top of page

Statins, cholesterol and erectile dysfunction - 21

Summary:


  • Cholesterol is needed to produce testosterone, other sex hormones, and hormones in general.

  • Statins generate calcifications that reduce blood flow. (see previous blog)

  • LDL carries important fats and the actual cholesterol molecule necessary for sperm production. (see previous blog)

  • Statins reduce LDL, thus reduce sperm production.


Note: the word cholesterol is NOT in quotes. In this case, the studies refer to the actual cholesterol molecule. Statins lower LDL, thus lower transport of the cholesterol molecule.


 

Cholesterol is essential for mammalian cell functions and integrity. It is an important structural component maintaining the permeability and fluidity of the cell membrane. The balance between synthesis and catabolism of cholesterol should be tightly regulated to ensure normal cellular processes. Male reproductive function has been demonstrated to be dependent on cholesterol homeostasis.


Here we review data highlighting the impacts of cholesterol homeostasis on male fertility and the molecular mechanisms implicated through the signaling pathways of some nuclear receptors.


There is an intimate association between cholesterol metabolism and fertility during spermatogenesis. Cholesterol is required for the mass production of germ cells during spermatogenesis. A study determined that cholesterol de novo synthesis was increased during the development of pachytene, leptotene, and zygotene stages (98), which was associated with increased diameter and surface area of germ cells.


Like any animal cell, spermatozoa have a lipid bilayer plasma membrane. The proportion of the different constituents gives to the spermatic plasma membrane unique properties. The spermatic membrane has been shown to be rich in polyunsaturated fatty acids (PUFAs) important for ensuring the viability and mobility of the spermatozoon (101–103).


The high proportion of PUFA also seems to play an important role in the process of membrane fusion between spermatozoon and oocyte. Indeed, PUFAs contribute to flexibility and membrane fluidity (104, 105). The high proportion of PUFA, especially docosahexaenoic acid (DHA) in humans, is important for fertility. Indeed, one study showed a decrease in PUFAs and an increase in saturated fatty acids (SFA) in spermatozoa of asthenozoospermic men compared to sperm of normozoospermic men (106).


Another study also found a negative correlation between body mass index and DHA and a positive correlation between DHA and normal sperm parameters (107). Sterols are the second major components of the plasma membrane. Cholesterol is the most abundant sterol found in the spermatic membrane of many species (102). Spermatozoa are enriched in cholesterol within the seminiferous tubules. Indeed, in the spermatocyte stage, the germ cells are able to synthesize de novo cholesterol to allow the increase of their membrane surface (98).



Sex hormones are steroid hormones that include the progestins, androgens (e.g. testosterone), and estrogens (e.g. estradiol). Like all steroid hormones, they:

  1. are derived from cholesterol

  2. are hydrophobic which means they must be bound to plasma proteins for transport through the bloodstream, and;

  3. bind to cytosolic or nuclear receptors (not surface receptors of the plasma membrane like peptide hormones do).




Cholesterol is an important component of cell membranes, and also a precursor for the synthesis of sex hormones, playing an important role in reproduction. However, few studies have focused on cholesterol and reproductive health.


To investigate the toxic effects of different cholesterol levels on the spermatogenesis of rare minnows, we regulate the cholesterol content in fish by feeding them a high-cholesterol diet and cholesterol inhibitor pravastatin, and cholesterol levels, sex hormone (T and 11KT) levels, testis histology, sperm morphology and function, and the expression of genes related to sex hormone synthesis were investigated.


The research findings indicate that increasing cholesterol levels significantly increases the liver weight and hepatic–somatic index, as well as the total cholesterol and free cholesterol levels in the testis, liver, and plasma of rare minnow, while inhibiting cholesterol has the opposite effect (p < 0.05).


However, both increasing and decreasing cholesterol levels can suppress rare minnow testicular development, as evidenced by a decrease in testis weight, lowered gonadosomatic index, suppressed sex hormone levels, and reduced mature sperm count.



The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia.


The effectiveness of this drug in controlling cholesterol production is impeccable,

however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis.


Not only has the use of statins caused the aforementioned side effects, but they are also shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production.


The negative effects have been associated with imbalanced or reduced steroid hormones, which are necessary for proper spermatogenesis and other sexual functions.


6.4. Rosuvastatin and Male Infertility


6.4.2. Human Findings A case report by Tada et al. showed that rosuvastatin was able to cause reversible azoospermia in a patient seeking fertility treatment. After 16 weeks of withdrawing from rosuvastatin intake, sperm was seen in the semen, making IVF possible [11].


Although clinical trials regarding the effect of rosuvastatin on male fertility are limited, these outcomes indicate that rosuvastatin adversely affected male reproductive parameters during active usage.


6.5. Simvastatin and Male Infertility


Simvastatin is a relatively short-lived statin that is taken at doses of 5–80 mg. In vitro studies have shown that simvastatin affects 17-hydroxy-steroid-dehydrogenase. This enzyme catalyzes the conversion of androstenedione to testosterone which is essential for the production of sperm [53]. Even though in vivo reports of simvastatin on male fertility are scarce, some have attempted to draw significant conclusions between the two.


6.6. Lovastatin and Male Infertility


Although studies that have evaluated the effect of lovastatin on overall male reproductive health are limited, the available findings show that lovastatin reduces steroidogenesis [18,70,71]. For instance, Tobert et al., reported that after administering lovastatin in multiple doses to healthy male volunteers for four weeks, the serum concentration of testosterone and other steroidal hormones was reduced [70].


The same trend of results was also reported by Mcdonald et al., who administered lovastatin in different doses to animals in a preclinical setting [71]. Although more recent studies evaluating these effects are lacking, it is unbiased to say that lovastatin could hamper spermatogenesis if the level of testosterone is drastically and sustainably reduced.


11. Conclusions


Although the influence of statins on fertility is not widely investigated, multiple studies have demonstrated their effects on fertility.

 

Index & Upcoming (short) blogs on cholesterol and statins


Number 1: Cholesterol fun (true) facts - completed

Number 2: Is the actual cholesterol molecule important? c - completed

Number 3: What is an optimal TC value? Remember, no one knows their actual cholesterol molecule value. - completed

Number 4: Surprising fact about cholesterol as an antibiotic - completed

Number 5: TC simple math - dumb doctors - completed

Number 6: What is LDL really? - completed

Number 7: Statins - do they lower the cholesterol molecule? - completed

Number 8: What did we learn from the new "biologics" to lower "cholesterol" - completed

Number 9: Niacin and other "cholesterol" management treatments - completed

Number 10: What did Natasha Campbell-McBride say about cholesterol/lipids? - completed

Number 11: What is a QALY, and how does it relate to "cholesterol"? - completed

Number 12: Idiot doctor from Johns Hopkins, Roger Blumenthal - completed

Number 13: Statins cause Alzheimer's and ALS - THEHIGHWIRE - completed

Number 14: Statin drugs CAUSE diabetes - completed

Number 15: The statin merry-go-round to poor cardiovascular outcomes - completed

Number 16: How statins CAUSE heart disease - completed

Number 17: How statins CAUSE heart disease - part 2 - completed

Number 18: Women and statin drugs - completed

Number 19: If not "cholesterol," then what? - completed

Number 20: If not "cholesterol," then what? - part 2 - completed

Number 21: Statins and erectile dysfunction - completed

Number 22: Who says statins do NOT extend life?





 

Weekly Webinar Links: Join us for detailed health information - at no charge. All are welcome.


Monday at noon EST -


Wednesday at 8 pm EST -

 


Be Bold - Be Brave - Stay Well




 

242 views0 comments

Recent Posts

See All

Comments


bottom of page