Consequences of the Use of Anabolic-Androgenic Steroids on Female Athletes’ Fertility


Research

Steroid

Dose

Effect

Obasanjo et al. [28]

Nandrolone decanoate

25 mg/3 weeks for 24 months

Increase in uterine weight

Increased endometrial thickness

Increased glandular area

Altered glandular architecture

Rubiera-Gerez et al. [30]

Nandrolone decanoate

One, two, and three doses of 3 mg/kg BW in the 1st, 2nd, and 3rd weeks

Estral acyclicity

Destruction of follicular units

Absence of corpus luteum

Morphological changes in uterus

Mobini-Far et al. [48]

Nandrolone decanoate

15 mg/kg once daily during 2 weeks

Endometrial atrophy

Glands with tortuous and irregular branching

Lack of normal infiltration of eosinophilic leukocytes into the endometrium

Cherici-Camargo et al. [31, 32]

Nandrolone decanoate

6 mg/kg BW for 4 weeks and exercise

Changes in weight of ovaries and hypophysis, number of antral and atretic follicles, and the area of corpus luteum

Estral acyclicity

De Almeida-Chuffa et al. [33]

Nandrolone decanoate

5 mg/kg BW for 4 weeks and exercise

Histomorphometric changes to the uterus

Estrus acyclicity

Decreased thickness of the epithelium and endometrial stroma

Karbalay-Doust and Noorafsham [49]

Nandrolone decanoate

One, two, and three doses of 3 mg/kg BW in the 1st, 2nd, and 3rd weeks

Decrease in the volume of the ovary, cortex, and medulla

Reduction of oocytes

Bordbar et al. [35]

Nandrolone decanoate

3–19 mg/kg for 1 month

Changes in dimension of the ovaries, number of follicles, and sex hormone levels


BW body weight



Other studies have compared the effects of using ND and other AAS. In this line of work, Blasberg et al. [39] observed that the treatment with 17 α-methyltestosterone, methandrostenolone, and ND, at doses that mimic those used by human athletes , produced reversible and a dose-dependent sexual receptivity conduct and estrous vaginal cytology in rats over a 2-week period. During the intervening period, the effects of the treatment with ND at a dose of 7.5 mg/kg on the estrous cycle of these animals were longer while vaginal estrous resumed within 2 months of treatment completion. Another study [32] analyzed the effects of using ND (7.5 mg/kg of body weight), testosterone esters (7.5 mg/kg of body weight), or both steroids at once during 8 weeks. The results showed that the steroidal treatment did not affect the uterine weight. In this study, all the androgenized females presented estral acyclicity and endometrium characterized by papilliferous luminal lining, edematous stroma with hemorrhagic areas, and secretory activity. Changes were observed in the morphometrical thickness parameters of the luminal epithelium, myometrium, and perimetrium in the androgenized groups. In addition, none of the female rats got pregnant when treated with steroids in the pre-gestational period. Thus, the treatment during organogenesis affected negatively the reproductive parameters. Collectively, these findings are summarized in Table 14.1.

Some other AAS have also been used in the investigation of the effects caused by these substances on the female reproductive system, such as testosterone undecanoate [50] or testosterone [51] (summarized in Table 14.2). Bento-Silva et al. [50] observed that testosterone undecanoate (5 mg/kg, 3 days/week for 4 weeks) combined with moderate physical training (50 min/day swim, 5 days/week for 4 weeks) altered the reproductive system of rats through interruption of the estrous cycle and ovarian atrophy. Triemstra and Wood [51] observed inhibitory effects on female reproduction by administering testosterone (1.0 µg/µl) to female hamsters (n = 12). Bronson et al. [37] investigated (9 weeks) adult female mice exposed to a combination of four AAS (testosterone, testosterone cypionate, methyltestosterone, and norethandrolone) at doses that were either one or five times the androgenic maintenance level (silastic capsule implanted under the skin on the back of a mouse). These authors suggest that chronic treatment with AAS resulted in suppression of LH, follicle-stimulating hormone (FSH), and estradiol and cessation of the vaginal cycle.


Table 14.2
Effect of using different anabolic-androgenic steroids in the female reproductive system and reproductive performance in animals







































Research

Steroid

Dose

Effect

Bronson et al. [37]

Testosterone, testosterone cypionate, Methyltestosterone

Norethandrolone

Implanted silastic capsule under the skin on the back of a mouse

Suppression of LH, FSH, and estradiol

Cessation of vaginal cycle

Blasberg et al. [39]

17 α-methyltestosterone, methandrostenolone

Nandrolone decanoate

7.5 mg/kg BW

5.6 mg/kg BW

Disrupts female neuroendocrine function

Cherici-Camargo et al. [31, 32]

Nandrolone decanoate

Testosterone esters

7.5 mg/kg BW

7.5 mg/kg BW

Estral acyclicity

Papilliferous luminal lining

Edematous stroma

Changes in morphometrical thickness parameters of luminal epithelium, myometrium, and perimetrium

Bento-Silva et al. [52]

Testosterone undecanoate and exercise

5 mg/kg BW

3 days/week

4 weeks

Interruption of estrous cycle

Ovarian atrophy

Triemstra and Wood [51]

Testosterone

1.0 µg/µl

Inhibited female reproduction


BW body weight, LH luteinizing hormone, FSH follicle-stimulating hormone



Research in Humans


Strauss et al. [7] examined the effects of high use of AAS in ten weight-trained women athletes in a pioneer study in the field of sports research and observed modifications in several body features: voice changes (ten cases); increased facial hair (nine cases); clitoral enlargement (eight cases); aggressiveness (eight cases); menstrual abnormalities (seven cases); increased libido (six cases); acne (six cases); decrease in breast size (five cases); body weight gain (five cases), and hair loss (two cases). Almost all these athletes were specialized in strength modalities but none of them practiced the most affected activities for the use of anabolic substances, such as bodybuilding, powerlifting, or weightlifting.

Considering the frequent use of AAS and their potential health risks, several studies were performed assessing the effect of these drugs in females. Studies propose the use of AAS relationship with suppression of gonadal steroidogenesis [53], menstrual irregularity [53, 54], and uterine atrophy [18]. Clark et al. [55] suggested that the existence of different routes of the steroid metabolism and its relationship with the reproductive function may be the cause of the decrease in time of vaginal estrus during 2 weeks of treatment with AAS. Also, the absence of estrus (i.e., persistent diestrus) during the recovery period, pronounced with testosterone use, may be related to the existence of different routes of metabolism of the steroid and its relationship to the reproductive function .

Malarkey et al. [56] compared nine female weightlifters using steroids with seven non-user weightlifters. Thirty-fold elevations of serum testosterone were detected in the women that used AAS. The authors observed that serum testosterone levels exceeded the upper limits for normal male testosterone concentrations in three of these women. Moreover, significant compensatory decrease in sex-hormone-binding globulin and decreased thyroid-binding proteins were noted in these athletes. High-density lipoprotein cholesterol decreased by 39 % in the female weightlifters using AAS.


Example of Abuse of Anabolic-Androgenic Steroids in Sport: The Case of the German Democratic Republic


The German government awards the prestigious Heidi-Krieger-Medaille to individuals who have a significant career in the fight against one of the main scourges in modern sport: doping. This award is named in the honor of Andreas Krieger (ex-athlete from the German Democratic Republic (GDR), born as Heidi Krieger) .

The case of Heidi (Andreas) Krieger, European shot put champion in 1986, who retired in 1990, is perhaps one of the most dramatic documented cases regarding the use and abuse of AAS. During the trial against Ewal and Höeppner, Krieger reported the psychological and physiological effects of the massive use of steroids during youth that made her look like a man, and drove her to serious psychological disorders and attempted suicide. Krieger underwent sex reassignment surgery and changed her name to Andreas Krieger. Nowadays, he lives in Germany, married to former East German swimmer Ute Krause, who was also a victim of massive doping.

Heidi Krieger was born in East Berlin (GDR) in July 1966. At the age of 14, she was recruited for her athletic talent to be part of the Dynamo Berlin elite sports club . Two years later, she entered into a massive doping project organized by the communist GDR government. To start the program, numerous scientists from the GDR developed a highly sophisticated and methodological plan, backed by the government itself and under the control of the Ministerium für Staatssicherheit (STASI) [57]. The program managers and key players were Manfred Ewald (minister of sports, 1961–1988, and president of the National Olympic Committee, 1973–1990) and the doctor Manfred Höeppner. They did not act alone, and certainly several official institutions and many researchers were involved, among them Rüdiger Häcker, director of the Institute of Leipzig and responsible for a program to improve the effectiveness of steroids and avoid its detection. Also, different researchers from Jenapharm pharmaceutical laboratories participated.

The secret doping program developed in the GDR was successful in the field of sports and allowed the country to reach leading positions in many international sporting areas, such as swimming, athletics, rowing, canoeing, and weightlifting. However, there were many side effects, especially regarding the athletes’ physiological and psychological well-being, with an average of 30 annual victims as a consequence of the biological manipulation of their athletes.

To implement the project, various work programs were created, including the development of steroids and their use. Their massive use started from the early 1970s and was formalized as state plan 14.25 in 1974 [5759]. To optimize the systematic doping, the aim of one of the projects was to develop different steroids for their athletes. The main steroid used was a variant of Dianabol (17α-methyl-17β hydroxy-1.4-androstandiene-3-one) which they named Oral-Turinabol (4-chlor-1-dehydro-17α-methyltestosterone). However, they used and performed researches with other oral anabolic substances (17α-methyl-17β-hydroxy-5α-androstane-3-on; 11-β-hydroxy-OT; 4-chlor-17α-methyl-17β-hydroxy-5α-androst-4-en-3-one; 4-chlor-17α-methyl-17β-hydroxy-5α-androst-4-en-3-one; 17α-methyl-17β hydroxy-1.4-androstandiene-3-one), Testosteron-Ampullen injectables, Testosteron-Depot-Ampullen, Testo-Tropin-Ampullen, Turinabol-Ampullen (phenylpropionate ester of 17β hydroxy-19-norandrost-4-en-3-one) or Turinabol-Depot-Ampullen (decanoate ester of phenylpropionate ester of 17β hydroxy-19-norandrost-4-en-3-one), nasal spray (testosterone esters and androstenedione), and stimulating testosterone synthesizing substances (Gonabion-Ampullen and Clomiphen).

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Jun 8, 2017 | Posted by in GYNECOLOGY | Comments Off on Consequences of the Use of Anabolic-Androgenic Steroids on Female Athletes’ Fertility

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