eMedinewS Editorial

Health Care 341 Comments

MORE ABOUT CASTRATION

Castration medical (chemical) vs surgical

The treatment is used for
1.     Treatment of prostate cancer with metastasis
2.     Punishment to sexual offenders
3.     Voluntary to reduce the excessive sexual desires or coping with a sexless marriage.
4.     Spiritual reasons
5.     Eunuchs ( castrated males)

Castration can be
1.  Surgical: Removal of testicles. In China, castration included removal of the penis as well as the testicles. Both organs were cut off with a knife at the same time. ( Eunuchs). Castration is the term used for removal of the testis and Emasculation or Penectomy for removal of the penis
2.  Chemical: reducing the testosterone levels or blocking its effect in the blood

Castration in Hindi Movie
Zakhmi Aurat is a 1988 Indian Hindi movie starring Dimple Kapadia and Raj Babbar and directed by Avtar Bhogal. It is about women who have been raped and how they get revenge by castrating the rapists. Kapadia played a gang-raped cop who abandons her uniform to avenge her wrongdoers by castrating them.

Modalities available
1.  Orchiectomy (surgical castration)
2.  Gonadotropin releasing hormone (GnRH) agonists or luteinizing hormone (LH) releasing hormone   agonists (medical castration)
3. Gonadotropin releasing hormone (GnRH) antagonists
4. Antiandrogens
5.  Estrogens and progesterones
6. Ketoconazole
7.Combined androgen blockade (CAB), which uses a GnRH agonist along with an antiandrogen (for maximal depletion of testosterone activity).

Commonly used procedures

1.  Synthetic GnRH analog- Leuprolide (lupron) for cancer prostate
2.  Progesterone- Medroxyprogesterone acetate (Depo Provera) for sex offenders
3.  Anti androgen- Cyproterone (Androcur, Cyprostat or Siterone) on both.

Sexual offenders
1.  The drug must reduce sex drive
2.  Should not produce gynaecomastia
3.  Is not debilitating for the man.

Types of sexual offenders

• Paraphiliac (commits sex offenses because they are sexually aroused by the act). Drug of choice: Depo provera
• Others are motivated by violence or other non-sexual factors ( Depo provera not the drug of choice)

Surgical castration ( for ca prostate with metastasis)
1.   Used in ca prostate
2.   Bilateral orchiectomy
3.   Simple and cost-effective procedure.
4.   Following surgery, serum testosterone levels rapidly decrease to castrate levels (<20 ng/mL)
5.   Of choice when immediate decrease in testosterone is necessary (impending spinal cord compression in ca prostate).
6.  Side effects include vasomotor symptoms (hot flushes), weight gain, mood lability, fatigue, gynecomastia, cognitive changes, impotence, loss of libido, osteopenia, and dyslipidemia

Anti androgens (For both Ca prostate and reducing sexual drive)

1. They bind to androgen receptors and competitively inhibit their interaction with testosterone and dihydrotestosterone.
2. Unlike medical castration, anti androgens do not decrease LH levels and androgen production
3. Testosterone levels are normal or increased.
4. Men on its monotherapy do not have the same spectrum of side effects that are due to low levels of  testosterone, and many maintain some degree of potency.
5. Hepatotoxicity, gynecomastia, and breast pain are common side effects with the nonsteroidal antiandrogens .
6.  Antiandrogens are not commonly used as monotherapy.
7. Are generally used in combination with a GnRH agonist, either continuously (combined androgen blockade (CAB)), or for two to four weeks during the initiation of treatment with a GnRH agonist, in order to prevent a disease flare due to the transient increase in testosterone levels.
8. The nonsteroidal antiandrogens available are flutamide ( 250 mg TDs), bicalutamide (tabi 50mg tab, 150 mg once daily), and nilutamide (once daily second generation).
9. Cyproterone acetate- CPA, a steroidal antiandrogen, is as effective as estrogens or flutamide, with better tolerability.

Pure GnRH antagonists

1. Suppress testosterone while avoiding the flare phenomenon of GnRH agonists.
2.  Bind to the GnRH receptors on pituitary gonadotropin-producing cells, but do not cause an initial release of luteinizing hormone or follicle stimulating hormone (FSH).
3.  Abarelix is a chemically modified approved GnRH antagonist.
4.  A second GnRH antagonist, degarelix, was approved by the FDA. It suppresses testosterone levels within three days in 96 percent of patients, an outcome not achieved in patients treated with leuprolide. Suppression of serum testosterone levels is maintained for the duration of the twelve month trial.

Synthetic GnRH analogs

1. Have greater receptor affinity and reduced susceptibility to enzymatic degradation compared to the natural GnRH molecule, and are approximately 100-fold more potent.
2. GnRH (also termed luteinizing hormone releasing hormone (LHRH)) agonists bind to the GnRH receptors on pituitary gonadotropin-producing cells, causing an initial release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH), which causes a subsequent increase in testosterone production from testicular Leydig cells.
3. After about one week of therapy, GnRH receptors are down-regulated on the gonadotropin-producing cells, with a decline in the pituitary production of LH and FSH.
4. The fall in serum LH leads to a decrease in serum testosterone to castrate levels within three to four weeks after the start of treatment . Continued treatment maintains serum testosterone at castrate levels.
5. The decrease in testosterone production is generally reversible upon cessation of GnRH agonist therapy.
6. However, testosterone production does not always return to baseline levels and may be related to the duration of GnRH agonist therapy, patient age, and other factors.
7. The transient rise in LH when GnRH therapy is initiated can cause a surge in serum testosterone, which may stimulate prostate cancer growth.
8. This “flare” may cause an increase in bone pain, bladder obstruction, or other symptoms due to prostate cancer.
9. Thus, initial treatment with GnRH alone is contraindicated in men with severe urinary tract obstruction or painful bone metastases.
10.The flare phenomenon can be effectively prevented with antiandrogen therapy, which blocks the effect of the increased serum testosterone.
11. In practice, antiandrogen therapy is often started seven days prior to GnRH agonist initiation for men at high risk of flare symptoms, or concurrently for asymptomatic patients. Antiandrogen therapy is then continued for two to four weeks.
12.The main effects of GnRH agonists are due to androgen deprivation and are similar to orchiectomy. These include impotence, loss of libido, vasoactive symptoms, fatigue, weight gain, gynecomastia, osteopenia, and dyslipidemia.
13. Available drugs: Daily subcutaneous administration of leuprolide (1 mg/day). This approach had efficacy similar to oral diethylstilbestrol (DES, 3 mg per day), but without the cardiovascular toxicity;  Depot formulations: Leuprolide, goserelin, triptorelin, Buserelin. Dose Leuprolide: (3 monthly 11.75 mg, monthly 3.75mg).

Sexual offenders ( Choices)
Depo-Provera (MPA)
1.  Inhibits the abilities of pedophilias to assault children.
2.  The progesterone counteracts the biological tendencies that lead men to rape children.
3.  By lowering testosterone it reduces sex drive. Males can have sexual intercourse but do not want to.
4.  It also decreases aggressive tendencies by reducing testosterone.
5.  The elimination of testosterone production in a man’s body drastically reduces or eliminates his sex drive.
6.  The goal of treatment is to eliminate the desire of a sex offender who is motivated by sexual arousal to re-offend.

Antiandrogens

1.  Are another method of chemical castration.
2.   Work by blocking certain receptors in the body to which testosterone attaches.
3.  The goal is to block the effects of testosterone on the male body and return levels to that of a pre-pubescent boy.
4.  The sex offender experiences reduced libido, theoretically eliminating the desire of a sex offender to re-offend.

Other methods
Ketoconazole
1.  Is an oral antifungal agent
2.  Inhibits effects on both testicular and adrenal steroidogenesis, through its effects on the cytochrome P450 enzymes.
3.  Its long-term use is limited by gastrointestinal and hepatic side effects, resulting in poor adherence.
4.  Can decrease serum testosterone to castrate levels within 24 hours
5.  Occasionally useful as initial therapy is for patients with spinal cord compression or other acute symptoms due to metastatic prostate cancer who either decline or are not candidates for bilateral orchiectomy.

Estrogen and progesterone

Inhibit the release of LHRH from the hypothalamus, thus suppressing pituitary LH  release and thereby reducing testosterone.
High estrogen levels can lower serum testosterone to castrate levels in one to two weeks.
Estrogens are associated with impotence, loss of libido, and lethargy.
Estrogens may help prevent bone loss, even in low doses (eg, DES 1 mg per day).
Diethylstilbestrol
Increase in the incidence of cardiovascular events, including myocardial infarctions, cerebrovascular accidents, and pulmonary emboli.
A dose of 3 mg per day is required to maintain castrate levels of testosterone, but cardiovascular toxicity remains prohibitive with this dose.
The availability of GnRH agonists, which do not have the excess cardiovascular morbidity seen with DES, led to the decreased use of DES.
Other estrogens and progesterones include conjugated estrogens, ethinyl estradiol, chlorotrianisene and medroxyprogesterone acetate.
A formulation of conjugated estrogens (Premarin) is Premarin (1.25 mg) either once or three times daily.
Transdermal estradiol is associated with castrate levels of testosterone.

Dr KK Aggarwal
Editor in Chief

Death of Osama and the eight years cycle of Chanakya

Uncategorized 336 Comments

The death id Osama reminds me of Chanakya Niti. Chanakya in his neti wrote that the cycle of corruption does not last for more than eight years. He said that people who acquire money by unethical means will have to pay back to the society within eight years. Right or wrong, whether you believe in Chanakya Neti or not it provides a good message for the youngsters in the society to follow the right path of truthfulness. Lord Krishna in Bhagwad Gita has written that everybody has to pay the price of his bad deeds or karmas sooner or later. It is the sum total of bad and good karmas which decides the ultimate fate. Chanakya probably meant that all those who keep on earning money by unethical means and not doing simultaneously good deeds will have to suffer within eight years. Apart from this fact of Chanakya, the eight years cycle is also seen in public bhedchal. Public can not be befooled for more than eight years in a succession. Eight years here is an arbitrary number and may mean six years or ten years. If we see the past one can visualize the public behaviour changing every 6-10 years as far as their preference for a particular type of health wave is concerned. There was time of Sherry Lewis weight management program which came like a storm, stayed in the market for six to eight years and then vanished all together. At that time everyone was crazy for getting their weight management done the Sherry Lewis way. Then came the era of Personal Point which saw a chain of weight management programmes lasting for a few years. This was followed by weight management the Vandana Luthra way. She is persisting in the market as she keeps on diversifying into another fields. Weigh management era was followed by the era of “Reiki”. During this period all the newspapers were full of reiki advertisements and every second person in the family wanted to become a reiki master. The latest craze is for drinking ghiya juice and doing alom-vilom Pranayama By Ramdev. How long will it last the time will tell. He is using all principles of marketing, PR and advertising in this campaign. Craze of yoga in the public was also there in Indira Gandhi’s time when Dhirendra Brahmchari did the same through the TV media. But it was short lasting as he did not apply the principles of advertisement, marketing and PR at that time. In terms of spirituality one also saw a wave of transcendental meditation by Maharishi Mahesh Yogi but the movement did not last long as he quickly realized that selling spirituality in India was not easy and the time for the same was not ripe. In terms of public behaviour one has also seen eras of cycling, exercising, jogging, aerobic dancing, western dancing craze etc.