Archive for the ‘personalized medicine’ Category

Much in women’s health revolves around folliculogenesis – from teen age to peri-menopause

November 30, 2011

In this article I sketch for you the usefulness of the Ovulona™ Smart Sensor™ throughout a woman’s life, with particular attention paid to the extremes of the reproductive lifespan.

We outline the significance of the cervical tissue biosensor for a woman’s health management from adolescence (the teen years) to peri-menopause. This schematic diagram is a pictorial synopsis of the multi-purpose utility of the Ovulona throughout most of a woman’s lifetime.

Ovulona throughout a woman's life

As you recall from prior posts on this blog, FIV™ stands for FOLLICULOGENESIS IN VIVO™, which translates as the sequence of menstrual cyclic records that will be captured and stored (automatically saved) in the Ovulona during normal use by a woman at home. The data is available for transfer to healthcare providers’ Ovulograph™ for medical uses during the reproductive years.

The reproductive age is officially defined as 14 to 44 but we’d encourage, for health reasons, to chop off a few years at both ends from the actual reproductive (high end) or sex-exploration activities (low end). When folliculogenesis – i.e. menstrual cycling – ceases in menopause, hormone therapy and cervical tissue health screening are the two components of menopause and post-menopause health management, to which the Ovulona is applicable.

In this article, I address very briefly (tweetingly!) the two “boundary conditions” of said reproductive years.

I’ll deal with the young boundary condition, i.e. adolescence or teen age, in the style popular nowadays especially at that stage of life . That is, I let speak a few tweets, mostly from http://topsy.com/biozhena.wordpress.com/2009/03/12/far-more-than-a-tool-for-reproductive-management/ .

When you look at the tweetingly referenced papers (click the short URLs below), you will see how the teen cramp sufferer needs our Ovulona. That’s because she must take the anti-inflammatory medication before the ovulation-linked pain hits, otherwise the med would not work. She – or is it you? – must be able to anticipate ovulation. You need the Ovulona. The timing is crucial, similar to the right timing for conception purposes… (Recommended reading: http://endometriosis.org/treatments/painkillers/ = http://to.ly/6ZsS in the #NSAIDs tweet below).

If it’s menstrual bleeding (not ovulation) that pains you, the Ovulona will tell you when you expect that – whether it is ovulation + 14 days or, probably more likely at this young age, ovulation + irregular. You’ll then see on the display your recorded min and max, with respective probabilities the more accurate the longer you’ve used the Ovulona. That’s this app’s meaning of Smart Sensor™ for you! (And that is because we don’t track just this or that hormone in your pee! Or your BBT, or your signs…)

As for the STD screening aspect of those young years, indicated in the pictorial synopsis above, I refer you to the recent posts in this blog; and the sex ed use of the Ovulona – or rather its recorded data and their discussions in classes – is self-explanatory.

But then there is the subject of chemical contraception, the Pill. So, here, a couple of tweets from http://topsy.com/biozhena.wordpress.com/2010/06/27/about-atrophy-reproductive-aging-and-how-it’s-really-not-nice-to-fool-mother-nature–or-with/?utm_source=topsy_module

A teenage girl has a #dilemma With the #Pill she brings on herself a significantly earlier #menopause & likely difficulty to #conceive when desired http://to.ly/5f2W

#Menstrual #cramps are bad but don’t allow them – by taking the #Pill – to cause you the much worse #pain of TTC #infertility http://to.ly/5f2W    [TTC = Trying To Conceive. That’s the phrase and acronym used by people who have difficulty getting pregnant.]

http://to.ly/5f2W Even with just 3-15 months of #contraceptive #pill use you suffer greater loss of S crypt cells than can be replaced. Then hard TTC is likely   [S crypts are part of the microscopic structure of the cervical epithelium, of the tissues.]

Here now are those few tweets referring to dysmenorrhea, the menstrual pain which causes so much suffering and so many lost hours at school and/or at work. In this day and age!

#NSAIDs against #endometriosis pain http://to.ly/6ZsS Since you must take the meds BEFORE expected #cramps you need our Ovulona tool to anticipate ovulation http://to.ly/MJS [NSAIDs = Non-Steroidal Anti-Inflammatory Drugs]

@bioZhena/fertility    http://to.ly/MJS Why most girls get cramps What goes on there Why & what’s PCOS See it with Ovulona [Obese girls tend to grow into women with PCOS = Poly Cystic Ovary Syndrome, the cause of major killer diseases, and often causing infertility.]

Folliculogenesis #InVivo for Why Do Most Girls Suffer With #dysmenorrhea #cramps http://to.ly/MJS #womenshealth #diagnostic #medicaldevice

Ovulona for etiology & management of  #dysmenorrhea Why do teen girls suffer with #crampshttp://to.ly/MJS #pharma #medtech #medicaldevice [etiology = the cause or origin of a disease]

Re: etiology of adolescent #dysmenorrhea Prostaglandin theory & treatment known since the 1980s Why are period cramps still so bad?

I leave you and this “boundary condition for Ovulona’s use” with two Google Insights graphs. Look here how the worldwide interest level in the subject of period cramps has been increasing since 2004.

Period cramps worldwide searches from 2004 by Google Insights

Period cramps worldwide searches from 2004 by Google Insights

Don’t ask me why the recorded public interest is emanating from those particular English-speaking countries and not from numerous others, and look for details at http://www.google.com/insights/search/#cat=0-45&q=period%20cramps&cmpt=q (you can change the selected parameters and observe the effect of the changes).

I merely note the periodicity developing in the data in recent years on top of the clear upward trend, the periodicity indicative of highest interest in summertime (such as in July 2011)…

This is, of course, the same in the next graph, where I added dysmenorrhea (red) for comparison. That’s a difficult word, so it is not as much searched on as the colloquial cramps – except for, if you look closely, in (Southeast)Asia.

Period cramps & dysmenorrhea worldwide searches since 2004 by Google Insights

I’ll now use one more tweet to segue into the other end of the span of reproductive years.

#estrogen can be a good medication but we need #personalizedmedicine tools We must measure & titrate #hormone uptake http://t.co/CeCsWgn

The following illustration shows that we at bioZhena have the technology with which to do that, i.e. a tool with which to adjust treatment to suit a given female patient.

The illustration is a graph of the effects of estrogen and progesterone monitored with our technology in an ovariectomized pig. Ovariectomy is the removal of the ovaries. It is the animal equivalent of surgical hysterectomy, which causes surgical menopause since the reproductive system no longer produces said sex hormones, the sex steroids estrogen and progesterone.

In the illustrated experiment, the steroids were later given to the animal (after recovery from surgery), and the result was that progesterone drove the sensor signal down versus estrogen drove it up (as seen in FIG. 5 below, excerpted from our patent portfolio). This is a useful finding, for example for monitoring the effects of hormone replacement therapy (HRT). 

Graph of estrogen and progestagen effects on porcine cervix

Graph of estrogen and progestagen effects on porcine cervix

We also have the proof of the concept generated by a menopausal woman, using a Premarin treatment in that experiment (Premarin is an estrogen medication used for treating the symptoms of menopause including hot flashes, vaginal dryness, etc.). The data was used in another patent in our portfolio.

Background on menopause, HRT and bioZhena can be found in the early blog post at https://biozhena.wordpress.com/2007/12/18/menopause-hrt-and-biozhena/ .

Experts advocate that women in their 30s and 40s should look at menopause now. Health maintenance depends on diagnostic tools. We propose that the preparation for menopause be done – in a simple quick daily routine – by systematically monitoring the Ovulona menstrual cyclic profile, and how it changes over the years. How it responds to pregnancy and birth, to things like diet, exercise, various ills, various medications, stress… in the particular woman user, not some statistical average. For evidence-based personalized health care.

That’s the broader meaning and the purpose of the folliculogenesis cyclic profile generated by the Ovulona. It’s not merely (“merely”!) for helping to get pregnant or for avoiding pregnancy without chemicals, as is illustrated and described in “Pregnancy and birth control how-to by bioZhena” at this Photobucket site. In the third graphic, on this page, see the follicular waves that relate to follicular age, i.e. how fast is menopause approaching, after pregnancies were successfully achieved and then regulated in this Ovulona-guided manner.

This is because the cervix monitors the physiological inputs after conception and after pregnancy just like it does the monitoring before fertilization and before birth. We pick up the diagnostically useful information from this key female organ. We speak of end organ effects.

For a still broader perspective, including symptometric monitoring correlated with folliculogenesis, go to “Far more than a tool for reproductive management”.

STOP PRESS

And after all that, go and check out the 2012 post “The fallacy of ovulation calculators, calendars and circulating-hormone detectors” at https://biozhena.wordpress.com/2012/02/13/the-fallacy-of-ovulation-calculators-calendars-and-circulating-hormone-detectors/

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Why screen for cervical cancer (and for the other STIs, sexually transmitted infections)?

July 29, 2011

Why all women need to screen for cervical tissue health, whether or not they accept that Nature is powerful (only  virgins don’t need to)

I will tell you why screening for this sexually transmitted infection (STI) is much needed, if you promise that you will not shoot the messenger. Exaggerating? Not really, if or when you realize that chances are that you yourself are already infected.

Is it so serious?

I say that because “current evidence suggests that at least 50 percent of sexually active women have been infected with one or more types of HPV”. Most people with HPV have no symptoms. When the infection is present, symptoms may or may not include genital warts.

HPV stands for Human Papilloma Virus. That is the virus that causes cervical cancer, and goes slowly about it, which is both good and bad. Good because the disease can be treated before it kills, and bad because it may take so long before it raises its ugly head that it can come completely unexpected in the mature middle age and even later. That is why vigilance (meaning, screening for it) throughout one’s lifetime is well worth it – unless you are a fatalist.

Collage of drevoryt woodcuts Dekameron, Ceský dekameron, Bakchanálie by Zdenek Mézl 1980

Collage of drevoryt woodcuts Dekameron, Ceský dekameron, Bakchanálie by Zdenek Mézl 1980     Links:      http://www.ikup.cz/item.php?id=600279&lan=EN        http://www.galerieart.cz/mezl_cesky_dekameron_I.JPG              http://www.galerieart.cz/prodej_mezl_staroveke_baje.htm

“Furthermore, the potential risk of infection from non-penetrative sexual contact remains undetermined, including the possible association between oral-penile contact and oral HPV, which is associated with oral cancer.” You can read this online in the peer-reviewed scientific publication Am. J. Epidemiol. (2003) 157(3): 218226. The experts give a reference (ref. 3) for the 50%+ statistic, and elsewhere the Medical Institute for Sexual Health writes http://www.medinstitute.org/public/92.cfm  : “About half of all sexually active 18- to 22-year-old women are infected with it (ref. 10 = J Infect Dis. 2001;183(11):1554-1564)”.

Either way, let’s watch out for the killer disease, which fortunately is curable – if caught early. If not caught early (that is, if not detected, diagnosed and treated), The Ravisher wins.

Cervical cancer causes about the same number of deaths as HIV/AIDS every year [two references for this statement are cited in the above Medical Institute article http://www.medinstitute.org/public/92.cfm ].

Young Woman Attacked By Death (or The Ravisher) - Albrecht Durer

Young Woman Attacked By Death (or The Ravisher) – Albrecht Durer

Get this! The most common STI. Both young and mature women in danger

Get this: The human papilloma virus (HPV) is the most common sexually transmitted infection (STI) in the world, and it is the most important cause of cervical cancer, a major killer of women worldwide (the second biggest).

Another horrible statistic is that, according to a CDC study, one in four (26 percent) young women, girls between the ages of 14 and 19 in the United States – or 3.2 million teenage girls – are now infected with at least one of the most common sexually transmitted diseases. Those are human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. See http://www.sciencedaily.com/releases/2008/03/080312084645.htm .

A bad news for the mature women, who are past their best years for birthing, is this: “Cervical cancer is the second leading cause of cancer deaths among women worldwide. Human papillomavirus (HPV) has been shown to be the precursor of cervical cancer in over 99% of the cases. … Although women aged 40 and above are not specifically considered high risk for HPV infection, many women are testing positive in this age group and are facing the impact of an HPV diagnosis that implicates a sexually transmitted disease and is known to be a precursor to cervical cancer.” So is written in J Am Acad Nurse Pract. 2010 Feb; 22(2):92-100, in a paper titled “The human papillomavirus in women over 40: implications for practice and recommendations for screening”.

The Plague by Arnold Böcklin, 1898

Arnold Böcklin, The Plague, 1898

Pap smear test. Important. But problematic

While the Pap smear diagnostic screening has significantly improved the situation over the many years since its introduction (first published by the inventor, Dr. Georgios Nicholas Papanikolaou late in the decade of “the swinging 1920s” but only recognized in the 1940s), at least 12,000 women are diagnosed with cervical cancer each year in the United States, accounting for at least 4,000 deaths. Statistics cited from J Sch Nurs. 2007 Dec; 23(6):310-4.

As commented in June 2011 at http://to.ly/aCD3 (http://www.telegraph.co.uk/news/health/news/8554793/Women-making-excuses-to-avoid-cervical-cancer-smear-tests.html ), #Cervical #cancer “smear tests are invasive, uncomfortable, embarrassing, and often are badly diagnosed”. Another reader concluded: “De-stigmatize cervical  cancer and do some work to make the test less unpleasant – more #women will go” (will go to get the expensive test at a clinic, hoping for a negative result – and for not getting an unexpected huge bill, whether insured or uninsured in the U.S.).

Additional to the advantage of an objective electronic test over the subjective evaluation of a Pap smear: Is there a better way to avoid stigmatization than testing for cervical health in the privacy of one’s home, and in so doing making the test incomparably less off-putting, painless and perfectly affordable for anyone?

Similar to what the Pap smear can do, our tissue biosensing technique should detect the pre-cancerous tissue aberration called squamous intraepithelial lesion (SIL) or dysplasia, which is the earliest form of pre-cancerous lesion recognizable by a pathologist. Refer to http://en.wikipedia.org/wiki/Carcinoma_in_situ .

Unlike the pathologist’s subjective assessment of the Pap smear sample, our in vivo monitoring method provides for an objective electronic evaluation.

In countries like India, the cervical cancer prevalence statistics are much worse, an order of magnitude higher. A big problem is that, among the general population, “knowledge about the relationship of HPV to cervical cancer is low even in the United States and the United Kingdom”. [Rapose A., Human papillomavirus and genital cancer. Indian J Dermatol Venereol Leprol 2009;75:236-44.] So therefore, we are trying to do something about that.

Screening is really necessary. Here is why

There are two main reasons why screening for cervical cancer is and will continue to be necessary.

1. One is that the recently introduced HPV vaccines are far from perfect, and they explicitly require continued screening. Even the most expert proponents of HPV vaccination, and not just the vaccine manufacturers, say and write that.

Antonín Procházka, Milenci s knihou, litografie/lithograph, 1941

Antonín Procházka, Milenci s knihou, litografie/lithograph, 1941

2. Then there is the other reason for the necessity of continued cervical cancer vigilance. It is that, contrary to the oft trumpeted exclamations, the classic “invention of a certain doctor Condom” does not make for safe sex, because it (the condom) only reduces, and certainly does not eliminate, not only the chances of becoming pregnant but also the chances of contracting a sexually transmitted infection. These are medico-scientifically proven facts.

The condom and similar barriers do not completely and reliably eliminate the chances of pregnancy if you happen to have sex during the mere three fertile days of your menstrual cycle (when you are outside of the fertile window, pregnancy simply cannot occur). And, condoms and similar barriers do not completely eliminate – they only reduce – the chances of contracting sexually transmitted infections including HPV.

Sources, evidence – cervix is vulnerable

For sources of this statement of fact, see for example the already referenced http://www.medinstitute.org/public/92.cfm : “Each year, there are about 19 million new infections; half of these are in people under 25 (ref. 2). Many of these STIs have no cure. Untreated STIs can cause infertility, cancer and even death.” In that article is also where you see the references for the statements that “If you use condoms every time you have vaginal sex, you can cut your chance of getting HPV by up to half (references 6,7,8,9)… In women, cervical cancer causes about the same number of deaths as HIV/AIDS every year (refs. 12,13).”

Note this: Evidence shows that HPV is contracted if sex is had at too early an age and/or if sex is had promiscuously as a one night stand entertainment, or even too early into a relationship.

The cervix is particularly vulnerable to infection between the first menstruation and the age of sixteen because there are still many undifferentiated cells at the surface of the cervix, which is therefore  susceptible to HPV infection [http://www.mendeley.com/research/early-first-intercourse-risk-factor-cervical-cancer/]. As cancer is a disease of failure of regulation of tissue growth, HPV causes these cells to transform into cancer cells by altering the genes which regulate cell growth and differentiation.

Edgar Degas - Young Spartans Exercising, circa 1860

Edgar Degas – Young Spartans Exercising, circa 1860

An interesting story associated with the Degas painting includes “that the work could encompass a variety of meanings”, and that the fully dressed onlookers in the background are the youths’ mothers with Lycurgus, the legendary lawgiver of Sparta, who established the military-oriented reformation of Spartan society in accordance with the Oracle of Apollo at Delphi.

Reflecting on research findings

This blog post is not some exercise in moralizing. I am merely reporting or reflecting on medico-scientific findings. The above-referenced epidemiologists, Winer et al. [Am J Epidemiol 2003;157:218-26], evaluated young college women in Washington State and found that the risk factors for acquiring a new HPV infection included:

  • sex with a new person in the previous 5-8 months,
  • smoking, and
  • use of oral contraceptives.
  • Always using condoms did not provide protection according to this study.

The experts concluded that “in this population of female university students, the risk of infection associated with new partner acquisition is independent of prior sexual experience”, and that a “…finding suggests that an increased risk of incident HPV infection is more strongly associated with sex with a new partner than with sex with ongoing partners.” Thus written.

Peter Paul Rubens - The Union of Earth and Water, c. 1618

Peter Paul Rubens – The Union of Earth and Water, c. 1618                                  For the sake of appropriate symbolism, her name should be Aphrodite or Venus, of course, the promiscuous  goddess of love, beauty and sexuality!

The authors wrote (and here we cite selected notions to reinforce the mentioned ones).

QUOTE:

  • We detected a significant association between current smoking and incident HPV infection…
  • We also observed a significant association between current oral contraceptive use and incident HPV infection.
  • Having known a new partner for less than 8 months before vaginal intercourse was associated with an increased risk of HPV infection.
  • Reporting a new sex partner who has had one or more or an unknown number of prior female sex partners was also a significant predictor of incident HPV infection.
  • [Data] seems to suggest that the better and longer a woman knows her partner before intercourse, the less her risk of becoming infected with HPV.
  • Consistent with previous studies (4, 7, 11, 17, 29, 30), we observed no protective effect associated with condom use. … Since HPV is transmitted presumably through skin-to-skin contact, condoms may not protect against HPV because the virus can be transmitted through non-penetrative sexual contact.
  • Although vaginal intercourse is clearly the predominant mode of genital HPV transmission … any type of non-penetrative sexual contact was associated with an increased risk of HPV infection in virgins.
  • At 24 months, the cumulative incidence of first-time infection was 32.3%… [FYI: That’s 32% of the 603 young women studied between September 1990 and September 1997 by interview and a standardized pelvic examination every 4 months, including HPV DNA analysis from separate cervical and vulvovaginal swab specimens.]
  • Smoking, oral contraceptive use, and report of a new male sex partner –in particular, one known for less than 8 months before sex occurred or one reporting other partners– were predictive of incident infection. Always using male condoms with a new partner was not protective.
  • The data show that the incidence of HPV associated with acquisition of a new sex partner is high and that non-penetrative sexual contact is a plausible route of transmission in virgins.
  • HPV infections are highly prevalent, and current evidence suggests that at least 50 percent of sexually active women have been infected with one or more types (3).

In conclusion, the present study showed that the incidence of genital HPV associated with acquisition of a new sex partner is high, and that risk of infection is especially high if a partner has been known for less than 8 months and if a partner reports having had sex with other partners.

END OF QUOTES

[from Winer et al., that’s Rachel L. Winer, Shu-Kuang Lee, James P. Hughes, Diane E. Adam, Nancy B. Kiviat and Laura A. Koutsky, in Am J Epidemiol 2003;157:218-26, “Genital Human Papillomavirus Infection: Incidence and Risk Factors in a Cohort of Female University Students”. Let’s also reference http://www.google.com/search?q=Koutsky+LA%2C+Kiviat+NB.+Human+papillomavirus+infections.+In%3A+Holmes+KK%2C+Mardh+PA%2C+Sparling+PF%2C+et+al%2C+eds.+Sexually+transmitted+diseases.+3rd+ed.+New+York%2C+NY%3A+McGraw-Hill%2C+1999%3A347%E2%80%9360.+&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a].

Conclusion: Nature is powerful. Nature regulates

My conclusion for you is no preaching but an observation that all this is because Nature is powerful. As simple as that.

In terms of a clarification, or rather a rationalization of the reported findings, since you have an inkling about tissue rejection problems in organ transplantation (you’ve heard about that, haven’t you), I can draw a parallel for you. Think of the meeting of the male and female flesh as a short-lived tissue implant. If the two tissues don’t know each other, if the female has not known the male for sufficiently long, there is a natural reaction, which the cited experts have found manifested as HPV infection (a hint at how that happens: a stranger’s DNA attacks the recipient).

And what’s all this about that Nature is powerful? Well, it is simply to keep in mind that there are some natural laws and principles, such as the one about action and reaction. And, it’s about that Nature regulates

So, there will be a reaction to too much of a good thing (or a bad thing, any thing). I don’t want to get into this too much except to recall that, since the sexual revolution of the 1960s, there has been an enormous increase in the incidence of sexually transmitted infections. Had Georgios (“Pap”) not invented his test in “the swinging ‘20s”, someone would have had to do it in the “revolutionary ‘60s”

As it was, Mrs. Sanger had persuaded her wealthy-widow investor friend that this particular “magic bullet”, her idea of a “magic pill”, was the right approach to reproductive management. Thanks to the Pap, the Western world was sort of ready for the consequences of the Pill at least in terms of the ensuing epidemic of STDs, if not of the epidemic of infertility and of other as yet poorly recognized consequences of this fooling with Mother Nature (à la Ms. Sanger and Mrs. McCormick – “as easy to take as an aspirin”).

The fact is that “while an estimated 1 in 4 Americans will get an STD (sexually transmitted disease) in their lifetime,4 … the United States continues to have the highest STD rates of any country in the industrialized world.2 No effective national program for STD prevention exists… and the American public remains generally unaware of the risk for STDs and the importance of prevention and screening” (per the Kaiser Family Foundation and American Social Health Association).

The National Cervical Cancer Coalition writes:

“By age 24, at least one in three sexually active people are estimated to have had an STD. Teenage girls are especially vulnerable to contracting gonorrhea and chlamydia, which can more easily infect the immature cervix.”

Perhaps you have gathered, from the various bioZhena’s Weblog articles and from our other web information, that we propose to do something about it – about making possible private screening at home for early warning devoid of the problems associated with the Pap smear test.

Oskar Kokoschka, Rejected lover, 1966

Oskar Kokoschka, Rejected lover, 1966

Originally, I intended to illustrate these concluding thoughts with a painting by the grandson of Sigmund Freud, Lucian or Lucien, who passed away the other day (a painting of a sad woman’s face showing from under a bed cover, with a clothed man – guess who – standing hands in pockets and just staring at her – it’s #5 in http://pul.se/muse_Cleveland-Cleveland-OH-caroline-blackwood-2LYALDu533r,d5oww4DQguiE).

But then, Oskar’s more colorful impressionist image seems, well, more colorful, and less realistic… as paintings go.


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