Wednesday, November 14, 2012

Post-Finasteride Syndrome


Post-Finasteride Syndrome is the set of symptoms presented by men who took Finasteride 1mg for hair loss, stopped taking the medicine, and their bodies did not return to previous state. Even after years. This drug caused changes in their metabolic and endocrine systems, as well as it may have caused uunknown biochemical changesThere are, however, numerous cases where the patient's hormonal tests are completely normal (with the exception of androstanediol glucuronide), and he has the classic symptoms of Post-Finasteride Syndrome . There are ongoing studies in the U.S. and Europe, and trying determine whether these patients developed some degree of androgen insensitivity after using finasteride. This androgen insensitivity theory would explain why men having persistent propecia (finasteride) side effects do not benefit from testosterone replacement therapy. In these men, TRT did not cause any benefit, any sexual or mental improvement. Even when they were put on supraphysiological levels of testosterone. So according to the androgen insensitivity theory, these men could have become somehow immune to the benefits of the main male hormone.


The way finasteride causes post finasteride syndrome in certain individuals is unknown. Finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT), but also causes changes in testosterone levels, LH and FSH. 1 Finasteride also blocks the biosynthesis of various neuro steroids such as allopregnanolone (ALLO) and Tetrahidroteoxicorticosterone (THDOC), which are isoforms of the enzyme 5 alpha reductase. ALLO and THDOC are positive modulators (allosteric modulators) of GABA-A receptors, which have the same mechanism of action of anxiolytic drugs such as benzodiazepines. 2, 3 Finasteride has been shown to inhibit the biosynthesis of these neuro steroids, which can be one of the causes for the emotional and sexual symptoms reported. 4 However, some symptoms, such as muscle wasting, loss of body hair and the continuation of symptoms long after the medication has been discontinued, have not been explained yet. Because some patients with SPF have normal or high levels of testosterone - but at the same time a complete clinical state of hypogonadism - it has been hypothesized that these individuals have developed a form of resistance to androgen hormones. 5

There is research that is ongoing in the US and Europe, and try to determine whether these patients developed some degree of androgen insensitivity after using Finasteride.This androgen insensitivity explain why testosterone replacement in these men, even in supraphysiological doses, caused no sexual or mental benefit. Finasteride would have caused profound changes that have left these 'immune' to testosterone men.

Note: It is not necessary to present all the symptoms that characterize the disease. The vast majority of men who developed the problem has mostly sexual symptoms (and often only some of the sexual symptoms). In more severe cases, the patient developed, in addition to sexual symptoms, neurological, cognitive and physical problems. And there are even more severe cases, patients who had these symptoms worsened and this situation led to other problems:


Sexual Symptoms

Libido:
Loss of sexual interest, lack of sexual thoughts.
Loss of erotic dreams


Erections:

Erectile dysfunction
Loss of morning erections
Lack of spontaneous erections
Lack of nocturnal erections


Penis:

Loss of sensation in the penis
Decrease in size of the erect penis
Peyronie's disease (in some cases)


Testicles and ejaculation:

Decrease in the size of the testicles
Pain in testicles
Decreased volume of ejaculate
Watery ejaculation


Orgasm:

Loss of intensity in orgasms
Difficult to achieve orgasm


Physical Symptoms

Gynecomastia (abnormal growth of breasts in men)
Muscle spasms
Fatigue, constant tiredness
Less acne
Dry skin
Joint pain
Digestive problems


Neurological Symptoms

Loss or decrease in memory capacity compared to before finasteride use
Cognitive difficulties (comprehension problems, difficulty in problem solving, information processing, eg, perform a mathematical operation, memorize a text, learn a foreign language.)
Slurred speech (less common)
Insomnia
Loss or reduction of REM sleep stage (no dreams, lighter sleep)
Loss of excitement with aspects of life, indifference
Loss of motivation, ambition,
Depression, melancholy,
Extreme anxiety, panic attacks



What hormones, enzymes and neurotransmitters  are affected in the post Finasteride Syndrome?



Men affected by the "SPF" have changes in hormones following:

- Total Testosterone -
below what would be expected for the patient's age. In many cases, such low levels that characterize hypogonadism
- LH and FSH -
Low-normal levels of LH and FSH. Similar to secondary hypogonadism. It is possible that finasteride may reduce pituitary activity in some men. As everything in this Syndrome, it is a theory that requires investigation. However, there are studies that show finasteride affects hippocampus. 
- Estradiol -
Many show a high level of the hormone.
-Prolactin-
Some patients present an elevated prolactin level. However, MRI to investigate the possibility of prolactinoma shows no abnormality.
Androstanediol-glucuronide (3 adiol G) -
Androstanediol glucoronide is a hormone derived from DHT (the hormone inhibited by finasteride). In men affected by the PFS, the level of Androstanediol Glucuronide is not restored to previous finasteride levels. The result of the blood test hormone in these patients  is generally below the scale or a very low result . It's unnatural for adult men to have low levels of 3 Adiol G. Only individuals who are born with intersex characteristics (hermaphrodites) have low levels of this hormone. It is essentially a masculinizing hormone and may have an effect on sexuality (science still knows very little about it). Women present low levels of Androstanediol Glucoronide naturally, since they produce little testosterone. Women who have high levels of this hormone, show reproductive problems (polycystic ovary), excess body hair and a more masculine appearance.

-TSH-
Some patients also have changes in TSH. There are cases where the Post-Finasteride Syndrome induced hypothyroidism. However, it is not most cases.
-Progesterone-
As finasteride inhibits the conversion of progesterone to allopregnanolone by blocking the enzyme 5-alpha reductase, a higher level of progesterone is also possible in these patients.


Other tests: 
Vitamin-D -

Many PFS patients have low levels of Vitamin D.
- Cholesterol -
PFS Patients may present high or very high cholesterol.


Other possible alterations: 
- Zinc -

There are speculations that the level of zinc has also been affected in these patients.
-Dopamine-
There are concerns Finasteride  may reduce the production of dopamine in these patients. The drug manufacturer has added depression as a possible side effect of this medication. A large decrease in the level of dopamine in these patients may also help explain the emergence of some sexual symptoms.
- Allopregnanolone-
Produced from the conversion of Progesterone by the enzyme 5alpha-reductase , Allopregnanolone is a tranquilizer found in the brain. Allopregnanolone acts to modulate GABA-A in brain. There is evidence in studies that the level of allopregnanolone in these patients have been altered by finasteride.
- Changes in immune system, possibly aggravated by the sharp decline in testosterone level.
Recent studies indicate that testosterone plays an important role in regulating the immune system in men. As these men may present a large decrease in testosterone levels, it is plausible to relate the fact to changes in their immune systems. There are reports of patients with the syndrome who have developed food or skin allergies or skin, which they did not have before using Propecia (finasteride).
Patients also report changes in how the body reacts to inflammation.
- Excess Cortisol release 
Virtually all reports of patients suffering from Post-Finasteride Syndrome have a description of what they call Post Finasteride crash. This endocrine crash usually occurrs a few days or weeks after the cessation of treatment with 1 mg finasteride in these patients. They report very high stress symptoms, which often develops into an episode of panic attack or anxiety attack. Another related symptom is insomnia or light and disturbed sleep. It is worth mentioning here that these patients showed these symptoms of acute stress, before they learned about the Post-Finasteride Syndrome or the possibility of lingering effects related to finasteride, thus eliminating the possibility of placebo effect or psychosomatic effect.


Theories being investigated in Europe and the United States:



a) Finasteride would have shut down a gene in subjects genetically prone to this problem. (That would explain why some men develop the problem and others do not)
b) Finasteride would have bound to the androgen receptors, preventing these hormones to exert their function and it this would be a type of androgen insensitivity
c) Finasteride would have affected the level of free cortisol in the body. Cortisol is necessary to increase the efficiency of all functions in the body. So even if the individual shows normal results on thyroid hormone blood tests, cortisol deficiency could induce similar symptoms to hypothyroidism.


Sources:
1) Uygur MC, Arik AI, Altuğ U, Erol D.: Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of gonadal, adrenal, and hypophyseal hormones and its clinical significance: a prospective clinical study.
2) Römer B, P Gass (December 2010). "Finasteride-induced depression: new insights into possible pathomechanisms."Journal of Cosmetic Dermatology 9 (4): 331-332. doi: 10.1111 / j.1473-2165.2010.00533.x 
3) BG Gunn, Brown RA, Lambert JJ, Belelli D (2011). "Neurosteroids and GABA (A) Receptor Interactions: A Focus on Stress." Frontiers in Neuroscience 5: 131. doi: 10.3389 / fnins.2011.00131. PMC 3.23014 million. 
4) DA Finn, AS Beadles-Bohling, EH Beckley, MM Ford, KR Gililland, RE Gorin-Meyer, KM. Wiren: A new look at the 5alpha-reductase inhibitor finasteride. 
5) Rose Hartzell: Changes in Men's Sexual, Emotional, and Cognitive Functioning after taking Finasteride For Hair Loss. In: The Journal of Sexual Medicine, Special Issue, Proceedings of the World Meeting on Sexual Medicine, Chicago, USA, 26.-30. August 2012, doi: 10.1111 / jsm.2012.9.issue-s4