Posts Tagged ‘Odeblad’

Difficult to conceive – Google evidence that pregnancy complications and trying-to-conceive concerns shot up after the Pill launch in 1960s

December 18, 2011

Regardless of what contraceptive proponents tell you

On this day when Vaclav Havel passed away. In this post, I come out explicitly with an argument against the use of contraceptive pills and related agents (all Endocrine-Active Compounds [EACs]), because of the serious consequences of the sex steroid chemicals for women’s health. I start with evidence from Google statistics.

It is possible to examine the English-language literature for the frequency of addressing certain topics over a period of time. I already did this in the recent post “Seven billion people – after half a century with the Pill”.

Let’s look at data from Google Ngram Viewer about the statistics of the occurrence of certain topics (such as difficult birth) in all books published in English. The data is obtained via http://books.google.com/ngrams/info – for anyone to examine.

Briefly, when we enter phrases into the Google Books Ngram Viewer, it displays a graph showing how frequently those phrases occurred in a corpus of books (here English-language books) over the selected years (here 1900 to 2000). The data is normalized by the number of all books published in each year.

Here we have a comparison of statistics of three phrases:

pregnancy complications (blue),

difficult birth (red), and

trying to conceive (green).

Ngram 6: pregnancy complications, difficult birth, trying to conceive

Ngram 6: pregnancy complications, difficult birth, trying to conceive

The topic of difficult birth exhibits an almost linear growth over the century, even though there are discernible steps in the early years such as the step that followed the plateau (flat portion) lasting from about 1915 to just before 1930, when it “shoots up to catch up with” the overall trend. And, overall, the red curve grows steadily from 1900 to 2000.

In contrast, the blue curve of pregnancy complications and the green curve of trying-to-conceive both shoot up only after 1960, the decade of the introduction of the contraceptive pill. The steep rise in pregnancy complications books (blue) starts soon after 1960. The rise in the number of books about trying-to-conceive (green) starts in mid-1970s and is also distinctly faster than the steady growth over the century of books on difficult birth (red), although it is slower than the pregnancy complications that started going up some ten years earlier.

Of course, the green trying-to-conceive curve is not uninteresting in the early decades of the century, either, if only because it appears that the late Victorians had a significant interest in the topic, much higher than in the other two and especially as compared to pregnancy complications (blue). I’ll leave any discussion of the trend there to others, although the downward trend in the first half of the century would seem consistent with the rise of the birth control movement and with the consequences of two World Wars, and the Great Depression in between.

Peter Paul Rubens, Allegory of War, c. 1628

Peter Paul Rubens, Allegory of War, c. 1628

Those two generations had it tough but, on the other hand, their health, the health of humankind, was not yet assaulted by the sex-steroid chemicals that were introduced in the 1960s.

In a previous bioZhena’s Weblog post, you can see evidence that oral contraceptive use directly and negatively impacts the cervical crypts, which brings about the difficulty to conceive. The bottom line is this: “After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced.” The S crypts are needed for conception.

To further cite Professor Erik Odeblad: “Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced. Treatment is difficult.”

This is a serious problem because, according to medical literature, most American women, “approximately 85% of U.S. women will use the OC (oral contraception) for an average of five years.1 However, women’s OC use, similar to other chronic medications, is often inconsistent and transient.2 Reported six-month OC discontinuation rates vary from 18% to 50%.3,4,5 Unintended pregnancy often follows OC discontinuation” END OF QUOTE. (Am J Obstet Gynecol. 2007 April; 196(4): 412.e1–412.e7)

These data can be read and understood as the double-whammy put on or dealt to American reproductive and public health. That is the high prevalence of trying-to-conceive problems (sub-fertility and infertility) and at the same time the very high rate of unintended pregnancies.

Lion_Hunt_Mosaic in Pella

Lion_Hunt_Mosaic in Pella

zb.jpg

zb.jpg

While many proponents of chemical contraception minimize or gloss over the side effects of contraceptive chemicals, it is known that “OCPs (oral contraceptive pills) have several known metabolic effects including increased production of clotting factors resulting in increased risk of venous thromboembolism, increased gallstone formation during the first year of use, and increased risk of liver adenomas (Speroff and DeCherney 1993)” – cited from Ther Clin Risk Manag. 2008 October; 4(5): 905–911 (paper from University of Vermont College of Medicine and Reproductive Endocrinology and Infertility, Women’s Health Care Services)

That said, studies mainly focus on side effects such as amenorrhea, the incidence of breakthrough bleeding and spotting, compliance, discontinuation rates or patient satisfaction, headaches, genital irritation, tiredness, bloating, and menstrual pain.

To cite from said medical publication “Evaluation of extended and continuous use oral contraceptives”, Ther Clin Risk Manag. 2008 October; 4(5): 905–911 QUOTE [emphasis mine]:

In a normally menstruating woman who is not taking contraceptive hormones, progesterone is only present in appreciable quantities during the luteal phase of the menstrual cycle [meaning: after ovulation], after the development of the endometrium. When combination OCPs are administered, the effect of the progestational agent takes precedence over the estrogen component in the reproductive tract, and the endometrium demonstrates this progestin effect (Moyer and Felix 1998). The result is a thin, decidualized (transformed) endometrium with atrophied glands that is not receptive to embryo implantation. Progestins also cause thick, impermeable cervical mucus, preventing sperm from reaching the uterine cavity, and also decrease tubal mobility, altering the movement of sperm and oocytes through the fallopian tube (Johnson et al 2007; Rossmanith et al 1997) END OF QUOTE.

This is consistent with the Erik Odeblad findings about the fine structure of the cervical tissues. http://humrep.oxfordjournals.org/cgi/content/full/18/9/1782

Edward_Burne-Jones_Maria_Zambaco_1870

Edward_Burne-Jones_Maria_Zambaco_1870

Further to the examples of studies about the mainly short-term effects of chemical contraception, here are examples of published findings about the harmful long-term effects of the sex steroid chemicals administered to healthy women. This is not a systematic review, merely a couple of examples.

BONE HEALTH:

The conclusion of “Effects of Depot Medroxyprogesterone Acetate and 20 μg Oral Contraceptives on Bone Mineral Density” [Obstet Gynecol. 2008 October; 112(4): 788–799]is as follows:

QUOTE Use of very low-dose OCP (Oral Contraceptive Pill) may result in a small amount of bone loss. DMPA (depot medroxyprogesterone acetate) use results in greater bone loss, but this is largely reversible at the spine. Use of very low-dose OCPs after DMPA discontinuation may slow bone recovery.

As a result, the Food and Drug Administration issued a warning in 2004 advising women to limit its use to ≤2 years.

Oral contraception (OC) containing only 20 μg ethinyl estradiol (EE) may also adversely affect bone health, especially if used during adolescence. END OF QUOTE [emphasis mine].

HEART HEALTH:

According to J Clin Endocrinol Metab. Author manuscript; available in PMC 2011 November 9 (Published in final edited form as: J Clin Endocrinol Metab. 2007 August; 92(8): 3089–3094), “whether OCP use in healthy young women is associated with increased CV (cardiovascular) risk is controversial. However, a recent meta-analysis of 14 studies showed that current use of low-dose OCPs increased the risk for myocardial infarction by 84% (37). More data are available regarding CV risk associated with estrogen/progestin use in older women… The Heart and Estrogen/Progestin Replacement Study showed an early increase in events and no benefit overall in women with known CV disease, and the Women’s Health Initiative (WHI) trial demonstrated an increase in CV events in healthy women (38, 39).” END QUOTE.

René Boyvin, The rape of Europa, c. 1545-55

René Boyvin, The rape of Europa, c. 1545-55

In Greek mythology Europa (Greek Ευρώπη Eurṓpē) was… seduced by the god Zeus in the form of a bull, who breathed from his mouth a saffron crocus[14] and carried her away to Crete on his back… and so see Wikipedia for the whole story. Oh, and should this not be clear, the metaphor here pertains to the man-made OCP [Oral Contraceptive Pill] accomplishment…

Max Beckmann, The rape of Europa (1933)

Max Beckmann, The rape of Europa (1933)

Returning to Odeblad’s results on the consequences of the Pill for the cervix uteri, that is on how contraceptive chemicals make it difficult to conceive later – and reiterating the take-home message put forward previously in “About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with”:

Natural aging of cervical S crypts (= cervical aging of a woman never pregnant and never on the Pill):

S crypts, which are needed for conception, are down to 20% at 40 years of age, at the natural aging rate -2% per year. Here you have the reason why a too mature age leads to sub-fertility and to infertility. My remark: The optimal age for motherhood has always been and always will be the early twenties of a woman’s life.

Atrophy acceleration effect of 10 years on the Pill:

S crypts are down to mere 10% at 40 years of age. Here is why it’s not nice to fool Mother Nature, why it’s not good to mess with her design. Fertility is drastically reduced. The Pill is an archetypal anthropogenic Endocrine-Active Compound [man-made EAC]. It was brought up previously in this blog how there are very many of these EACs, all insulting the female body and health; some – like chemical contraceptives – by design. Having invoked the design, I am reminded that the original designers of the Pill had no idea about contraception – they were pushing the frontiers of steroid chemistry… (not this particular application of one kind of steroids).

Atrophy slow-down or beneficial effect of pregnancies:

S crypts only down to 40% at 40 years of age. Here you see Mother Nature’s design in action. Pregnancy slows down the inherent rate of natural cervical aging (atrophy, deterioration). The effect of 4 pregnancies was measured in the Odeblad research. This is not to argue for 4 pregnancies per lifetime – it’s merely how the difference between with and without was made more “easily” measurable in the very difficult studies.

And again, the bottom line is this: “After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced. …S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced.” END QUOTE.

In case you’d like to view the Carlo Adelio Galimberti picture accompanying the concluding words, please re-visit the cited earlier post. The concluding words were and still would be: While the story of Laodamia and Protesilao is touching, I merely want to ask that girls, ladies and their physicians do not moon the messenger.

P. S.

Vaclav Havel would smile at the image of “mooning” Laodamia. I smile at the thought of his riding the children’s scooter (kolobezka) along Saint Peter’s heavenly corridors (looking for Olga? Since Pani Dagmar remained down there?). He reportedly did that scooter-running in the “labyrinthine” corridors of Prague Castle…

STOP PRESS

And now, 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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About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with

June 27, 2010

I have taken it upon myself to popularize Prof. Erik Odeblad’s classic findings about the biophysics of the tissues and secretions of cervix uteri, and how they translate into reproductive physiology and hence to reproductive medicine – at home and in the doctor’s office.

Emeritus Professsor Erik Odeblad

  Emeritus Professor Erik Odeblad    “The cervix is a precision organ as complex as the eye”

My ulterior motive is that I want to be understood when harking back to the British commercial’s exclamation that warned about too arrogant an attitude towards Mother Nature. Or, maybe I aim at the wisdom of the saying (“It’s not nice to fool Mother Nature!”) to be appreciated particularly within the given field of endeavor and/or endeavour – that is, reproductive management. Even if it were only in a segment of it.

In the Alphabet of bioZhena (which is no Alphabet of Ben Sira, though we model on it somewhat), https://biozhena.files.wordpress.com/2007/11/aaee-the-alphabet-of-biozhena.pdf , there is an entry about Atrophy and what it does to a woman as years go by, how “atrophy of mucosal surfaces takes place, accompanied by several problems.”

Jan Amos Komenský (Comenius) Says Farewell to...

Jan Amos Komenský (Comenius) Says Farewell to…

In this blog post I focus on aging – and thus atrophy – of the cervix, leaving aside the inevitable corresponding phenomena in other parts of the reproductive system.

The focus on the cervix is due to bioZhena’s focus on the cervix… which in our scheme of things is the supreme monitor of the complex reproductive goings on that Mother Nature designed in order to cope with all that complexity. After you’ve read the Alphabet article on atrophy, you might scroll down to the entry there about the cervix, which will take you also through cervical cancer and cervical mucus, besides a couple of other things cervical. That will or would be a nice preparation for, or introduction to, what follows.

Prof. Erik Odeblad's sketches from www.woombeuskadi.org...4_erik_odeblad(secrecion_cervix).pdf 13 February 2008

Two sketches by Emeritus Professor Erik Odeblad to illustrate his saying, “The cervix is a precision organ as complex as the eye”. Click (right-click) on the image to see the details. And read on about the details. The fine structure of the cervical canal wall, schematized on the right, is based on examination of mucus samples obtained with a suction syringe from the various parts of the cervical canal of human volunteers for physico-chemical examination.

When, at the inception of the project, we decided to focus on the given part of the anatomy, Erik Odeblad’s work logically and inevitably became a part of the background. He used the NMR (nuclear magnetic resonance) technique of physical chemistry to perform the complicated investigation of cervical mucus, and he produced the classical evidence for the difference between the “fertile” mucus macromolecules that allow the passage of the sperm, and the “infertile” cross-linked glycoprotein molecular network that does not. (To this day I remember his usage of “undulations”…)

In fact, this early information, which involved the thiol-disulfide (sulphydryl-disulphide) redox couples in the glycoprotein macromolecule, had much to do with our early hypothesis of the mechanism of our measurements. Never mind that his work was in the context of the subjective self-examination used in NFP, which did not work for the female member of the team! Had it worked for her, there would probably not be any Ovulona™ for monitoring folliculogenesis in vivo (FIV™ – which has utility well beyond fertility status determination)!

With atrophy being the general biological aspect of aging (and with the initially very large number of ova or eggs in the young female’s ovaries decreasing as she matures and ages), the cervix similarly “undergoes a natural process of development and aging. The surface area of the cervix that is given over to the mucus secreting glands [“crypts”] gradually diminishes with age.”

Odeblad defines three types of the (endo)cervical glands, which he (and others too e.g. Embryology.CH and Eurocytology.EU since at least the 1970s) calls the “crypts”:

  • S crypts produce S mucus, which forms string-like channels and provides transport (“swimming lanes”) for sperm cells. (“Produces a wet, lubricative sensation at the vulva.” That’s for the NFP sympto-thermal method use, the Billings method and/or the Creighton Model NaProEducation Technology method, the classical NFP or FAM – the latter, Fertility Awareness Method, publicized by Ms. Toni Weschler’s 2002 book Taking Charge of Your Fertility .)
  • L crypts produce L mucus, which eliminates low-quality sperm and provides a structure to support what he calls the S and the P mucus. P is a reference to the so-called Peak mucus of NFP or FAM.
  • G crypts produce G mucus, which is “an impenetrable gestagenic mucus formed in the lowest cervical crypts. Prevents sperm entry to the cervix and is part of the immune system which protects the woman’s reproductive system from infection.” A remark from dictionary.com: gestagen (jěs’tə-jən, -jěn’) n. A substance, such as a steroid hormone, that affects the uterus in a manner similar to progesterone. And a remark from a scientific commentator: This G mucus is characterized by the oxidized state of the mentioned redox couples, causing cross-linking in the glycoprotein mucin, which prevents microbes including sperm from entering. Visualize this as closed -S—S- gates (as opposed to the open gate form -SH   HS- of the “reduced” state of the redox couples; “reduced” meaning “electronated and hydrogenated”, the opposite of “oxidized”).
Mondrian_Evolution

Mondrian_Evolution

There are three fundamental principles at work.

1. Natural baseline aging, and this is fundamental – a more or less linear decrease in the number of all three kinds of these glands or crypts, at somewhat different rates: S the fastest, L somewhat slower, G slower still.

2. Slow-down of the aging atrophy by pregnancy.

3. Acceleration of the aging atrophy by the Pill [and/or by other endocrine-active compounds, EACs – this is a logical extrapolation, speculative, but must be assumed].

Now, then.

1. Natural baseline aging, fundamental – a more or less linear decrease in the number of all three kinds of these glands or crypts:

“The number of S crypts decreases from teen age. They are first replaced by L crypts starting at the base of the cervix. Later G crypts replace the L crypts.”

Thus, from Odeblad’s graph [rate reckoned from 15 yrs old to 40 yrs old]:

S crypt baseline decrease or diminution (or atrophy) rate:

50% / 25 years = 2% per year.

At 50 years old, S crypts are at some 10%.

Profile crypts baseline never pregnant never on the Pill

Profile of cervical crypts of a baseline woman – never pregnant & never on the Pill

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

for a woman who goes through life without pregnancy or use of the Pill.

This is a baseline profile.

Here is Erik Odeblad’s schematic of the crypts on the surface of the cervical canal:

Cervix of a 20 year old virgin

Carefully mapped lateral wall of the cervix of a 20 year old virgin           (reported by Emeritus Professor Erik Odeblad, Department of Medical Biophysics, University of Umeå, S-90187, Umeå, Sweden)

This is Professor Odeblad’s artist’s impression of cervical mucus secretions:

Mucus secretions

Schematics of cervical mucus secretions

Key to colors:

Blue         = S mucus

Yellow     = L mucus

Red          = G mucus

Green      = P mucus of which there are several sub-types

Pink         = Z granules

Professor Odeblad’s explanatory notes:

Z granules – the enzyme in the Z granules combines with the P mucus to create a liquefying effect.

P mucus – there are a number of sub-types of this mucus, the most relevant for fertility are P2 and P6. P2 could be present as early as the beginning of the fertile phase possibly having a role in liquefying the G mucus. P6 is mostly confined to the upper part of the cervix, occurring close to the Peak of fertility, and having a role in conveying sperm. It creates a very wet and lubricative sensation at the vulva.

F mucus – comes from the cells scattered throughout the length of the cervical canal and has no known special function.

For a recent evidence of four different morphological mucus types, namely L, S, P and G, see “Morphological characterization of different human cervical mucus types using light and scanning electron microscopy” by M. Menárguez, L.M. Pastor and E. Odeblad, Human Reproduction, Vol. 18, No. 9, 1782-1789, September 2003 –  http://humrep.oxfordjournals.org/cgi/content/full/18/9/1782

Citation: “The distribution of crypt zones in the cervix depends on age, number of pregnancies and use of contraception. In a non-pregnant woman, aged 25–30years and not having used contraception, the cervix averages 22 mm in length and 6 mm in diameter at ovulation. The crypt distribution starting from below and moving upwards is as follows: the G crypts dominate in the lowest 4–5 mm; then there is a zone of L crypts occupying the next 9–10 mm; this is followed by the S zone, for 5–6 mm; and the highest 3–4 mm contains the P crypts.”

When you read the paper, you detect that he has a very special knack for sampling the respective mucus types from the said crypts. Hat off! Work with human experimental subjects is no stroll in the park, to put this mildly.

2. Slow-down of atrophy aging by pregnancy:

Profile crypts 4x pregnant

Profile of cervical crypts of a 4x pregnant woman

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

for a woman who goes through life with four pregnancies and no use of the Pill.

Pregnancy – S crypt diminution rate from Odeblad’s graph

[4 pregnancies, no Pill, rate reckoned from 15 yrs old to 40 yrs old]:

30% / 25 years = 1.2% per year.

At 50 years old, S crypts are at some 20%.

3. Acceleration of atrophy aging by the Pill [and/or by other endocrine-active compounds, EACs – a logical extrapolation]

Profile of cervical crypts of a woman on the Pill

Representative profile of cervical crypts

(percentage of cervix occupied by active crypts)

for a woman who goes through life without pregnancy and uses the Pill for 10 years

Pill – S crypt diminution rate from Odeblad’s graph

[no pregnancy, Pill for 10 years (18 to 28 yrs old), rate reckoned from 15 yrs old to 40 yrs old]:

60% / 25 years = 2.4% per year.

At 50 years old, S crypts are at some 5%.

This includes the slow down of the diminution gradient during the last 12 years of no Pill.

Compare this with diminution/atrophy rate during the 10 years on the Pill:

65% – 25% = 40% / 10 years = 4% per year.

This is double the baseline rate of cervical atrophy.

It’s more than 3 times higher than the pregnancy-slowed atrophy rate.

Three concluding remarks by Prof. Odeblad:

“Regression when taking the Pill is different for estrogen-dependent crypts (L and S) and progesterone-dependent crypts (G) which may in part overdevelop.”

“The study of the effects of contraceptive pills on the cervix is a difficult task. A considerable amount of work is required for each patient and the time required spans many years, up to 10 years or more. Many women also want to change to other pills or to other methods of contraception, or perhaps now want to become pregnant. It also happens that some pills are withdrawn from the market. To these difficulties are added the normal age changes in the cervix and the dynamic processes which are of constant occurrence. After 3 and up to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced.” (“Some Notes on the Cervical Crypts”, Dr E. Odeblad, Bulletin of the Ovulation Method Research and Reference Centre of Australia, Vol 24 No 2 June 1997, p31)

Citations and graphics reproduced from http://www.billings-ovulation-method.org.au/act/cervix/ageing.shtml .

“Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural oestrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced. Treatment is difficult.” He also wrote: “After 3 to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced … A pregnancy rejuvenates the cervix by 2-3 years, but for each year the Pill is taken, the cervix ages by an extra year.” Web reference:  http://www.billings-ovulation-method.org.au/act/pill.html .

Comment on implications for treatments of certain symptoms

For example, the suggested method [Weschler, Toni (2002). Taking Charge of Your Fertility (Revised ed.). New York: HarperCollins. p. 52] of thinning cervical mucus to help achieve pregnancy by taking the OTC expectorant drug guaifenesin, which is thought to act by increasing the volume and reducing the viscosity of secretions.

The drug is also used to treat the symptoms of primary dysmenorrhea [severe uterine pain during menstruation ] where another treatment of choice is combined oral contraceptives [COCs]. Such treatments are administered to adolescents as well as to mature women because dysmenorrhea is a very common and serious problem (25% of women and up to 90% of adolescents ).

In both cases, the expectorant and the contraceptives are administered without knowledge of their mechanism of action in the given problem. Focus is on treating symptoms, not the underlying causes. The patient is the detector of any effect. How does the expectorant drug use correlate with the secretions of the different types of cervical mucus on the one hand, and with the folliculogenesis cyclic profile on the other? Is there any connection? If not, what does the drug do to the different crypts? And what the COCs do to them?

Is the expectorant so selective that it might do the right thing? Reduce type G? Enhance type S mucus? Does oxidation of the guaifenesin help reduce the cross-linked mucin type G in the cervical canal? As simple and pretty as that? (Even prettier if guaifenesin were not to be an EAC, an endocrine-active compound … which inactivity does not look likely – http://www.who.int/ipcs/publications/en/ch3.pdf .)

Would it not be nice to have a rationale for how the small guaifenesin molecule can have a good effect on both sub-fertility/infertility and dysmenorrhea?

Could it be that guaifenesin works bioelectrochemically in the same oxidation-reduction (redox) manner on the enzyme cyclooxygenase in the prostaglandin cascade, which is a cascade of redox reactions – producing an anti-inflammatory effect that translates as suppression of pain? (On a personal note, why not capitalize here at least conceptually on our ancient Wellcome Research Labs work, even before receiving – presumably – the first pension money from Glaxo Smith Kline?)

It’s easier to contemplate in general the effect of the contraceptive drug, which will presumably depend on the contents of the estrogenic and gestagenic components (modeling on Odeblad’s findings)…

Is there a connection between pain, cervix and ovaries, ovarian reserves? Maybe an abnormal depletion of, via ovarian cysts? Will the number of follicular waves and/or other features in the Ovulona cyclic profile – and correlated with ultrasound and MRI – show any such abnormality? Might the Ovulona be useful for diagnosis here, convenient, simple (inexpensive)? Wouldn’t that be nice?

Is cyclooxygenase inhibition detected by the cervix, does it show in the cyclic profile? Does said prostaglandin synthesis inhibition alter the number of follicular waves – while reducing the pain?

Answers to questions like these are needed. Keep in mind that ovulation is an inflammatory process, and since we detect it in the cyclic profile, it is reasonable to pose the above prostaglandin theory questions about the COX-2 (cyclooxygenase) inhibition.

Summarizing Odeblad’s results and the take-home message:

Baseline outcome of cervical S crypts aging: S crypts down to 20% at 40 years of age. Here you have the reason why mature age leads to sub-fertility and to infertility.

Atrophy slow-down effect of 4 pregnancies: S crypts down to 40% at 40 years of age. Here you see Mother Nature’s design in action. Pregnancy slows down the inherent rate of cervical aging (atrophy, deterioration). Naturally, this is not to argue for 4 pregnancies per lifetime – it’s merely how the effect was made measurable.

Atrophy acceleration effect of 10 years on the Pill: S crypts down to 10% at 40 years of age. Here is why it’s not nice to fool Mother Nature, why it’s not good to mess with her design. The Pill is an archetypal anthropogenic Endocrine-Active Compound [man-made EAC], and it was brought up in the previous post how there are very many of these EACs, all insulting the female body and health, some – like chemical contraceptives – by design.

While the story of Laodamia and Protesilao is touching, I merely want to ask that girls, ladies and their physicians do not moon the messenger.

Laodamia

STOP PRESS

And now, 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/

About Clomid, Serophene or, generically, clomiphene citrate. A critical look, part 1.

June 23, 2010

In relation to folliculogenesis, the mechanism of menstrual cycling, which we monitor in vivo – to get away from drugs as much as possible.

Last night I re-tweeted this:

RT @FertilAidAmy What is Clomid…? http://blog.fairhavenhealth.com/ = it’s NOT recommended to take it for >6 cycles, and it causes decreased fertile mucus

Then I found that there is no entry about Clomid in the Alphabet of bioZhena. Yet, Clomid is a very frequently administered medication for women with difficulty conceiving, “prescribed to women that are trying-to-conceive to induce ovulation. Clomid is often prescribed to women with irregular cycles that either experience irregular ovulation or don’t ovulate at all” (http://blog.fairhavenhealth.com/ ).

30% of women or couples cannot get pregnant

Clomid was also involved in a peculiar episode when a business-incubator director took me once to a local hospital’s young lady gynecologist thinking that, because she was written about in the local newspaper, she was just right for bioZhena Corporation’s quest for good people and/or “strategic allies”. Instead, the take of the young physician, who took several calls from upstairs during the “interview”, was something along the lines, “I don’t see what’s in it for me with your technology. When they [subfertility sufferers] come to us, we put them on Clomid, and that’s that…”.

dali - longlegs_large

Dali - Longlegs

Well, let’s look at what the “that’s that” is about. The referenced tweet mentioned, within the allowed 140 characters, two features. One, that Clomid should not be taken for more than 6 menstrual cycles. And two, that it is known to reduce the amount of the all-important fertile mucus, which is the cervical mucus form occurring only during the run up to ovulation. This essential temporary change is for the purpose of opening the cervical canal for the penetration of the sperm and, in fact, for what is called the capacitation of the sperm. At all times outside of the fertile window, the fertile mucus is replaced by the protective type of cervical mucus, which prevents the entry of microbes including sperm into the uterus and beyond.

For a concise overview of this essential mucus, read the article Cervical mucus (under C) in the Alphabet of bioZhena, at  https://biozhena.files.wordpress.com/2007/11/aaee-the-alphabet-of-biozhena.pdf . There we cite a noted expert on the subject, Dr. Erik Odeblad, and the gist of his message is: “Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural estrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced.”

You can imagine that this will have something to do with the reason why the woman becomes a patient and is now prescribed the fertility drug.

One other thing about the drug is the issue of the official “10-per-cent possibility that Clomid could produce twinning”, described by a physician’s blog post at KevinMD.com about “one of the largest malpractice awards in Canadian history. At issue is how the patient understood the discussion of the risks of Clomid”: http://to.ly/5cE7 .

Sublime moment by Salvador Dali, 1938

Sublime moment by Salvador Dali

Clomid is the brand name for the fertility drug clomiphene citrate. Clomiphene citrate may also be sold under the brand name Serophene or as the generic version called clomiphene citrate (http://to.ly/5cIc ).

Here is a bit more scientific take on how it works, cited from Wikipedia (http://en.wikipedia.org/wiki/Clomifene ):

Therapeutically, clomiphene is given at day 2 of menses [menstruation]. By that time, FSH level is rising steadily, causing development of a few follicles [in the ovary].

Let’s interject a clarification: This timing is called the recruitment stage of folliculogenesis, during which LH induces an “angiogenesis” factor from the theca cells, increasing the blood supply and estrogen synthesis by the recruited cohort of follicles.

The term “selection” indicates the reduction of the recruited group of follicles down to the species-characteristic ovulatory quota, which in women and related primates is one. Selection is the culmination of recruitment on day 6 ± 1. “Typically only one of the two ovaries sponsors recruitment and selection of the single dominant follicle, which is destined for ovulation.” We detect the selection stage as the first marker in our ovulographic™ (or folliculogenesis in vivo™) cyclic profile. Refer to the bioZhena tech pitch page http://to.ly/xE6 and/or to http://to.ly/MJU , http://to.ly/MWl .

Back to the language of the Wikipedia article: Follicles in turn produce the estrogen, which circulates in serum. Clomiphene acts by inhibiting the action of estrogen on the pituitary [gland, or hypophysis, in the brain]. [It] binds to estrogen receptors and stays bound for long periods of time.

This prevents normal receptor recycling and causes an effective reduction in hypothalamic estrogen receptor number. As a result, the body perceives a low level of estrogen… Since estrogen can no longer effectively exert negative feedback on the hypothalamus, GnRH secretion becomes more pulsatile, which results in increased pituitary gonadotropin (FSH, LH) release. Increased FSH level causes growth of more ovarian follicles, and subsequently rupture of follicles resulting in ovulation. END OF QUOTE.

Dali - Geopoliticus Child Watching the Birth of the New Man (1943)

Salvador Dali - Geopoliticus Child Watching the Birth of the New Man

From another Wikipedia article, about GnRH (http://en.wikipedia.org/wiki/GnRH ):

At the pituitary, GnRH [Gonadotropin Releasing Hormone (synthesized and released from neurons within the hypothalamus )] stimulates the synthesis and secretion of the gonadotropins, (that is) follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These processes are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and estrogens. Low-frequency GnRH pulses lead to FSH release, whereas high-frequency GnRH pulses stimulate LH release. …the frequency of the pulses varies during the menstrual cycle, and there is a large surge of GnRH just before ovulation.

To reiterate, Clomiphene acts by inhibiting the natural action of estrogen on the pituitary gland in the brain, interfering with – or, shall we say, altering, manipulating – the process of folliculogenesis. Women’s health revolves around folliculogenesis and its complex control mechanism by the brain and by the ovaries.

To give you a sense of said complexity of the biology we are working with when we monitor folliculogenesis in vivo, we cite the specialist, Dr. Ernst Knobil: “The mechanism is believed to involve the circhoral* clock of the hypothalamic GnRH pulse generator, on which the circamensual** ovarian clock is obligatorily dependent”. [*Occurring cyclically about once an hour, pulses from the brain; ** about once a month.] From Knobil’s memorial lecture The Wisdom of the Body Revisited, available online at http://physiologyonline.physiology.org/cgi/content/full/14/1/1 .

Sleep by Salvador Dali, 1937

During the reproductive years, pulse activity is critical for successful reproductive function as controlled by feedback loops. Cited in conclusion from the Wikipedia GnRH article referenced above. (The Wikipedia also has an article about the cervix and cervical mucus, at http://en.wikipedia.org/wiki/Cervical_mucus#Cervical_mucus .)

15- Word(le) greetings from bioZhena's follicular waves

15- Word(le) greetings from bioZhena's follicular waves

A wordle is a toy for generating “word clouds” from text.

In this case the entire bioZhena’s Weblog as it was in November 2009 — 15 most prevalent words.

It is advisable – and safer – to go about TTC, Trying To Conceive, without the use of chemicals, especially man-made chemicals, and note that herbal preparations are chemicals too. Monitoring (measuring) the effects of anything you ingest is basically a must, if you do not play “Russian roulette” with yourself, your offspring, your family.

The above wordle, the “greetings from bioZhena’s follicular waves”, is a reminder that, before resorting to the chemical route, the innocuous “right time” approach is indicated (because it does not go against – it goes with – the natural biology of the body).

Have you noticed that the powerful Clomid is an estrogen agonist/antagonist? (Acting like estrogen or against estrogen. Tricky, yes? You bet. Or play roulette…)


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