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2 Naturally Occurring Steroid Hormones

2 Naturally Occurring Steroid Hormones

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16.2



Naturally Occurring Steroid Hormones



209



Oral contraceptives, i.e.; birth control pills, contain progesterone (a progestin) in combination with various estrogens.

These hormones mimic the effects of pregnancy, which prevent the release of eggs from the ovaries.

Mineralocorticoids and glucocorticoids are synthesized in the adrenal cortex from progesterone. Mineralocorticoids primarily regulate reabsorption and excretion of sodium (a mineral), potassium (a mineral), and water by the kidneys.

Glucocorticoids regulate carbohydrate, protein, and lipid metabolism, as well as inflammatory reactions and “stress-coping”

mechanisms.



O



O



CH3



CH3



CH2OH



O



O



O

CH3



OH



O



O



CH2OH

OH



O



17α-Hydroxyprogesterone



CH3



HO



CH2OH

OH



11



CH3



O



Aldosterone

(A Mineralocorticoid)



Corticosterone



11



CH3



CH3



O

11-Deoxycorticosterone



CH3



HO



CH3



O

Progesterone

(A Progestin)



CH2OH



11



CH3



O



O

O



CH3



HO



11



CH3



CH2OH



CH3



O

11-Deoxycortisol



Cortisol

(A Glucocorticoid)



Structure 16.4



Androgen is a general term used to describe steroid hormones that control or regulate the development and maintenance of

male characteristics. It is most often associated with testosterone and its natural or synthetic derivatives. They usually have a basic

skeleton containing 19 carbons and are common precursors in the production of estrogen. Most are surprised by the fact that

estrogen does not have a specific structure. It is routinely (and rather loosely) used to define a group of hormones that produce

female characteristics including estradiol, estrone, and estriol, or any combination of the three.

Androgens are the only class of controlled or regulated steroids and are thus the only steroids of forensic interest.



210



16



Anabolic Steroids



O

CH3



CH3



OH



O



CH3



CH3



CH3



OH



CH3



O



O

Dehydroisoandrosterone



17α-Hydroxypregnenolone



CH3



CH3



HO



HO



O



Testosterone

(An Androgen)



Androsterone



CH3



O



CH3



OH



HO



HO

Estrone



Estradiol



CH3



OH



OH



HO

Estriol



Structure 16.5



16.3



Anabolic Steroids



16.3.1 General Structure

Although the term “steroid” defines a large number of biological molecules in the lipid class, its use in popular culture references

“anabolic steroids” almost exclusively. Anabolic steroids are synthetic derivatives of testosterone, a naturally occurring hormone

in the body that regulates various functions including skeletal muscle growth (anabolic effects) and the development of male

sexual characteristics (androgenic effects).

CH3



H3C

CH3



CH3



CH3



O



HO

Cholesterol



Structure 16.6



CH3



CH3



Testosterone



OH



16.3



Anabolic Steroids



211



Anabolic steroids were originally developed in the late 1930s to treat hypogonadism, a condition in which the testes do not

produce enough testosterone for normal growth, development, and sexual functioning. They were later commonly used to treat

delayed puberty and specific types of impotence.



16.3.2 Physical and Psychological Effects

A particularly important effect of anabolic steroid use is the stimulation of protein synthesis, which results in (among other

things) the growth of skeletal muscle and bone tissue. This increase in muscle mass and bone density enhances physical

performance and endurance, a clear advantage in competitive sports. Steroid abuse by professional athletes has become so

widespread that it often affects the outcome of sporting competitions. Currently, most steroids are banned in every major

amateur and professional sport. In an effort to maintain the integrity of sporting competitions, sanctioning bodies require

periodic testing for “doping” and impose serious penalties on those not in compliance.

Steroid use has damaging side effects, including elevated blood pressure, severe acne, liver damage (where it is metabolized),

harmful changes in the composition of cholesterol (LDL to HDL ratios, low- and high-density lipoproteins), and alterations in

heart structure (abnormal thickening of left ventricle) resulting in arrhythmia, congestive heart failure, and heart attack. There are

also male- and female-specific side effects. In females, abnormal hair growth, deepening of the voice, enlarged clitoris, and

decreased or absent menstrual cycles can occur. In males, testicular atrophy, development of breast tissue, enlarged Adam’s apple,

and temporary infertility may result.

Psychological effects are primarily related to mood disturbances or disorders that result in depression and overly aggressive or violent behavior. Chronic users may also develop symptoms of dependency and withdrawal.



16.3.3 Methods of Administration

Anabolic steroids are available in capsules, tablets, gel, patches, and injections. The level of effectiveness is directly related

to the rate of absorption. Although oral administration is the most convenient method, injection is the most effective. Steroids

taken by mouth are rapidly converted into inactive metabolites resulting in limited absorption. Dermal patches exhibit slow

or limited absorption because active steroids must first permeate the skin prior to absorption. Injection is the preferred method

of administration because steroids are directly introduced into deep muscle tissue.



16.3.4 Nomenclature of Anabolic Steroids

The nomenclature of androgen-based steroids follows the same general procedures as those developed for the naming of organic

compounds (Chap. 4). Saturated hydrocarbons are members of the alkane class and contain only carbon–carbon single bonds.

Unsaturated hydrocarbons are members of the alkene class and contain at least one carbon–carbon double bond.

The names for anabolic steroids can be divided into three basic parts. The first part, “androst,” indicates the presence of

the basic skeletal structure of an androgen, usually testosterone. The second part describes saturation or degree of unsaturation on the androgen skeleton. In these cases, androst precedes the suffix “ane” for saturated androgens (androstane) and the

suffix “ene” for unsaturated forms (androstene). Some steroids contain more than one carbon–carbon double bond. In these

cases, the suffix “ene” is amended to “adiene” or “atriene” depending on the number of double bonds present. For example,

androstadiene defines an androgen molecule with two points of unsaturation (two carbon–carbon double bonds). Points of

unsaturation usually occur in the rings of sterane and are rarely found in substituted groups attached to the characteristic

four-fused ring system. They are located using the first carbon in the double bond.

CH3

12

11



1

2

3



A

4



C



9

10

5



B



14



11



D 16



CH3



15



1



8



2



7



3



6



Sterane



Structure 16.7



13



12



17



A

4



C



13

14



9

10

5



B



CH3

12



17



D 16

15



1



8



2



7



3



6



An Androstene

(4-Androstene)



11



CH3

A

4



C



13

14



9

10

5



B



8

7



6



An Androstadiene

(1,4-Androstadiene)



17



D 16

15



212



16



Anabolic Steroids



The last part of the name describes characteristic functional groups attached to sterane. Androgens containing ketone functional groups end in “one,” while those containing hydroxyl groups (−OH, alcohols) end in “ol.” Ketone groups are typically

found at carbon 3 and hydroxyl groups are commonly substituted at carbon 17. The rigid structure of the four-fused ring system

is planar, allowing only substitutions above or below the plane. The positional substitutions above the plane are defined as beta

(b) substitutions and those below the plane are alpha (a). Androstane containing a ketone at carbon 3 would be correctly named

3-androstanone, which is commonly shortened to simply androstanone. The name of androstene containing the same substitution would correctly locate both the double bond and the ketone group, for example, 4-androsten-3-one, usually shortened to

just androstenone. A hydroxyl group substituted at carbon 17 of androstenone, above the plane of the ring (b position), would

change the name to 4-androsten-17b-ol-3-one.

CH3



CH3

C



CH3



D



3



A



C



CH3



1



17



D



B



3



O

An Androstanone

(3-Androstanone)



A



C



CH3



1



O



OH



CH3



17



17



D



1

5



B



4



An Androstenone

(4-Androsten-3-one)



3



O



A



5



B



4



4-Androsten-17β-ol-3-one



Structure 16.8



Careful examination of the name would be interpreted as a carbon–carbon double bond from carbon 4 to carbon 5 (4-androsten), an OH up at carbon 17 (17b-ol-), and a ketone functional group at carbon 3 (3-one). This systematic method is used to

explicitly define the structure of steroids. Unfortunately, most natural and synthetic anabolic steroids are commonly referenced

using generic names.



16.3.5 Frequently Encountered Steroids

The possession or sale of anabolic steroids without a valid prescription is illegal. Androgenic (promoting masculine characteristics) anabolic (tissue-building) steroids are Schedule III controlled substances defined as “any drug or hormonal substance

chemically and pharmacologically related to testosterone (except estrogen, progestins, and corticosteroids) that promotes muscle growth.” Street names include arnolds, gym candy, pumpers, roids, and juice. Some of the most commonly abused anabolic

steroids are listed below.



16.4



Analytical Methods



213

CH3

CH3



O

CH3



H

H



OH



CH3



H



CH3



H

H



O



H

H



H



H



O



HO



Equipoise (Boldenone)

(1,4-Androstadien-17β-ol-3-one)

C19H25O2 M.W. 285 g/mol



Androstenediol

(5-Androsten-3β,17β-diol)

C19H30O2 M.W. 290.44 g/mol



Androstadienedione

(1,4-Androstadien-3,17-dione)

C19H24O2 M.W. 284 g/mol



OH



CH3



O

CH3



OH



OH



CH3



CH3



O



(CH2)8CH3



CH3

CH3



H



H



H



H



H



O



H



H



H



H



O



H



O

Nandrolone

(19-Nortestosterone)

(17β-Hydroxyestra-4-en-3-one)

C18H26O2 M.W. 274.40 g/mol



Methandrostenolone

(17α-methyl-17β-hydroxy1,4-androstadien-3-one)

C20H28O2 M.W. 300.44 g/mol



H



Nandrolone Decanoate

(Deca-Durabolin)

(19-Nortestosterone17β-decanoate)

C28H44O3 M.W. 428.65 g/mol



O

OH



CH3

CH3



CH3

CH3



H

H



H



H



CH3

H



Testosterone

(17β-Hydroxyandrost-4-en-3-one)

C19H28O2 M.W. 288.43 g/mol



O



H

H



H



O

Testosterone Caproate

(17β-Decanoatetestosterone)

C29H46O3 M.W. 442.68 g/mol



Testosterone Cypionate

(17β-Cypionatetestosterone)

C27H40O3 M.W. 412.61 g/mol



O



O

CH3



O



CH3



(CH2)8CH3



H



O



O



O



O



CH3



(CH2)5CH3



O



CH3



CH3



OH

CH3



CH3

H



CH3



H



H



H



H



H



HN



H



N



O



O



H



H

Testosterone Enanthate

(17β-Heptanoatetestosterone)

C26H40O3 M.W. 400.6 g/mol



Trenbolone Acetate

C20H24O3 M.W. 312.4 g/mol



Winstrol

(Stanozolol)



Structure 16.9



16.4



Analytical Methods



16.4.1 Visual Inspections

The illicit steroid market is inundated with an unknown number of genuine, chemically modified, mixed, and even

counterfeit steroids, available in forms ranging from injections, capsules, tablets, dermal patches, ointments, and lotions.

It is virtually impossible to gain even the slightest insight on the identity of a steroid using visual inspection. Mexico,

Denmark, Australia, and the Netherlands are a few of the worldwide suppliers of anabolic steroids (Fig. 16.1).



16.4.2 Gas Chromatography Mass Spectrometry

Presumptive color-screening tests for the identification of anabolic steroids do not exist. FTIR analysis is often of little value

due to the size and complexity of steroid molecules. Therefore, GCMS is the preferred technique when examining this group



214



16



Anabolic Steroids



of controlled substances. Methanol is the solvent of choice; a small amount of suspected steroid liquid or solid is dissolved

(or mixed) in methanol and the resulting solution is analyzed.



16.4.3 Mass Spectra of Commonly Encountered Steroids

The mass spectra of several steroids commonly submitted to forensic laboratories for analysis are shown below. Most structures are provided in previous pages for comparison and parent ion peak (M+) identification (Fig. 16.2a–g).



Fig. 16.1 Representative forms of steroids packaged for distribution.



16.4



Analytical Methods



Fig. 16.1 (continued)



215



216



16



a



Anabolic Steroids



Mass Spectra of Commonly Encountered Steroids

122



9500

9000

8500

8000

7500

7000

6500

6000

5500

5000

4500

4000

3500

3000

2500

2000

1500

1000

500

0



Androstadiendione



91

159

35



179199 227 251



50



100



150



200



284



250



503



327 356377 403 430



300



350



400



450



500



91 105

9000

8000

7000

6000

5000

4000

3000

2000

1000

0



145

119



55



131



67



41



161



290



205

179



272

239 257



190

40



700000

650000

600000

550000

500000

450000

400000

350000

300000

250000

200000

150000

100000

50000

0



Androstenediol



79



60



80



100



120



140



160



180



200



228

217

220



240



122



91

41 55

40



66



60



77

80



100



120



280



Boldenone



134147



107



260



140



159 173185 199 211 227 240 253 271 286

160



180



200



220



240



260



280



Fig. 16.2 The MS spectra for steroids commonly submitted to forensic laboratories are shown. Correlate steroid structural formulas shown in

struct. 16.9 to their corresponding spectra and identify M+ peaks. Note: Struct. 16.9 does not provide a structure for all spectra.



16.4



Analytical Methods



217



b

122

9000

8000

7000

6000

5000

4000

3000

2000

1000

0



Methandrostenolone



91

43

55 67

40



9000

8000

7000

6000

5000

4000

3000

2000

1000

0



60



79

80



107



147 161

173185 199 213 227 242

254 267 282 300



100 120 140 160 180 200 220 240 260 280 300

253



43



Methandriol



213



91 105

145

119



79



55



271



159



131

67



173



197

185



228



286



304



240

40



60



80



100 120 140 160 180 200 220 240 260 280 300

123136



43

9000

8000

7000

6000

5000

4000

3000

2000

1000

0



Methenolone Acetate



79

93 107



161

302



65

40



Fig. 16.2 (continued)



134



60



246 269 284

186

199215228



344



316329



80 100 120 140 160 180 200 220 240 260 280 300 320 340



218



16



c

136

9500

9000

8500

8000

7500

7000

6500

6000

5500

5000

4500

4000

3500

3000

2500

2000

1500

1000

500

0



Methenolone Enanthate



43



113

161

79 95

186

284

202 223241 259



60



302



414



372

330346



40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400

274



110

9000



Nandrolone



8000

7000

6000



91



5000



79



4000

3000



41



55



147



67



131



2000



215



160 173

185



1000



231



197



256



242



0



40



60



80



100



120



140



160



180



200



220



240



260



280



110

9500

9000

8500

8000

7500

7000

6500

6000

5500

5000

4500

4000

3500

3000

2500

2000

1500

1000

500

0



274



156



43



Nandrolone Decanoate



256

71

91

428



231

135

173 199



316



343



40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420

Fig. 16.2 (continued)



Anabolic Steroids



16.4



Analytical Methods



219



d

110

9500

9000

8500

8000

7500

7000

6500

6000

5500

5000

4500

4000

3500

3000

2500

2000

1500

1000

500

0



43

274

147



Nandrolone Laurate



183



456



256

91



71



231



129



213



165



327 355



40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400420440

302

9000



Norethandrolone



8000

7000



231

85



6000



110



57



5000



215



4000

3000



43

161

123135

147

175



2000



72



1000



97



255

187

199



285



243



0



40



60



80



100



120



140



160



180



200



220



273



240



260



280



300



231

9000



Stanolone



8000



290



55



7000

6000

5000



41



67 81



4000



95 107 123



3000



163

135 149



2000

1000



199

215

175 187



246257 272



0



40

Fig. 16.2 (continued)



60



80



100



120



140



160



180



200



220



240



260



280



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