Science Doing: Androgen deprivation-hormone therapy for adenocarcinoma prostate

Androgen regulation in human body

The hypothalamus coordinates many hormonal and behavioural circadian rhythms, complex patterns of neuroendocrine outputs, complex homeostatic mechanisms, and important behaviours.

Gonadotropin-releasing hormone	GnRH or LHRH	Neuroendocrine cells of the Preoptic area	Stimulate follicle-stimulating hormone (FSH) release from anterior pituitary Stimulate luteinizing hormone (LH) release from anterior pituitary

Human hypothalamus (animation, shown in red)

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Pituitary gland is an endocrine gland about the size of a pea and weighing 0.5 grams (0.018 oz) in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The pituitary gland is functionally connected to the hypothalamus by the median eminence via a small tube called the infundibular stem (Pituitary stalk). The pituitary gland secretes nine hormones that regulate homeostasis.

Located at the base of the brain,

the pituitary gland is protected

by a bony structure called the

sella turcica of the sphenoid bone.

courtesy share: http://en.wikipedia.org

Pituitary gland
courtesy share: http://en.wikipedia.org

Gonadotropins:

Luteinizing hormone (also referred to as 'Lutropin' or 'LH' or, in males, 'Interstitial Cell-Stimulating Hormone' (ICSH))

Follicle-stimulating hormone (FSH), both released under influence of Gonadotropin-Releasing Hormone (GnRH)

These hormones are released from the anterior pituitary under the influence of the hypothalamus. Hypothalamic hormones are secreted to the anterior lobe by way of a special capillary system, called the hypothalamic-hypophysial portal system.

Hormone therapy for adenocarcinoma prostate

Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy. The goal is to reduce levels of male hormones, called androgens, in the body, or to prevent them from reaching prostate cancer cells.

The main androgens are testosterone and dihydrotestosterone (DHT). Androgens, which are made mainly in the testicles, stimulate prostate cancer cells to grow. Lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancers shrink or grow more slowly for a time.

Types of hormone therapy

Several types of hormone therapy can be used to treat prostate cancer.

Orchiectomy (surgical castration)

Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles (bilateral orchiectomy), where most of the androgens (testosterone and DHT) are made. With this source removed, most prostate cancers stop growing or shrink for a time.

GnRH blockers

Gonadotrophin-releasing hormone (GnRH) antagonists (receptor blockers) are a class of compounds that are similar in structure to natural GnRH (a hormone made by neurons in the hypothalamus ) but that have an antagonistic effect. GnRH antagonists are peptide molecules that are made up multiple, often synthetically produced amino acids. GnRH antagonists compete with natural GnRH for binding to GnRH receptors, thus decreasing or blocking GnRH action in the body.

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. The chemical name is 5oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula:

In adults, leuprolide may weaken your bones and increase your risk for bone loss (osteoporosis) if used for a long time because it reduces estrogen...

Luteinizing hormone-releasing hormone (LHRH) analogs (blockers)

These drugs lower the amount of testosterone made by the testicles. Treatment with these drugs is sometimes called chemical castration because they lower androgen levels just as well as orchiectomy.

Even though LHRH analogs (also called LHRH agonists) cost more than orchiectomy and require more frequent doctor visits, most men choose this method. These drugs allow the testicles to remain in place, but the testicles will shrink over time, and they may even become too small to feel.

When LHRH analogs are first given, testosterone levels go up briefly before falling to very low levels. This effect is called flare and results from the complex way in which LHRH analogs work.

Anti-androgens

Anti-androgens block the effect of adrenal gland hormone as well as testicular androgens by interfering with a receptor in the nucleus of the prostate cancer cells.
So anti-androgens block the body's ability to use any androgens. Even after orchiectomy or during treatment with LHRH analogs, the adrenal glands still make small amounts of androgens.

Drugs of this type, such as flutamide (Eulexin^®), bicalutamide (Casodex^®), and nilutamide (Nilandron^®), are taken daily as pills.

Anti-androgens are not often used by themselves. An anti-androgen may be added to treatment if orchiectomy or an LHRH analog is no longer working by itself. An anti-androgen is sometimes given for a few weeks when an LHRH analog is first started to prevent a tumor flare.

Anti-androgen treatment may be combined with orchiectomy or LHRH analogs as first-line hormone therapy. This is called combined androgen blockade (CAB).

Duprost is a 5 alpha-reductase enzyme inhibitor. It works by lowering levels of a hormone called dihydrotestosterone (DHT), which is a major cause of prostate growth. Lowering DHT leads to shrinkage of the enlarged prostate gland, reducing the risk of urinary blockage and need for prostate surgery. Duprost (Dutasteride) is used to treat symptoms of benign prostatic hyperplasia.

Silofast (8 mg) - Capsule, manufactured by Cipla Limited contains Generic Medicine Silodosin- 8 mg.Used for the symptomatic treatment of benign prostatic hyperplasia.

Treatment results after the first three month medication as above:

For Post void residual urine volume (PVRUV): changes occurred from 502 cc to 381.53 cc

For weight of the prostate gland: This almost remained the same