Vitro symptoms and conditions

I started taking Femcon FE on the 4th of March because my fertility doctor had free samples of it and I only need it for one month before my first in vitro cycle. Today will be the 10th day that I took it and I had to call my doctor because I started getting horrible headaches on my 7th day taking it. It was so bad that I would start crying and my husband would just put his hand on my head to try to make it better. I have a high pain tolerance, so this is not normal for me. I also am exhausted ALL the time. I've had to take like 2-4 hour naps a DAY! Not cool. My doctor immediately told me to stop taking them as the headaches like that is not normal. I have to wait a couple days till I start my period again and then they will put me on just estrogen until I'm ready for the cycle. I know that all BC pills have side effects, but these are horrible and I've heard so many horror stories about it already that it kind of gives me major red flags about it. Just beware if you want to try it. I took Ortho Tri Cyclin 8 years ago when I needed the BC pill and I don't remember having ANY side effects at all.

Since HTML is not allowed...need you to find the links to the following:

"whether an oral contraceptive (OC) containing drospirenone (DRSP) (3 mg) + ethinyl estradiol (EE) (30 μg) (DRSP + EE) could modify psychological symptoms and whether it could modify steroids interfering with the γ-aminobutyric acid (GABA)-A receptors.

Conclusion(s): The results suggest beneficial effects of DRSP + EE on psychological symptoms by

decreasing DHEAS."

Beneficial to lower the levels of DHEAS?!

"Women With Higher Levels Of DHEAS Have Better Cognitive Function"

"dehydroepiandrosterone sulfate (DHEAS), inhibit the production of TNF in vitro and in vivo."

Who is at greater risk?

Those who have the HLA-DR gene type and already have allergies/asthma.

Adrenergically blockaded conditions = AdBCs include the following: respiratory allergies, skin allergies, and asthma.

IgE will go thru the roof. Allergic reaction. Th2 pathway.

""It has also been shown that young women exposed to intensive stress situations,

with low plasma of dehydroepiandrosterone
sulfate (DHEA-S),

and a recent use of contraceptive pills are most at risk for

onset of autoimmune disease."

Clinical trial of montelukast in the Netherlands.

I noticed two things:

1. The researcher states that sides effects are 10%.
2. The researcher will not allow patients to also take drugs which are metabolized by CYP2C8 because montelukast inhibits that as proved by in vitro (test tube) studies. American studies in vitro said yes montelukast is an inhibitor but in vivo (in people) that it didn't happen. I was always confused by that and would still like to know more
.
******

Hopefully this will prove to the doubters that there are genetic reasons for the variation of efficacy and adverse side effective when taking Montelukast.

I have several areas of concern (concerned citizen is concerned). One of the main areas is the reliability of Montelukast due to differences in genetics among populations. The cysLT1 (Singulair) receptor is a GENE. As I said before, it would be possible to predict those patients for which Montelukast would and would not be effective and those patients whose gene expression profile would cause them to have unwanted side effectives.

I have been looking for a way to give reasonable proof of that which could be used to convince your doctors that Montelukast is not for everybody. I happened to locate a researcher who had invented and patented methods for predicting drug sensitivity and efficacy in inflammatory disease. I have quoted below from his patent application. He intended to provide a method for determining efficacy and drug sensitivity for pharmaceuticals which include leukotriene antagonists - Montelukast.

Quoted from:

Methods for predicting drug sensitivity in patients afflicted with an inflammatory disease
US Patent Issued on December 12, 2006

Methods are disclosed for predicting the efficacy of a drug for treating an inflammatory disease in a human patient, including: obtaining a sample of cells from the patient; obtaining a gene expression profile of the sample in the absence and presence of in vitro modulation of the cells with specific cytokines and/or mediators; and comparing the gene expression profile of the sample with a reference gene expression profile, wherein similarities between the sample expression profile and the reference expression profile predicts the efficacy of the drug for treating the inflammatory disease in the patient.

-----------------------------------------------------------
The field of pharmacogenomics measures differences in the effect of medications that are caused by genetic variations. Such differences are manifested by differences in the therapeutic effects or adverse events of drugs. For most drugs, the genetic variations that potentially characterize drug-responsive patients from non-responders remain unknown.
---------------------------------------------------------

In another embodiment, the invention is directed to a method for predicting the efficacy in a human asthma patient of leukotriene antagonists including, but not limited to, montelukast (a.k.a., SINGULAIR™; Merck, Whitehouse Station, N.J.), zafirlukast (a.k.a., ACCOLATE™, AstraZeneca, Wilmington, Del.), and zileuton (a.k.a., ZYFLO™; Abbott Laboratories, Chicago, Ill.), comprising: obtaining a sample of cells from the patient; obtaining a gene expression profile from the sample in the absence and presence of in vitro modulation of the cells with specific mediators; and comparing the gene expression profile of the sample with a reference gene expression profile, wherein similarity in expression profiles between the sample and reference profiles predicts the efficacy in the human asthmatic patient of leukotriene antagonists.

Many of the cells involved in causing airway inflammation are known to produce signaling molecules within the body called "leukotrienes." Leukotrienes are responsible for causing the contraction of the airway smooth muscle, increasing leakage of fluid from blood vessels in the lung, and further promoting inflammation by attracting other inflammatory cells into the airways. Oral anti-leukotriene medications have been introduced to fight the inflammatory response typical of allergic disease. These drugs are used in the treatment of chronic asthma. Recent data demonstrates that prescribed anti-leukotriene medications can be beneficial for many patients with asthma, however, a significant number of patients do not respond to anti-leukotriene drugs.

--------------------------------------------------

The genes selected are those that have been determined to be differentially expressed in either a disease, drug-responsiveness, or drug-sensitive cell relative to a normal cell and confer power to predict the response to the drug. By comparing tissue samples from patients with these reference expression profiles, the patient's susceptibility to a particular disease, drug-responsiveness, or drug-resistance can be determined.

http://www.patentstorm.us/patents/7148008-description.html

The inventor's website: Hakon Hakonarson M.D. The Children's Hospital of Philadelphia

http://stokes.chop.edu/research/profiles/?ID=251

Singulair does interact with the astrocyte in the brain.

The role of the cysLT1 receptor (Singulair blocks this receptor) and the astrocyte in the brain has been studied. For anyone from Merck to say that there are no mechanisms by which Singulair can affect the
brain is ludicrous. If the Chinese researchers are correct, then Singulair very clearly affects the brain. Certainly, we don't know exactly how or when the effect would be good or bad. Under what circumstances would it be beneficial and under what circumstances would it be harmful.

For quite a while, researchers have been hypothesizing about the role of the astrocyte in brain function. If we go to look for theories, we will find them. Here is the theory of Dr. Dale Antanitus. I am no here to promote anyone's theory in particular but just to point out that they exist.

http://www.antanitus.com/hypothesis

We can see that the Chinese researchers have gone forward to look at potential links between the cysLT1 receptor (Singulair receptor) and inflammatory response in the brain. The 2008 study showed a link between the astrocyte and the cysLT1 receptor (Singulair receptor)

1: Glia. 2008 Jan 1;56(1):27-37. Links
Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation.

Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, People's Republic of China.

We recently found that 5-lipoxygenase (5-LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT(1) and CysLT(2) receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5-LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen-glucose deprivation (OGD) followed by recovery to induce ischemic-like injury in the cultured rat astrocytes. We found that 1-h OGD did not injure astrocytes (sub-lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4-h OGD moderately injured the cells (moderate OGD) and led to death 24-72 h after recovery. Inhibition of phospholipase A(2) and 5-LOX attenuated both the proliferation and death. Sub-lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5-LOX inhibitors. Sub-lethal OGD increased the expressions of CysLT(1) receptor mRNA and protein, while moderate OGD induced the expression of CysLT(2) receptor mRNA. Exogenously applied leukotriene D(4) (LTD(4)) induced astrocyte proliferation at 1-10 nM and astrocyte death at 100-1,000 nM. The CysLT(1) receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT(2) receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD(4) (100 nM) increased the expression of CysLT(2) receptor mRNA. Thus, in vitro ischemia activates astrocyte 5-LOX to produce CysLTs, and CysLTs result in CysLT(1) receptor-mediated proliferation and CysLT(2) receptor-mediated death. (c) 2007 Wiley-Liss, Inc.

PMID: 17910051

The astrocyte has been studied to see how it functions in the brain. The astrocyte:

1. may perform a role in the physical structuring of the brain
2. may perform a role in providing neurons with nutrients
3. may perform a minor role in the maintenance of the blood brain barrier
4. may perform a role in neurotransmitters
5. may perform a role in the regulation of ion concentration in the extracellular spaces
6. may perform a role in neuronal regulation of blood flood
7. may perform a role in the protection and repair of neurons

TO LIE TO PEOPLE REGARDING THEIR HEALTH IS CRIMINAL AND SHOULD BE PROSECUTED. PEOPLE OUT THERE ARE GETTING SICKER IF THEY ARE EXPERIENCING SIDE EFFECTS BECAUSE MERCK IS LYING. SOME PEOPLE MAY NOT EXPERIENCE SIDE EFFECTS BUT WHY NOT TELL THE TRUTH AND SAY THAT THERE COULD BE SOME PEOPLE WHO HAVE PSYCHIATRIC SIDE EFFECTS BECAUSE THERE IS A PATHWAY FOR THAT TO HAPPEN.

Here is one for you Artie. Maybe you can go find the statistical profile of studies regarding montelukast and CYP2C8. Originally it was hypothetized that montelukast would inhibit CYP2C8 thus inhibiting steroid (as an example) metabolize. In vitro studies predicted that. Then studies in vivo didn't confirm. Here is another one done in 2006.

Conclusions: Telithromycin increases the plasma concentrations and blood glucose–lowering effect of repaglinide by inhibiting its CYP3A4-catalyzed biotransformation and may increase the risk of hypoglycemia. Unexpectedly, montelukast has no significant effect on repaglinide pharmacokinetics, suggesting that it does not significantly inhibit CYP2C8 in vivo. The low free fraction of montelukast in plasma may explain the lack of effect on CYP2C8 in vivo, despite the low in vitro inhibition constant, highlighting the importance of incorporating plasma protein binding to interaction predictions.

http://www.nature.com/clpt/journal/v79/n3/abs/clpt2006320a.html

The question would be is that always the case or are there genetic variations among people that influence the outcome? Or is there potentially something else that we should be recognizing and we aren't doing that.

I thought of that again when I read this post. We obviously have many questions that should be answered especially when something that we don't expect happens.

Posted by Mindy Miller
Monday, April 14, 2008 4:39 AM EST

I am a pharmacy student and a mother of two sons that take Singular daily. My six year old has been taking it for 4 years, and my three year old for two years. They both have well controlled asthma. I wanted to reply to the questions many have posted about how long it takes to "get out of your system". The half life of Singular is 3-6 hours, so it is gone in a maximum of 18 hours. I came to this website while searching for information about recent FDA warnings. As far as I can tell, there are very few cases documented of mood changes and suicidal thoughts. There are many reasons why children have mood changes, and not feeling well because they have asthma and allergies could also be the source. I wonder if many who start Singular are also taking Prednisone, a steroid, to treat an asthma flare up. Steroids are definitely known to cause mood changes and is one of the reasons they can't be used long term. Please talk to your doctor or pharmacist before taking your children off of medication that may be helping them feel better in the long run.

http://www.injuryboard.com/national-news/fda-issues-early-warning-on-singulair-and-suicides.aspx?googleid=30278

If we had all of the answers, then there would not be such a wide range of symptoms that manifest themselves as a result of Singulair. So I am not trying to spread any conclusions that may be misleading. These are questions and not answers.

I've been scared into a tizzy by the reports of side effects, many dangerous or long-lasting, and wondering if anyone reading has experience with the use of lupron for in vitro or similar reproductive assisting technology. By my calculation, the equivalent of a monthly 3.75 mg dose for endometriosis is exceded on the eighth day of daily .1cc injections before IVF. Any advice would be most welcome! Thank you.