All about castration

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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

 Synthetic GnRH analog- Leuprolide (lupron) for cancer prostate

  1. Progesterone- Medroxyprogesterone acetate (Depo Provera) for sex offenders
  2. 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.

  1. The flare phenomenon can be effectively prevented with antiandrogen therapy, which blocks the effect of the increased serum testosterone.
  2.  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
  3. 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.
  4. 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.


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


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

1. Inhibit the release of LHRH from the hypothalamus, thus suppressing pituitary LH  release and thereby reducing testosterone.

2. High estrogen levels can lower serum testosterone to castrate levels in one to two weeks.

 3. Estrogens are associated with impotence, loss of libido, and lethargy.

4. Estrogens may help prevent bone loss, even in low doses (eg, DES 1 mg per day).


1. Increase in the incidence of cardiovascular events, including myocardial infarctions, cerebrovascular accidents, and pulmonary emboli.

 2. A dose of 3 mg per day is required to maintain castrate levels of testosterone, but cardiovascular toxicity remains prohibitive with this dose.

3. The availability of GnRH agonists, which do not have the excess cardiovascular morbidity seen with DES, led to the decreased use of DES.

 4. Other estrogens and progesterones include conjugated estrogens, ethinyl estradiol, chlorotrianisene and medroxyprogesterone acetate.

 5. A formulation of conjugated estrogens (Premarin) is Premarin (1.25 mg) either once or three times daily.

  6. Transdermal estradiol is associated with castrate levels of testosterone.

 Dr KK Aggarwal

Padmashri and Dr B C Roy National Awardee

T@ DrKKAggarwal

Face Bok Krishan Kumar Aggarwal

eMedinewS Editorial

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Broccoli compound may combat COPD

In chronic obstructive pulmonary disease (COPD), damage to immune cells limits the lungs’ ability to fight off bacterial infections. According to a new study, boosting the activity of a specific molecule in these cells can restore their defensive powers. In patients with COPD, immune cells called macrophages lose their ability to engulf and remove bacteria, making the lungs more vulnerable to infection. Until now, no one knew how to reverse this damage to the macrophages.

A team of scientists at Johns Hopkins University, led by Drs. Shyam Biswal and Robert Wise, investigated why macrophages don’t work properly in COPD patients. Previous research suggested that a process called oxidative stress might be to blame. Oxidative stress occurs when the body can’t effectively neutralize damaging compounds called peroxides and free radicals.

A molecule called Nrf2 can cause cells to make more antioxidants, which neutralize these harmful compounds. Previous studies found reduced Nrf2 activity in severe COPD. The scientists suspected that increasing Nrf2 activity might restore the ability of macrophages to remove bacteria. To test their theory, the team used a chemical called sulforaphane, which is known to activate Nrf2. A precursor of sulforaphane is found in broccoli. The research was cosponsored by NIH’s National Heart, Lung and Blood Institute (NHLBI) and National Institute of Environmental Health Sciences (NIEHS). The results appeared in the April 13, 2011, issue of Science Translational Medicine.

The researchers first took macrophages from the lungs of patients with moderate COPD. When they treated these macrophages with sulforaphane, they saw higher Nrf2 levels in the cells. Sulforaphane treatment also boosted the ability of cultured macrophages to clear 2 of the major types of bacteria that infect COPD patients. Macrophage uptake of bacteria rose 300% after treatment, whether the cells came from smokers or non–smokers. Experiments in mouse and human cells revealed that sulforaphane, through Nrf2, increases levels of a receptor called MARCO on macrophages. MARCO activity was necessary for macrophages to engulf bacteria after sulforaphane treatment. Mice exposed to smoke had lower levels of MARCO. Furthermore, smoke-exposed mice genetically engineered to lack Nrf2 had more lung inflammation and higher levels of bacteria.

The team gave sulforaphane with a nebulizer to mice exposed to smoke and found that the mice’s lungs showed reduced inflammation and bacterial burden. The researchers also gave human COPD patients broccoli sprout extract enriched with sulforaphane for 2 weeks. The patients taking the extract had higher levels of MARCO and Nrf2–controlled antioxidants in their blood cells. A NHLBI–sponsored clinical trial is now being conducted to test if sulforaphane can provide relief to patients with COPD. (Source NIH)

Dr KK Aggarwal
Editor in Chief