone infusion for 2 minutes (nmol/l)

Perc

en

tag

e i

ncre

ase o

f co

ron

ary

art

ery

dia

mete

r

Adapted from Webb et al. Circulation 1999;100:1690–1696.

*p < 0.05; **p < 0.01 versus baseline

*

*

**

ACUTE ANTI-ISCHEMIC EFFECT OF TESTOSTERONE IN MEN WITH

CORONARY ARTERY DISEASE Time to 1mm ST depression Total Exercise Time

Rosano GMC et al. Circulation. 1999;99:1666-1670

TESTOSTERONE IN HEART FAILURE AND CORONARY ARTERY DISEASE

Heart failure – significant morbidity; mortality up to 30% at 1 year

Low T: 1. independent risk factor for worse outcome in HF

2. predictor of peak oxygen consumption

3. risk factor for exercise capacity

4. survival in coronary artery disease

I.V. Testosterone: 1. acutely increases cardiac output

2. decreases peripheral vascular resistance

Testosterone therapy: 1. coronary vasodilation

2. increased coronary blood flow

3. improved angina threshold in CAD

Toma. Circ Heart fail. 2012;5:315-321

TESTOSTERONE SUPPLEMENTATION IN HEART FAILURE:A META-ANALYSIS

Forest plot of exercise capacity in all studies, normalized using SD. This forest plotshows that testosterone therapy resulted in a net pooled improvement in exercise

capacity of 0.52 SD (95% CI, 0.10–0.94 SD).

Toma M et al. Circ Heart Fail 2012;5:315-321

Copyright © American Heart Association

TESTOSTERONE THERAPY IN MODERATE TO SEVERE HEART FAILURE: A META-ANALYSIS

Trials – N=4 Subjects – N = 166 men Treatment period – 12 to 52 weeks Placebo-controlled

Results:1. No difference in cardiovascular events (death, MI, HF, hospitalization)

2. No safety concerns

3. No significant change in PSA

4. Improved: - exercise capacity - NY Heart Association functional class - FBS, fasting insulin, insulin resistance

Conclusion: “Testosterone is a promising therapy to improve exercise capacity in patients with heart failure”.

Toma. Circ Heart Fail. 2012:5:315-321

LONG-TERM EFFECT OF TRT ON BMD IN 72 HYPOGONADAL MEN

BEHRE JCEM 1997;82:2386-2390 (Rx = T injection or patch)

HYPOGONADISM IN PATIENTS TREATED WITH INTRATHECAL MORPHINE

FINCH. CLIN J PAIN. 2000;16:251-254

METHADONE HAS DIRECT INHIBITORY EFFECT ON CULTURED LEYDIG CELL

PRODUCTION OF T

(solid bars-no methadone)

PUROHIT. J ENDOCR. 1978;78:299-300

SUPPRESSION OF TESTOSTERONE AND SEXUAL FUNCTION BY METHADONE AND BUPRENORPHINE

BLIESENER. J CLIN ENDOCRINOL METAB. 2005;90:203-206

EFFECT OF METHADONE VS. BUPRENORPHINE ON TESTOSTERONE AND

SEXUAL FUNCTION IN MALE NARCOTIC ADDICTS

BLIESENER. J CLIN ENDOCRINOL METAB 2005;90:203-206

METH.88MGN=37

BUPR.11MGN=17

CONT.N=15

T-nmol/L 9.7* 17.7 17.0

FREE-pmol/L

27.0* 59.5 (31-94)

SHBG-nmol/L

43.5 46.8 (10-73)

INCIDENCE OF PROSTATE PATHOLOGYAND SERUM TESTOSTERONE LEVELS

0

200

400

600

800

1000

1200

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

>85

age (years)

Tes

tost

eron

e (n

g/d

l)In

cid

ence

(p

er 1

0000

0)

TESTOSTERONE

BPHFAMILIAL PROSTATE CANCER SPORADIC

CANCER

MEDIAN AGE DIAGNOSIS

T serum levels and CaP: a meta-analysis

Outcome of study

No. of studies

No. of subjects Patients Controls

T > in patients 4 343 503

T = in both 15 758 2004

T < in patients 6 380 260

Total 25 1481 2767

Slater S & Oliver RTD. Drugs and Aging 17:431, 2000

INTRAPROSTATIC VS. SERUM LEVELS OF TESTOSTERONE AND DHT

The intraprostatic hormonal environment bears little resemblance to serum levels. “Despite marked increases in serum levels,

prostate levels of T and DHT were unchanged after 6 months of treatment (in hypogonadal men). Gene expression was not altered, cell proliferation was not accelerated and histologic cancers were not increased.”

Marks LS et al, J. Urol (Supp) 2006;175:224.

Destroying the Myth About Testosterone Replacement and Prostate Cancer

Abraham Morgentaler, MD, FACS Low blood levels of testosterone do not protect against

prostate cancer and, indeed, may increase the risk.

High blood levels of testosterone do not increase the risk of prostate cancer.

Treatment with testosterone does not increase the risk of prostate cancer, even among men who are already at high risk for it.

Life Extension Magazine -- December 2008

ABSORPTION RATE OF DIFFERENT TESTOSTERONE PREPARATIONS

Dose Absorption rate

Unit Deliver (mg/day)

TU 80 mg bid 7 % 40mg (25 mg T) 7

GEL 5 g/ 24 hr 10% 5 g (50mg T) 5

PATCH 24.2 mg/ 24 hr 20% 24.2 mg 5

INJECTION 200 mg / 21 days

variable 200 mg 9.5 (average over 21 days)

TESTOSTERONE AND ESTRADIOL BOTH PLAY A ROLE IN TESTOSTERONE-RELATED FUNCTIONS

Testosterone mainly regulates:

- lean body mass

- muscle size

- muscle strength

Estradiol deficiency largely induces fat accumulation

Testosterone and estradiol both play a role in sexual function

Finkelstein. NEJM 2013;369:1011-1022

BENEFITS OF TRT: HYPOGONADAL MEN

Wang C et al. J Clin Endocrinol Metab 2004;89:2085-2098.

IrritabilityAngerFat mass

Sexual function

Mood

Energy

Lean body mass

Bone mineral density

WHEN TO MEASURE TESTOSTERONE

1. SYMPTOMS - strength,energy,motivation - fatigue,lethargy - libido, ED - mood and cognition changes2. Unexplained anemia3. Osteopenia/osteoporosis4. Muscle mass 5. (Chronic opioid use)

Practice Committee(ASRM):Treatment of Androgen Deficiency in the Aging Male.Fert Steril 2004;81:1437-1440

MONITORING

NO PCa OR BREAST CA BEWARE VERY SEVERE OBSTRUCTIVE BPH BEWARE SLEEP APNEA BEWARE POLYCYTHEMIA

FOLLOW:

1.CLINICAL RESPONSE TO TRT

2.PSA – suspicious if change > 1 mcg/L

3.DRE

4.Hb / Hct

SEXUAL INTEREST IN WOMEN IS MORE THAN SATISFACTION OF SEXUAL DESIRE

emotionally close---bonding to partner feeling of being loved / wanted feeling of being attractive sharing sexual feeling for the sake of sharing showing affection, caring, attraction showing partner is missed to herald the end of an argument

Basson, Can J CME;2001,Dec :131-137

SYMPTOMS OF DECREASED TESTOSTERONE IN AGING WOMEN

Sexual Dysfunction

Well-being

Energy

Bone Mass

Sands, Studd Am.J.Med, 1995; 98: 765-795

Frock, Money Psychother Psychosom 1992; 57: 29-33

SYMPTOMS OF ANDROGEN DEFICIENCY IN WOMEN

sexual desire sensitivity to

sexual stimulus

arousability capacity for

orgasm energy

Rako, Psychopharmacol Bull 1997;33:761-766

loss of muscle tone

fatigue thinning pubic hair dry skin motivation sense of well-

being

Davis,Med J Aust 1999;170:545-549

SUBCUTANEOUS TESTOSTERONE IMPLANTS IN WOMEN ON ESTROGEN

SEXUAL ACTIVITY SATISFACTION PLEASURE ORGASM RELEVANCY

CHOLESTEROL LDL HDL- no change

Davis et al Maturitus 1995;21:227-236

ANDROGEN THERAPY IN POST-MENOPAUSAL WOMEN ON

ESTROGENS

RELIEF OF: -depression

-nervous tension

-palpitations

-headaches

-insomnia

Olatunbosun J Soc Obstet Gynaecol Can 1998;20:837-843

Sherwin J Affect Disorder 1988;14:177-187

LONG- TERM TESTOSTERONE TREATMENT IN THE MENOPAUSE

Does not adversely affect improvement in lipoprotein lipids induced by estrogen therapy

Davis, Maturitas, 1995; 21:227

PROFILE OF THE WOMAN MOST LIKELY TO RESPOND TO

ANDROGEN1. Persistent inexplicable fatigue

2. motivation

3. libido

4. well-being

4. Estrogen replete

5. Low bio-available testosterone

Davis JCEM, 1999; 84: 1886-1891

TESTOSTERONE TREATMENT IN POSTMENOPAUSAL WOMEN

The effects of hormonal implants on BMD (grams per cm2), lumbar spine (L1–L4), and femoral trochanter (troc).

Davis S JCEM 1999;84:1886-1891©1999 by Endocrine Society

TESTOSTERONE TREATMENT IN POSTMENOPAUSAL WOMEN

Summary graph showing the grand mean (i.e. means of 6, 12, 18, and 24 months) for each sexuality parameter adjusted for baseline as a covariate. ○, Estradiol implants alone;

▪, estradiol plus testosterone implants.

Davis S JCEM 1999;84:1886-1891

©1999 by Endocrine Society

TESTOSTERONE TREATMENT IN WOMEN

OFF LABEL USE IN CANADA

USE LOWEST EFFECTIVE DOSE

EVIDENCE FOR EFFICACY ONLY IN POST-MENOPAUSAL WOMEN

REPRODUCTIVE AGE WOMEN MAY BE BENEFIT FROM TESTOSTERONE THERAPY AFTER OOPHORECTOMY

SIDE- EFFECTS UNCOMMON AT LOW DOSES

CONTRAINDICATED WITH BREAST OR UTERINE CANCER

THE MANY FACES OF TESTOSTERONE

CLASSICAL HYPOGONADISM

ANDROPAUSE IN WOMEN BONES MUSCLES LIBIDO ERECTILE FUNCTION COGNITION MOOD

ANEMIA CORONARY ARTERY

DISEASE OBESITY DIABETES MELLITUS METABOLIC SYNDROME HIV APATHY OF PARKINSONISM AUTOIMMUNE DISEASE NARCOTIC DEPENDENCE