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Med Hypotheses. 2007;69(1):104-12. Epub 2007 Jan 17.
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Is lipid lowering treatment aiming for very low LDL levels safe in terms
of the synthesis of steroid hormones?
Kanat M, Sipahioglu M, Arinc H, Serin E, Yildiz O, Tunckale A, Celebi H.
Abant Izzet Baysal University, Bolu Izzet Baysal Medical Faculty,
Department of Internal Medicine, Golkoy, 14280 Bolu, Turkey.
mustafa.kanat@gmail.com
Today atherosclerotic diseases are among the most important causes of
death in the world. Epidemiological, clinical, genetic, experimental and
pathological studies have clearly shown the role of lipoproteins in
atherosclerosis. LDL is the major atherogenic lipoprotein and has been
defined as the primary target of lipid lowering treatment by NCEP.
Although the level of LDL, the primary target in the treatment of
dyslipidemia, has been set as below 100 mg/dl in coronary heart diseases
(CHD) and CHD risk equivalents, this level has been pulled down to below
70 mg/dl for the group defined as very high risk group by the ATP (Adult
Treatment Panel) guide that has been updated following the new clinical
studies. As we already know, cholesterol is the precursor of
glucocorticoids, mineralocorticoids and sex steroids, besides being a
structural component of the cell membrane. Both adrenal and non-adrenal
(ovarian+testicular) all steroid hormones are primarily synthesized
using the LDL-cholesterol in the circulation. In addition to this, there
is 'de novo' cholesterol synthesis in both the adrenals and gonads
controlled by the HMG-CoA reductase enzyme. A third pathway, which under
normal circumstances has little contribution as compared to the first
two, is the use of circulatory HDL-cholesterol by the adrenal and
gonadal tissues for the synthesis of steroids. Our knowledge on
extremely lowered LDL levels is quite limited. However, since statins
both decrease circulatory LDL and inhibit de novo cholesterol synthesis,
they are likely to affect the synthesis of steroid hormones.
PMID: 17234355 [PubMed - indexed for MEDLINE]
Pharmacotherapy. 2006 Aug;26(8):1165-8. Links
Golf-inhibiting gynecomastia associated with
atorvastatin therapy.
Hammons KB, Edwards RF, Rice WY.
Moses Cone Health System, Greensboro, North Carolina, USA.
Gynecomastia can have a significant emotional and social impact on men.
Although numerous drug therapies may cause this condition, we found no
documented cases of gynecomastia associated with atorvastatin. We
describe the development of breast enlargement and tenderness in a
52-year-old Caucasian man 6 months after his simvastatin therapy had
been switched to atorvastatin. His symptoms ultimately interfered with
his ability to play golf and participate in other activities. These
problems resolved after atorvastatin discontinuation and did not recur
despite resumption of simvastatin therapy. The gynecomastia in this
patient represented a possible adverse effect of atorvastatin according
to the Naranjo adverse drug reaction probability scale. The mechanism
may be atorvastatin's theoretical suppression of adrenal or gonadal
steroid production through effects on cholesterol synthesis. Based on
this and other case reports, 3-hydroxy-3-methylglutaryl coenzyme A
reductase inhibitors (statins) should be considered as a potential cause
when evaluating otherwise unexplainable cases of gynecomastia in
patients taking these drugs.
PMID: 16863492 [PubMed - indexed for MEDLINE]
Ann Pharmacother. 2007 Jan;41(1):138-42. Epub 2007 Jan 2. Links
Probable statin-induced testicular pain.
Linnebur SA, Hiatt WH.
Department of Clinical Pharmacy, University of Colorado at Denver and
Health Sciences Center, Denver, CO 80262, USA.
sunny.linnebur@uchsc.edu
OBJECTIVE: To describe a case of a patient experiencing testicular pain
on 3 occasions after taking 3 different statins. CASE SUMMARY: A
54-year-old man with hyperlipidemia was started on lovastatin therapy.
His other medications included
aspirin,
levothyroxine,
buspirone, and
atenolol. Seven months after starting lovastatin, the patient
experienced testicular discomfort that resolved upon discontinuation of
the drug. Afterward, he started simvastatin and again experienced
testicular discomfort. The simvastatin was changed to atorvastatin, and
the pain resolved. However, 3 months after starting atorvastatin, the
patient developed testicular pain, which resolved after the drug was
stopped. During each of the episodes, the patient's pain increased when
he was sitting, driving, or wearing tight clothing. The Naranjo
probability scale indicates that statins probably caused the patient's
pain. DISCUSSION: Testicular pain is rarely caused by medications.
Product labeling for statins does not list urinary adverse events as
common. However, labeling for atorvastatin and pravastatin lists rare
urologic adverse effects. A literature search did not reveal any
previously reported cases of testicular adverse effects from statins.
However, statins have been shown to inhibit cholesterol synthesis in the
testis. Some data indicate that statins reduce serum testosterone
concentrations, but other data indicate that statins have no effect on
sex hormones or spermatogenesis. Data are also available indicating that
aspirin might affect testosterone concentrations and testicular
function. It is difficult to know whether either of the above hormonal
mechanisms was associated with our patient's testicular discomfort, but
the time course and challenge/rechallenge aspects of the case suggest
that the statins were the cause. CONCLUSIONS: Urologic adverse effects
of statins rarely occur but should not be overlooked by medical providers.
PMID: 17200428 [PubMed - indexed for MEDLINE]
JOP. 2004 Nov 10;5(6):502-4. Links
Recurrent acute pancreatitis possibly induced by atorvastatin and
rosuvastatin. Is statin induced pancreatitis a class effect?
Singh S, Nautiyal A, Dolan JG.
Department of Internal Medicine, Unity Health System, Rochester, NY
14626, USA.
ssingh@unityhealth.org
CONTEXT: Few data exist about the incidence of drug-induced pancreatitis
in the general population. Drugs are related to the etiology of
pancreatitis in about 1.4-2% of cases. While statins are generally well
tolerated they have been known to be associated with pancreatitis. Acute
pancreatitis has been reported in a few cases treated with atorvastatin,
fluvastatin, lovastatin, simvastatin and pravastatin. CASE REPORT: We
report the case of a 77-year-old patient who developed acute
pancreatitis after treatment with rosuvastatin, which resolved on
withdrawal of the medication. She had a similar episode of pancreatitis
a year ago precipitated by atorvastatin, which resolved on withdrawal.
Extensive workup on both occasions failed to reveal any other etiology
for the pancreatitis. CONCLUSION: To our knowledge this is the first
report of rosuvastatin-induced pancreatitis. The occurrence of
pancreatitis with two different statins in our patient argues that
statins induced pancreatitis may be a class-effect of statins. With
statin prescriptions on the rise clinicians need to be aware of this
complication of statin treatment and remember that the newest statin,
rosuvastatin is not dissimilar to the other statins in causing pancreatitis.
PMID: 15536291 [PubMed - indexed for MEDLINE]
J Clin Endocrinol Metab. 2007 Feb;92(2):456-61. Epub 2006 Nov 14.Click
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Effects of simvastatin and oral contraceptive agent on polycystic
ovary syndrome: prospective, randomized, crossover trial.
Banaszewska B, Pawelczyk L, Spaczynski RZ, Dziura J, Duleba AJ.
Department of Gynecology/Obstetrics, Poznan University of Medical
Sciences, Poznan, Poland.
CONTEXT: Polycystic ovary syndrome (PCOS) is associated with
hyperandrogenism and cardiovascular risks including dyslipidemia and
systemic inflammation. In vitro, statins decrease proliferation and
steroidogenesis of ovarian theca-interstitial cells. OBJECTIVE: The
study objective was to compare effects of two treatments of PCOS:
simvastatin plus oral contraceptive pill (OCP) vs. OCP alone. DESIGN: In
a prospective, crossover trial, 48 women with PCOS were randomized to
either simvastatin plus OCP for 12 wk followed by OCP alone for an
additional 12 wk, or to OCP alone for 12 wk and, subsequently,
simvastatin plus OCP for an additional 12 wk. Evaluations were performed
at baseline, after 12 wk (crossover), and after 24 wk. Data were
analyzed using a random effects model. SETTING: The study was conducted
in an academic medical center. Primary Outcome: Serum total testosterone
was the primary outcome measure. RESULTS: Total testosterone decreased
by 38% after Statin + OCP, whereas OCP alone led to a 26% decrease; the
statin-attributable effect was significant (P < 0.004). Free
testosterone declined by 58% after Statin + OCP, significantly more than
the 35% decline after OCP alone (P = 0.006). Hirsutism decreased by 8.1%
after Statin + OCP, a greater effect than the 4.7% decrease after OCP
alone (P = 0.02). Statin decreased LH, but not FSH or prolactin. Statin
+ OCP decreased total and low-density lipoprotein cholesterol by 7.5%
and 20%, respectively. OCP alone led to a 5% increase of total
cholesterol without effect on low-density lipoprotein cholesterol.
Statin prevented OCP induced increase of triglycerides. C-reactive
protein decreased by 45% after Statin + OCP, a significantly different
effect (P = 0.006) than a 6% increase after OCP alone. Soluble vascular
cell adhesion molecule 1 decreased by 18% after Statin + OCP, a greater
decline than the 10% decrease after OCP alone (P = 0.01). CONCLUSIONS:
Simvastatin improved endocrine/clinical aspects of PCOS and had
beneficial effects on lipid profile and markers of systemic inflammation.
PMID: 17105841 [PubMed - indexed for MEDLINE]
More on serious, damaging and seldom discussed damaging effects ofstatins and LDL targets 
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