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Love and Relationship
How to attract girls
If you know how to attract girls, then chasing women won’t be necessary as they will come to you. When a woman is chasing you instead of the other way around, it is much easier to be relaxed and have a good time instead of concentrating on what to do next. So what attracts people, and more specifically girls ? Things that are out of the ordinary. If you blend in with the rest of the world, then no one will ever notice you walking down the street, or in any location for that matter. How do most people blend ? By following what everyone else does and this leads to catastrophic results when trying to attract women. Being a follower is boring and speaks a lot about your personality. It shows that you are insecure to try new things and that you don’t want attention. Now the trick to being noticed is not to dress up in bright yellow colors, but to add one interesting item to your physical appearance. There are a few guidelines to selecting the proper attire that will attract women without making you look like a fool. First steps to being more attractive.
First, take into consideration what kind of social setting you will be in. If you’re going to a club, then you can go all out with outlandish clothing and accessories. However, if you’re going to the library, it would be more effective to carefully choose one single attention drawing accessory. For clubs, keep in mind that you want to look different than everyone else. If everyone else is dressed up with expensive clothing, then wearing something cheap will work better. You’ll automatically be classified as the ‘guy who doesn’t care’, which can be very attractive. If you’re at a place where people are dressed like bums, then feel free to dress up a little more and you’ll automatically be seen as ‘the only classy guy’ in the place. Sometimes clothing itself can make a large enough difference, however accessories can further improve your magnetism throughout the day. Something unique that represents you is the ideal thing. Let’s say you enjoy biking, then you could have a necklace with a bicycle on it for instance. Then, in a social situation, people will notice and comment on your accessories. The more out-of-the-ordinary your accessories are, the more you will get noticed. However, you must be able to continue the conversation and match the boldness of your accessory with your personality. Once you learned how to attract girls, you’ll need to learn how to keep them. The attitude that you have is more important than all the clothes, money and looks in the world. Its cliche, but personality is more important to women than looks. In fact, there are a few secret techniques that will make you irresistible to women regardless of appearance. One of the most effective techniques is called “Cocky / Funny” in the the Double Your Dating book by David Deangelo. It teaches all the fundamental and advanced ways on how to ATTRACT girls and keep them attracted to you permanently.
Easily Attract Girls at Will!
Picture this, you walking down a street and right in front of you, appears a beautiful girl, blonde hair, blue eyes and a body of Venus. As she gets closer to you she looks up, sees you and gives you a fantastic smile. You turn around thinking is it me she is smiling at, and realise that it is. So what you do? As usual you smile back like a grinning fool, do nothing and just walk on by. Sound familiar? Every man that ever walked the earth at some stage in his life has had an experience not dissimilar to this one. It may have been in a bar, on a bus, in the office or workplace or in any other such social situation. Most men ask the question “was she interested in me” the answer to this question is simple! Of course she was you idiot! In sales they would call this a buying signal and you would move in to sign up the deal.
Fear not, understanding the buying-signals of women is only a part of what you will learn in this book. You will learn insights into understanding yourself and how to make yourself the very essence of attractiveness to women. You will learn how to approach and talk to women in a way that will make you both charming and interesting to the fairer sex. You will learn techniques that would give yourself confidence in your ability to attract women at will. You will also understand what women are looking for in men, and like a chameleon mould yourself into that role to achieve your goal. These techniques are both simple to understand, and easy to apply, in fact you should be able to use and apply these techniques from day one. You will become a powerhouse of pulling, the very essence of charm and desirability to women the world over. Your friends will look at you with awe and envy, and wonder where this rich vane or form came from. You will look back with a knowing smile and say, “what can I say I guess I'm just a regular Don Juan”. Just so that you know, all men can use these techniques. From the athlete, to the nerd, from Brad Pitt to the Elephant man, from the very old to those just starting out on their journey into the mysteries of women. These techniques are timeless and transcend all barriers. I often hear said, “There are never any women around that I find attractive” well guess what yes there are half the population of the world are women! By most people's reckoning that is approximately 3,000,000,000 women for you to choose from. So saying that there is a lack of women to choose from is somewhat ridiculous. With all this opportunity that is out there, just waiting for you to make their day, I think we should begin, don't you! The power of the pulling triangle! Pulling is my local colloquialism, for attracting the ladies in a deliberate manner, you may know it by many other names, picking up, chatting up or even sharking. It does not matter what you call it, as it all amounts to the same thing, your effort in trying to find favour with the fairer sex. As the title suggests, there are three sides or points to the pulling triangle. I will talk about them in a little while, firstly I shall tell you how the pulling triangle was developed, it is rather a silly little tale, but there is no denying the power of this technique. The Idea One summer while in the garden of a friend's house, myself and a couple of other friends were sitting around drinking it was a beautiful day the beer was flowing and as with most single guys our thoughts turned to women. Now you need to understand that the guys who were sitting around this particular table were having varying degrees of success with the ladies. Fortunately for me, I was doing a little better than the majority of the friends I was drinking beer with. Anyway, a subject was brought up concerning various chat up lines and techniques that each of us were using for pulling women. Many ideas were fielded as to how and what was the best way to attract women. It seemed that there was no definitive answer to the question, as each friend use different techniques in order to meet his goal. The thought came, that there must be a universal strategy that can be applied to getting you 80% of the way to being able to attract women. The other 20% coming from individual techniques and strategies that makes each persons approach appear individual. Various people have called this the 80/20 solution. We came to the conclusion that there were three areas that you should be proficient in each forming one of the corners. Thus we came upon the basis of what we came to call “The Pulling Triangle” the universal strategy that got you 80% of the way there. The final 20% or the icing on the cake came down to learn your craft as a would be Don Juan. Gentleman, I give you the pulling triangle. The first 80%.
In order to understand the simplicity of the pulling triangle we shall break it down into its simplest parts, and discuss each part in detail.
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Get the fireworks back! How to make good sex great
Are you and your partner having good sex — or great sex? Good sex is sex that is generally satisfying and leaves each partner feeling emotionally and physically fulfilled. Great sex is the same, except it is more intense and more uninhibited … the kind of sex you don’t soon forget! Many couples in long-term relationships assume that adventurous and uninhibited sex is a thing of the past. This is particularly true when people get stuck in a “good sex” rut — they go through the same motions every time because it gets the job done. When it is over, each partner has been satisfied … but there certainly weren’t fireworks.
For instance, a couple recently came to see me at the Berman Center seeking help for their love life. Despite their happy marriage, Keith and Elizabeth were experiencing intimacy issues. Sex was infrequent, and when it did occur, it often was dull and monotonous. However, between their full-time jobs and raising three kids, neither of them thought they had time to reignite the passion in the bedroom. In addition to working with them to make space for themselves and each other in their busy lives, I gave Keith and Elizabeth some “homework” to get back in touch with each other’s bodies. I instructed them to engage in a night of VENIS — very erotic no-intercourse sex. In the VENIS program, you can be as imaginative and provocative as you want — massage oils, feathers, body paint, props, etc. The only rule is “no intercourse.” The idea is to enjoy each other’s bodies without rushing toward the finish line. Before sending Keith and Elizabeth off to VENIS land, I supplied them with a basket full of erotic goodies: chocolate body paint, handcuffs, a vibrating rubber ducky and blindfolds. When they came back in for their next session, they told me that their night of VENIS was the best “sex” they ever had! Here are other ways to turn “good” sex into “great” sex: The fantasy box: Create a fantasy box and store it in your bedroom. You and your partner should write down your fantasies on little slips of paper and place them in the fantasy box. Every once in a while, when your sex life needs a little extra oomph, dip into the fantasy box and start playing! Making fantasies come true is a great way to bring spice back into the bedroom.
Tantra: Tantric sex not only prolongs sex and improves the quality of orgasms, it also helps increase the emotional intimacy between you and your partner. One great tantric tool is “soul-gazing.” Here’s how to do it: When you are both undressed, sit on the bed facing each other and place your right hand over your partner’s heart and gaze into your partner’s left eye. Synchronize your breathing while you maintain eye contact. Soul-gazing returns sex to that sacred space where intercourse is a holy, valued activity between two people in love.
Bring “sexyback:” Most women need to feel sexy in order to feel sexual desire. However, between driving in traffic, rushing to make dinner and getting the kids in bed, women often feel harried and unattractive at the end of the day. This is where the importance of “me” time comes in. It may sound cliche, but unless you make time to recharge, nurture yourself and get in touch with your senses (massage, bubble bath, pedicure), it will be hard to feel sexy. You may even invest in a little bit of sexy lingerie. Once you start to feel sexy on the outside, it might change the way you approach intimacy. Who knows? You might even be inspired to give your man a little lap dance. The bottom line is that great sex isn’t as far away as you think. With just a little bit of work, any couple can have fireworks in the bedroom … even on a regular Monday night! Dr. Laura Berman is the director of the Berman Center in Chicago, a specialized healthcare facility dedicated to helping women and couples find fulfilling sex lives and enriched relationships. She is also an assistant clinical professor of OBGYN and psychiatry at the Feinberg School of Medicine at Northwestern University. She has been working as a sex educator, researcher and therapist for 18 years.
Does Sex Make a Difference?
By Linda Bren
National Institutes of Health
If you know how to attract girls, then chasing women won’t be necessary as they will come to you. When a woman is chasing you instead of the other way around, it is much easier to be relaxed and have a good time instead of concentrating on what to do next. So what attracts people, and more specifically girls ? Things that are out of the ordinary. If you blend in with the rest of the world, then no one will ever notice you walking down the street, or in any location for that matter. How do most people blend ? By following what everyone else does and this leads to catastrophic results when trying to attract women. Being a follower is boring and speaks a lot about your personality. It shows that you are insecure to try new things and that you don’t want attention. Now the trick to being noticed is not to dress up in bright yellow colors, but to add one interesting item to your physical appearance. There are a few guidelines to selecting the proper attire that will attract women without making you look like a fool. First steps to being more attractive.
First, take into consideration what kind of social setting you will be in. If you’re going to a club, then you can go all out with outlandish clothing and accessories. However, if you’re going to the library, it would be more effective to carefully choose one single attention drawing accessory. For clubs, keep in mind that you want to look different than everyone else. If everyone else is dressed up with expensive clothing, then wearing something cheap will work better. You’ll automatically be classified as the ‘guy who doesn’t care’, which can be very attractive. If you’re at a place where people are dressed like bums, then feel free to dress up a little more and you’ll automatically be seen as ‘the only classy guy’ in the place. Sometimes clothing itself can make a large enough difference, however accessories can further improve your magnetism throughout the day. Something unique that represents you is the ideal thing. Let’s say you enjoy biking, then you could have a necklace with a bicycle on it for instance. Then, in a social situation, people will notice and comment on your accessories. The more out-of-the-ordinary your accessories are, the more you will get noticed. However, you must be able to continue the conversation and match the boldness of your accessory with your personality. Once you learned how to attract girls, you’ll need to learn how to keep them. The attitude that you have is more important than all the clothes, money and looks in the world. Its cliche, but personality is more important to women than looks. In fact, there are a few secret techniques that will make you irresistible to women regardless of appearance. One of the most effective techniques is called “Cocky / Funny” in the the Double Your Dating book by David Deangelo. It teaches all the fundamental and advanced ways on how to ATTRACT girls and keep them attracted to you permanently.
Easily Attract Girls at Will!
Picture this, you walking down a street and right in front of you, appears a beautiful girl, blonde hair, blue eyes and a body of Venus. As she gets closer to you she looks up, sees you and gives you a fantastic smile. You turn around thinking is it me she is smiling at, and realise that it is. So what you do? As usual you smile back like a grinning fool, do nothing and just walk on by. Sound familiar? Every man that ever walked the earth at some stage in his life has had an experience not dissimilar to this one. It may have been in a bar, on a bus, in the office or workplace or in any other such social situation. Most men ask the question “was she interested in me” the answer to this question is simple! Of course she was you idiot! In sales they would call this a buying signal and you would move in to sign up the deal.
Fear not, understanding the buying-signals of women is only a part of what you will learn in this book. You will learn insights into understanding yourself and how to make yourself the very essence of attractiveness to women. You will learn how to approach and talk to women in a way that will make you both charming and interesting to the fairer sex. You will learn techniques that would give yourself confidence in your ability to attract women at will. You will also understand what women are looking for in men, and like a chameleon mould yourself into that role to achieve your goal. These techniques are both simple to understand, and easy to apply, in fact you should be able to use and apply these techniques from day one. You will become a powerhouse of pulling, the very essence of charm and desirability to women the world over. Your friends will look at you with awe and envy, and wonder where this rich vane or form came from. You will look back with a knowing smile and say, “what can I say I guess I'm just a regular Don Juan”. Just so that you know, all men can use these techniques. From the athlete, to the nerd, from Brad Pitt to the Elephant man, from the very old to those just starting out on their journey into the mysteries of women. These techniques are timeless and transcend all barriers. I often hear said, “There are never any women around that I find attractive” well guess what yes there are half the population of the world are women! By most people's reckoning that is approximately 3,000,000,000 women for you to choose from. So saying that there is a lack of women to choose from is somewhat ridiculous. With all this opportunity that is out there, just waiting for you to make their day, I think we should begin, don't you! The power of the pulling triangle! Pulling is my local colloquialism, for attracting the ladies in a deliberate manner, you may know it by many other names, picking up, chatting up or even sharking. It does not matter what you call it, as it all amounts to the same thing, your effort in trying to find favour with the fairer sex. As the title suggests, there are three sides or points to the pulling triangle. I will talk about them in a little while, firstly I shall tell you how the pulling triangle was developed, it is rather a silly little tale, but there is no denying the power of this technique. The Idea One summer while in the garden of a friend's house, myself and a couple of other friends were sitting around drinking it was a beautiful day the beer was flowing and as with most single guys our thoughts turned to women. Now you need to understand that the guys who were sitting around this particular table were having varying degrees of success with the ladies. Fortunately for me, I was doing a little better than the majority of the friends I was drinking beer with. Anyway, a subject was brought up concerning various chat up lines and techniques that each of us were using for pulling women. Many ideas were fielded as to how and what was the best way to attract women. It seemed that there was no definitive answer to the question, as each friend use different techniques in order to meet his goal. The thought came, that there must be a universal strategy that can be applied to getting you 80% of the way to being able to attract women. The other 20% coming from individual techniques and strategies that makes each persons approach appear individual. Various people have called this the 80/20 solution. We came to the conclusion that there were three areas that you should be proficient in each forming one of the corners. Thus we came upon the basis of what we came to call “The Pulling Triangle” the universal strategy that got you 80% of the way there. The final 20% or the icing on the cake came down to learn your craft as a would be Don Juan. Gentleman, I give you the pulling triangle. The first 80%.
| Looking Good | |
| Felling Good | Talking Good |
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How to make sex on your wedding night unforgettable
There's a general national myth about wedding nights; supposedly, every bride and groom have the most intimate and wonderful sex of their lives on their wedding nights. In reality, while your wedding night may be a little different, it is an intimate moment, and an opportunity. Here are ten tips that can help make your wedding night one of the best evenings of your life.
It's also a good idea to accept the fact that you may be too exhausted or tipsy to have sex. If one of you falls asleep, or isn't in the mood, remember, it's not a prediction of a doomed marriage. Spend the time relaxing and remembering how wonderful your wedding day was. And, if you'll be a virgin on your wedding night, don't forget to read Sex Tips for Virgins on Their Wedding Night
- Take things slowly
Savor this moment. While you may be a little too tired to have the most technically excellent sex of your lives, this is likely to be among your most romantic and intimate sexual experiences.
- Lower your expectations
So this may not be the most amazing sex you've ever had. So what? Try to just enjoy whatever happens.
- Read some sex books
Who couldn't use a little advice from the experts? Some to try: The Good Vibrations Guide to Sex, Sex Tips for Straight Women from a Gay Man and Lesbian Sex Secrets for Men.
- Talk to each other
Spend some time relaxing, talking about the wedding, and about your love for each other. Let things get romantic and sappy. The sex that follows will be intimate and amazing.
- Expand your idea of the "wedding night"
If you're too tired for foreplay, that sex isn't going to be so great. Couldn't it be better to wait until the morning?
- Flirt with each other during the wedding
It can be easy to spend the whole wedding greeting Aunt Sally and Cousin Bob, cutting the cake, and attending to a thousand other details. Don't forget to stop, stare into each other's eyes, share a few extra kisses, and flirt with each other. It will also help build the excitement for your alone time later.
- Don't have sex with each other for a couple of weeks before the wedding
Many couples try this to make the wedding night sex fresh and new again. Others go even further by giving up sex months before the wedding so that they may be virgin-like on the wedding night.
- Try something new
Perhaps there's been something you've been wanting to try? Your wedding night can be a fun night to experiment,
- Wear something special
Wedding night lingerie can really help the mood. Pick something a little different than what you usually wear to excite your partner. Make sure you feel confident in it, as a confident lover is almost always a better lover.
- Set the stage
Help yourselves get into the mood by setting the stage. Light some candles, bring some CDs and a radio, scatter rosepetals, or do whatever helps you get in the mood. And don't be afraid to kick friends and family out early. While they may tease you a little, they'll certainly understand!
It's also a good idea to accept the fact that you may be too exhausted or tipsy to have sex. If one of you falls asleep, or isn't in the mood, remember, it's not a prediction of a doomed marriage. Spend the time relaxing and remembering how wonderful your wedding day was. And, if you'll be a virgin on your wedding night, don't forget to read Sex Tips for Virgins on Their Wedding Night
Get the fireworks back! How to make good sex great
From tantra to toys, Dr. Laura Berman gives ways to reignite
By Dr. Laura Berman
TODAYShow.com contributor
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For instance, a couple recently came to see me at the Berman Center seeking help for their love life. Despite their happy marriage, Keith and Elizabeth were experiencing intimacy issues. Sex was infrequent, and when it did occur, it often was dull and monotonous. However, between their full-time jobs and raising three kids, neither of them thought they had time to reignite the passion in the bedroom. In addition to working with them to make space for themselves and each other in their busy lives, I gave Keith and Elizabeth some “homework” to get back in touch with each other’s bodies. I instructed them to engage in a night of VENIS — very erotic no-intercourse sex. In the VENIS program, you can be as imaginative and provocative as you want — massage oils, feathers, body paint, props, etc. The only rule is “no intercourse.” The idea is to enjoy each other’s bodies without rushing toward the finish line. Before sending Keith and Elizabeth off to VENIS land, I supplied them with a basket full of erotic goodies: chocolate body paint, handcuffs, a vibrating rubber ducky and blindfolds. When they came back in for their next session, they told me that their night of VENIS was the best “sex” they ever had! Here are other ways to turn “good” sex into “great” sex: The fantasy box: Create a fantasy box and store it in your bedroom. You and your partner should write down your fantasies on little slips of paper and place them in the fantasy box. Every once in a while, when your sex life needs a little extra oomph, dip into the fantasy box and start playing! Making fantasies come true is a great way to bring spice back into the bedroom.
Tantra: Tantric sex not only prolongs sex and improves the quality of orgasms, it also helps increase the emotional intimacy between you and your partner. One great tantric tool is “soul-gazing.” Here’s how to do it: When you are both undressed, sit on the bed facing each other and place your right hand over your partner’s heart and gaze into your partner’s left eye. Synchronize your breathing while you maintain eye contact. Soul-gazing returns sex to that sacred space where intercourse is a holy, valued activity between two people in love.
Bring “sexyback:” Most women need to feel sexy in order to feel sexual desire. However, between driving in traffic, rushing to make dinner and getting the kids in bed, women often feel harried and unattractive at the end of the day. This is where the importance of “me” time comes in. It may sound cliche, but unless you make time to recharge, nurture yourself and get in touch with your senses (massage, bubble bath, pedicure), it will be hard to feel sexy. You may even invest in a little bit of sexy lingerie. Once you start to feel sexy on the outside, it might change the way you approach intimacy. Who knows? You might even be inspired to give your man a little lap dance. The bottom line is that great sex isn’t as far away as you think. With just a little bit of work, any couple can have fireworks in the bedroom … even on a regular Monday night! Dr. Laura Berman is the director of the Berman Center in Chicago, a specialized healthcare facility dedicated to helping women and couples find fulfilling sex lives and enriched relationships. She is also an assistant clinical professor of OBGYN and psychiatry at the Feinberg School of Medicine at Northwestern University. She has been working as a sex educator, researcher and therapist for 18 years.
Does Sex Make a Difference?
By Linda Bren
- Gender as a Starting Point
- Drugs and Gender Differences
- Medical Devices and Gender Differences
- Studies of Both Sexes
- Continuing Efforts
Gender as a Starting Point
Men and women are different in every organ of the body--;even their skin, says Marianne J. Legato, M.D., a cardiologist and founder and director of Columbia University's Partnership for Gender-Specific Medicine. They are different at the cellular level, and these differences may influence the amount and type of medicine they need to treat a disease. "Dosage is not adjustable simply on the basis of body size anymore," says Legato. "I think we have to look at a whole variety of factors in prescribing dosages that are safe on the basis of gender." "We know that different people, as individuals, respond to drugs differently," says Miller. "People routinely tell me, ‘Oh, that drug doesn't do a thing for me.'" Some researchers place priority on studying differences in genetic makeup by individual, not gender, says Miller. They want to determine the exact sequence of DNA in a person's body in order to tailor treatments for that individual. "But even if the DNA is the same, men and women will express it differently," says Miller. Researchers looking at DNA sequence may think that's a shortcut, says Legato, "which it obviously would be if we can take a slice of people's DNA and decide whether or not they would react appropriately to any medication to which they've not been previously exposed. That would be the ultimate, but I fear that that's years away. I think it would be nice to know the difference between men and women as a starting point." In 2001, the Institute of Medicine (IOM), part of the National Academy of Sciences, published a report that supported studying potential gender differences during drug development. The IOM concluded that "sex matters"; that is, "being male or female is an important basic human variable that should be considered when designing and analyzing studies in all areas and at all levels of ... health-related research." The IOM defined sex-based differences as biologically based differences in men and women, and described gender-based differences as distinctions shaped by the cultural and social environment. Generally, the FDA does not attempt to determine why men are different from women and refers to any identified difference as a "gender difference."Drugs and Gender Differences
In 1998, the allergy drug Seldane (terfenadine) was removed from the market, when a safer alternative was approved. It had been discovered that Seldane could cause a life-threatening heart rhythm irregularity when used with certain other drugs. More women took Seldane, and more were reported to have had this heart arrhythmia, called torsades de pointes. Researchers at the Georgetown Center for the Study of Sex Differences believe that the male hormone testosterone may protect the heart from some types of arrhythmia, says Verbalis. In addition, he says, research has shown that women are at greater risk for torsades de pointes because of their QT interval--;the time it takes for the heart to relax after it contracts to pump out blood. Women often have a longer QT interval than men, and taking certain drugs can further lengthen this interval, thereby increasing the risk of the fatal arrhythmia more in women than in men. Some drugs are approved to treat a disease based, in part, on patients' reporting of the relief of their symptoms. For example, Zelnorm (tegaserod maleate) is approved only for women to relieve the symptoms of IBS. In clinical trials, more women taking Zelnorm reported relief of their symptoms than those taking an inactive pill (placebo). IBS, which is found more commonly in women, produces a variety of symptoms. "The challenge in the evaluation of a drug for this disease is to determine if there is a gender difference in the patient's perception of symptoms and evaluation of relief of symptoms," says Joyce Korvick, M.D., acting director of the FDA's Division of Gastrointestinal and Coagulation Drug Products. "The perception of ‘relief' of symptoms in men and women may be very different." Because IBS is found more often in women, more women than men were enrolled in the clinical trials for Zelnorm. But for the nearly 300 men with IBS enrolled in the trials, Zelnorm was not shown to be effective. "More research regarding men and women's perceptions of specific disease symptoms is needed to ensure that differences seen in clinical trials are meaningful to the gender being studied," says Korvick. Another drug, Zoloft (sertraline hydrochloride), is approved for both men and women to treat several conditions, including post-traumatic stress disorder (PTSD). This approval was based on clinical trials in which Zoloft showed little effect in men with PTSD, while the drug's benefit over a placebo was clear in the women studied. "True gender differences in responsiveness may have been one explanation," says Thomas Laughren, M.D., team leader for the FDA's psychiatric drug products group. "However, it should also be noted that the types of PTSD differed in the two groups," he says. Many of the men in these trials had a long-lasting and treatment-resistant PTSD, based on military combat experience, compared to many of the women who tended to have a more acute form of PTSD, based on recent physical abuse. Scientists aren't sure why some drugs work better in one gender than in the other. But they do know that differences may occur in the way men and women absorb certain drugs into the bloodstream, distribute them to the body's tissues, break them down, and rid them from the body. The way the body handles a drug is known as pharmacokinetics (PK), and was the subject of an FDA study. FDA researchers examined 300 drug applications submitted to the agency between 1994 and 2000. More than half of these applications contained information on the effect of gender on PK. The PK was the same for 80 percent of the drugs in which PK was studied. But for the other 20 percent of the drugs, the PK was different. "There must be some reason for this difference," says Miller. "That's where research comes in. We want to understand the biology and the mechanism enough to predict what's going to be in the 80 percent group and the 20 percent group. Then we can predict how a product's safety or effectiveness will be influenced in each gender." Shiew-Mei Huang, Ph.D., deputy director for science in the FDA's Office of Clinical Pharmacology and Biopharmaceutics, says that drug metabolism plays an important role in the way men and women respond to drugs. An enzyme known as cytochrome CYP3A helps metabolize many drugs, and studies have shown that women have more cytochrome CYP3A in the liver, says Huang. Some drugs or dietary supplements, for example, St. John's wort, increase the activity of this enzyme, which makes the drugs break down faster. This rapid breakdown reduces the amount of the drug in the body, decreasing its effectiveness in women. The reverse scenario may also occur: A drug could slow down enzyme activity, causing too much of the drug to build up in the body and resulting in more side effects. But biology can't explain all the differences in the way men and women respond to drugs, cautions Huang. Other factors, such as medication use, must be considered. "A recent survey showed that women, in all age groups, tend to take more medications, including dietary supplements, than men," says Huang. This difference may put women at more risk for certain drug interactions than men.Medical Devices and Gender Differences
Men and women may also respond differently to certain medical devices and the procedures in which they are used. Several FDA studies have focused on identifying some of these differences. In 2003 and 2004, FDA researchers studied more than 150,000 people with suspected heart disease and found that women had about twice the risk of men for local complications after cardiac catheterization. In the catheterization procedure, a slender tube is inserted into a large artery in the leg (femoral artery) and is threaded up through the body to the heart to diagnose or treat narrowed heart arteries that block blood flow. "The study was done to look at risks associated with hemostasis devices," says Dale Tavris, M.D., M.P.H., an FDA epidemiologist specializing in preventive medicine. These devices are used after cardiac catheterization to prevent continued bleeding of the femoral artery where the catheter is inserted. We don't know why complications, such as hemorrhaging, occurred more in women, says Tavris. "There's speculation that it may be due to blood vessel size or hormonal differences. And the risk applies whether or not the hemostasis devices are used." Further information is needed to understand these occurrences, says Tavris, before we can determine whether any changes to the catheterization procedure or to hemostasis devices or their labeling are appropriate. An FDA-sponsored study at Boston University involves men and women with diabetes who are using blood glucose monitors at home to test their blood several times a day. Researchers are looking for any differences in testing blood drawn from the fingertip or from another part of the body, since newer glucose monitors use blood samples from alternate body areas. "We found that the fingertip can have a different glucose value from an arm or leg, especially when sugar levels are changing rapidly, for example, after a meal or after exercise," says Jean Cooper, D.V.M., director of the Division of Chemistry and Toxicology in the FDA's Center for Devices and Radiological Health. The study is continuing to determine whether gender might be a factor in this difference in glucose values. The FDA now requires glucose monitors to carry a warning label cautioning against using alternate sites when glucose levels are changing rapidly. If a manufacturer can show in clinical trials that its device doesn't demonstrate this variance, the warning is not required.Studies of Both Sexes
In 1977, an FDA guidance said that women able to become pregnant should not participate in the early phases of drug studies, with an exception for studies of potentially life-saving drugs. The exclusion reflected the concern that if a woman became pregnant, the baby might have birth defects. Over more than two decades, the FDA has worked to ensure that both women and men are represented fairly in clinical trials involving drugs, biologics such as vaccines and blood products, and medical devices. In 1988, the agency issued guidance to drug makers asking that the safety and effectiveness data in drug applications be analyzed according to gender, age, and race. And, in 1993, the agency issued its Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs, known as the gender guideline. When the gender guideline was published, the FDA also revoked the 1977 restriction on women of childbearing age in early drug studies and reiterated the need to include patients of both sexes in the development of drugs, biologics, and medical devices. The guideline also recommended that drug companies analyze separately men's and women's responses to drugs. Attention to potential gender differences became part of a larger agency effort to ensure that the safety and effectiveness of drugs are adequately studied in people who represent the full range of patients who could use the drugs when approved. In a 1998 regulation known as the Demographic Rule, the FDA again addressed the importance of collecting data on clinical trial volunteers by gender, race, and age. The regulation required companies to analyze the data to look for possible differences in effectiveness, safety, and dose-response and to submit this information in applications for new drugs. It also required reporting demographic data in annual reports during a drug's investigation phase. A regulation in 1999 gave the agency the authority to halt studies of new drugs to treat life-threatening diseases if clinical trials excluded women solely because they could become pregnant. "The Demographic Rule and gender guideline represent our commitment to looking at possible differences in various subgroups' response to drugs, whether men and women, black and white, old and young," says Robert Temple, M.D., director of the FDA's Office of Medical Policy. "The guidance tells drug sponsors what our expectation is and what we're looking for." So far, a small number of differences have been found in the way men and women respond to drugs, says Temple. An FDA study reviewed gender-related labeling for 171 new drugs that were approved for both males and females from 1995 through 1999. Labeling for two-thirds of the drugs contained some statement about gender, although only 22 percent described actual gender differences and none of these differences were considered significant enough to recommend any change in dosage for one gender. "But just knowing that is useful information," says Miller. "You know you can take these drugs without a higher risk because of your gender." The FDA is also working to revise drug labeling so that both consumers and health care providers can better understand important information about a drug. A proposed FDA rule will require prescription drug labels to contain "highlights" in a prominent place. The highlights will discuss the more serious and common side effects and significant gender differences found in clinical trials.Continuing Efforts
The FDA's Office of Women's Health is funding research within the agency to examine gender differences--;particularly in the areas of heart disease, obesity, and HIV--;that are important for the agency to consider in regulating medical products. In one project funded by the OWH, scientists within the FDA's Center for Biologics Evaluation and Research are studying the replication of HIV, the virus that causes AIDS, in human blood cells from male and female blood donors. By infecting the blood cells with HIV in a culture medium and then adding various sex hormones, scientists are learning more about the influence of gender on the concentration of the virus. They are also studying the effect of sex hormones on certain antiviral drugs used to treat HIV. "Some of the things we're looking at may affect when treatment should be started in men and women," says Andrew Dayton, M.D., Ph.D., an FDA research medical officer. And it may give us preliminary insight into how gender might affect response to HIV treatments, he adds. This information may help in designing clinical trials to test the effectiveness of HIV treatments in men and women. In another initiative, the OWH is developing an innovative knowledge management approach to make better assessments in groups of people (subpopulations) to protect patient safety. The Demographic Information and Data Repository (DIDR) was mandated by Congress in 2002 to monitor the inclusion of women in clinical trials and to study gender differences and variability in response to medical products. Katherine Hollinger, D.V.M., M.P.H., a senior health promotions officer in the OWH, says the DIDR will help the agency to look at groups of people--;including groups characterized by gender, race and ethnicity, older people, and children--;in a more informed way. "It will allow us to better look at subpopulation issues and differences in drug response that may affect safety and effectiveness," says Hollinger. "And it will allow us to not only track inclusion of women and other populations in clinical trials, but to monitor the types of trials women, children, or the elderly are participating in and identify patterns that are observed." Other benefits of the agency-wide DIDR include helping the agency to design better studies for new products, enabling more efficient and informed reviews and approval decisions, and allowing better assessments of product labeling. Part of the problem in looking at study data to determine subpopulation differences in response to medical products is the lack of standard approaches and terminology used in individual studies. The agency is working with the pharmaceutical industry and standards organizations to establish standardized approaches to labeling, study data, and study protocols that will be used in the DIDR to protect the safety of women, men, children, and older people of every race and ethnicity.Men, Women, and Disease Risk
| Heart attack | Men have more, but women are more likely to die within a year after a heart attack; women tend to get heart disease seven to 10 years later than men |
| Stroke | Women have fewer strokes, but are more likely to die from them than men; women are generally older than men when they have a stroke |
| Depression | Twice as common in women |
| Migraine | Three times more common in women |
| Hearing loss | More common in men |
| Nearsightedness (myopia) | More common in women through age 60 |
| Irritable bowel syndrome | More common in women |
| Cancer | Cancer of the lungs, kidneys, bladder, and pancreas are more common in men; thyroid cancer is more common in women |
| Osteoporosis | More common in women |
| Rheumatoid arthritis | Two to three times more common in women |
| Gout | More common in men |
| Lupus | Nine times more common in women |
| Fibromyalgia | Nine times more common in women |
Men, Women, and Heart Disease
Heart disease is the leading cause of death in the United States for both men and women, according to the American Heart Association. "But the normal heart is different in men and women," says Marianne J. Legato, M.D., a cardiologist and founder and director of Columbia University's Partnership for Gender-Specific Medicine. "Women's hearts beat faster, even during sleep," she says. And women have different proteins in the heart cells. "Some data suggest that the whole physiology of the coronary arteries and what keeps them open and what causes them to go into spasm might be significantly different in men and women," says Legato, adding that some women have had heart attacks without any of the fatty buildup of plaque seen in the coronary arteries in most people with heart attacks. And the symptoms of a heart attack may be different. "Twenty percent of women will not have the ‘typical symptoms' of chest pain radiating down the left arm," says Legato, "but will instead describe nausea, profound sweating, and shortness of breath and pain in the upper abdomen."
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