Posts Tagged ‘stress’

What is the mechanism of stress and how does it affect reproduction. An update. And: Be a young mother!

May 28, 2012

Ovulona™-related published scientific findings by others about disruption of fertility, about PCOS or Poly Cystic Ovarian Syndrome, how stress suppresses ovulation, about the hypothalamic amenorrhea of stress and postpartum blues/depression, about a CRH placental clock which determines the length of gestation and the timing of parturition and delivery, and the role of CRH in premature labor. How old age affects folliculogenesis as a stressor. Even how acute stress may induce ovulation in women.

This is an update in May 2012 on scientific literature reviewed in biozhena.wordpress.com/2007/12/27/   For an easier read (as opposed to the excerpts from scientific papers) you may want to go to Stress and Your Fertility at http://natural-fertility-info.com/stress-and-your-fertility.html but Hethir’s article does not refer to the Ovulona™. It simply tells you that stress has a negative effect on your chances of getting pregnant.

Unlike in the 2007 blog post, in the present update I share the complete abstracts of publications (way further down), pointing out in the abstracts certain details by bold font highlighting. On occasion I also point out in bold italics after the given abstract how the paper relates to the bioZhena project and the Ovulona™ personal monitor.

But first, I offer summary comments on the relationship of given papers to the bioZhena project, along with some details excerpted from the abstracts. Search result item numbers are indicated – so you can correlate my summary with the full abstracts and references shown below (after the Alfons Mucha picture).

In March 2018 I am adding here for reference the links to the page on the Ovulona (as updated in 2017)

https://biozhena.wordpress.com/2007/12/11/the-ovulona/

and to the Home Page of bioZhena’s Weblog

https://biozhena.wordpress.com/home-page-of-biozhenas-weblog/

Now to the review of literature:

Item 16:

This paper is suggestive of the prospective diagnostically beneficial use of the Ovulona™ in the management of PCOS [Poly Cystic Ovarian Syndrome], expected to be possible due to PCOS-caused alteration of the cyclic profile (detected via the exocervix, as the cervix monitors the integrated effects of all the hormones).

… effect is mediated by the hypothalamus, as evidenced by similar LH release in response to exogenous GnRH. This may represent the physiological condition that underlies ovarian follicular cysts.

Item 22.-related:

By emphasizing the critical timing of stress, this paper points by implication at the importance of routine Ovulona monitoring of Folliculogenesis In Vivo™, particularly  for assisting women who have difficulty to conceive but also for those practicing natural birth control. In either case, detecting any delay of ovulation is crucial.

The effects of stress on reproduction depend on the critical timing of stress, the genetic predisposition to stress, and the type of stress. The effect of stress on reproduction is also influenced by the duration of the responses induced by various stressors. Prolonged or chronic stress usually results in inhibition of reproduction, while the effects of transient or acute stress in certain cases is stimulatory…

Item 43:

This paper is related to our finding of delayed ovulation in some of the experimental subjects of two pilot studies of Ovulona™ prototypes – an important and unique feature of the Ovulona monitor, considering our way of life, full as it is of stress and not only stress of the psychological kind.

… findings support the hypothesis that stress-like increments in plasma cortisol [= increasing amounts of cortisol in blood] interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges.

Item 67:

Again, the listed paper is related to the PCOS problem, as is the next publication.

A follicle becomes cystic when it fails to ovulate and persists on the ovary. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant, which is attributed to insensitivity of the hypothalamus-pituitary to the positive feedback effect of oestrogens. Altered metabolite and hormone concentrations may influence follicle growth and cyst development.

You will see below, in the full abstracts of the papers, that the reported experiments could not be performed with human subjects, and the last two abstracts selected from the veterinary literature search state the following.

Item 101:

Imposition of an experimental stressor suppresses GnRH/LH pulse frequency and amplitude. It is not yet clear whether delays in the surge are caused by interruption of the oestradiol signal-reading phase, the signal transmission phase or GnRH surge release. [Note: oestradiol is British spelling of estradiol, the most predominant form of estrogen.]

Item 102:

Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. … Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility.

What follows now is an analogous summary of the subsequent search on human (as opposed to animal) female fertility and stress.

Reviewing the few full abstracts with references, below, is highly recommended.

Item 3:

… These effects are responsible for the “hypothalamic” amenorrhea of stress, which is observed in anxiety and depression, malnutrition, eating disorders and chronic excessive exercise, and the hypogonadism of the Cushing syndrome. … Reproductive corticotropin-releasing hormone is regulating [those] reproductive functions [that have] an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. … Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.

Item 3.-related:

Acute stress may induce ovulation in women. … acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. … Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

Item related to the above:

The stress system has suppressive effects on female and male reproductive function. Corticotrophin-releasing hormone (CRH), the principal regulator of stress, has been identified in the female and male reproductive system. … It has been suggested that there is a “CRH placental clock” which determines the length of gestation and the timing of parturition and delivery. … animal studies to elucidate the role of CRH in… premature labor.

Two literature search results – whereby I consider old age to be a stressor – are noted (with only certain excerpts from the abstracts) at the end of the post, consistent with the previously proposed motto: Be a young mother!

Hints for why – WHY TO BE A YOUNG MOTHER (besides coping more easily with other stressors) – cited from said two papers:

#1. Impaired folliculogenesis and ovulation in older reproductive-age women.

#2. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. END OF QUOTE.

Literature search was initially performed as Related Articles for http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Link&LinkName=pubmed_pubmed&from_uid=10844239  = What is stress, and how does it affect reproduction?

Dobson H, Smith RF. Anim Reprod Sci. 2000 Jul 2;60-61:743-52. Review.

PMID: 10844239 [PubMed – indexed for MEDLINE] Related citations

Selecting articles more recent than 2000 (search result numbers indicated). Most of these articles – in the initial search – are reports about animal models. (The reported work is obviously also for the benefit of agribusiness – for its reproduction-dependent profitability.)

16.

An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle.

PMID: 12021048 [PubMed – indexed for MEDLINE]

Free Article

Related citations

Biol Reprod. 2002 Jun;66(6):1689-95.

An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle.

Gümen A, Wiltbank MC.

Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Abstract

Many mammals, including cattle, can develop ovarian follicular cysts, but the physiological mechanisms leading to this condition remain undefined. We hypothesized that follicular cysts can develop because estradiol will induce a GnRH/LH surge on one occasion but progesterone exposure is required before another GnRH/LH surge can be induced by estradiol. In experiment 1, 14 cows were synchronized with an intravaginal progesterone insert (IPI) for 7 days, and prostaglandin F(2alpha) was given on the day of IPI removal. Estradiol benzoate (EB; 5 mg i.m.) was given 3 days before IPI removal to induce atresia of follicles. Cows were given a second EB treatment 1 day after IPI removal to induce a GnRH/LH surge in the absence of an ovulatory follicle. All cows had an LH surge following the second EB treatment, and 10 of 14 cows developed a large-follicle anovulatory condition (LFAC) that resembled follicular cysts. These LFAC cows were given a third EB treatment 15 days later, and none of the cows had an LH surge or ovulation. Cows were then either not treated (control, n = 5) or treated for 7 days with an IPI (n = 5) starting 7 days after the third EB injection. Cows were treated for a fourth time with 5 mg of EB 12 h after IPI removal. All IPI-treated, but no control, cows had an LH surge and ovulated in response to the estradiol challenge. In experiment 2, cows were induced to LFAC as in experiment 1 and were then randomly assigned to one of four treatments 1) IPI + EB, 2) IPI + GnRH (100 microg), 3) control + EB, and 4) control + GnRH. Control and IPI-treated cows had a similar LH surge and ovulation when treated with GnRH. In contrast, only IPI-treated cows had an LH surge following EB treatment. Thus, an initial GnRH/LH surge can be induced with high estradiol, but estradiol induction of a subsequent GnRH/LH surge requires exposure to progesterone. This effect is mediated by the hypothalamus, as evidenced by similar LH release in response to exogenous GnRH. This may represent the physiological condition that underlies ovarian follicular cysts.

This paper is suggestive of the prospective diagnostically beneficial use of the Ovulona™ in the management of PCOS [Poly Cystic Ovarian Syndrome] due to PCOS-caused distortion of the cyclic profile.

Sue Coe - Feed Lot, 1991, stone lithograph

Sue Coe – Feed Lot, 1991, stone lithograph
http://www.graphicwitness.org/coe/feedlot.jpg

22.-related (found as a related article of a related article)

Acta Vet Scand. 2008 Dec 10;50:48.

Stress and its influence on reproduction in pigs: a review.

Einarsson S, Brandt Y, Lundeheim N, Madej A.

PMID: 19077201 [PubMed – indexed for MEDLINE]

Free PMC Article

Division of Reproduction, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7054, SE-75007 Uppsala, Sweden. stig.einarsson@kv.slu.se

Abstract

The manifestations of stress, defined as a biological response to an event that the individual perceives as a threat to its homeostasis, are commonly linked to enhanced activity of the hypothalamo-pituitary-adrenal (HPA) axis and the activation of the sympathetic adreno-medullary (SA) system. Activation of the HPA system results in the secretion of peptides from the hypothalamus, principally corticotropin releasing hormone (CRH), which stimulates the release of adrenocorticotropic hormone (ACTH) and beta-endorphin. ACTH induces the secretion of corticosteroids from the adrenal cortex, which can be seen in pigs exposed to acute physical and/or psychological stressors. The present paper is a review of studies on the influence of stressors on reproduction in pigs. The effects of stress on reproduction depend on the critical timing of stress, the genetic predisposition to stress, and the type of stress. The effect of stress on reproduction is also influenced by the duration of the responses induced by various stressors. Prolonged or chronic stress usually results in inhibition of reproduction, while the effects of transient or acute stress in certain cases is stimulatory (e.g. anoestrus), but in most cases is of impairment for reproduction. Most sensitive of the reproductive process are ovulation, expression of sexual behaviour and implantation of the embryo, since they are directly controlled by the neuroendocrine system.

This paper suggests the importance of routine monitoring of Folliculogenesis In Vivo™ for assisting women who have difficulty to conceive.

43.

Endocrine basis for disruptive effects of cortisol on preovulatory events.

PMID: 15625239 [PubMed – indexed for MEDLINE]

Free Article

Related citations

Endocrinology. 2005 Apr;146(4):2107-15. Epub 2004 Dec 29.

Endocrine basis for disruptive effects of cortisol on preovulatory events.

Breen KM, Billings HJ, Wagenmaker ER, Wessinger EW, Karsch FJ.

Reproductive Sciences Program, University of Michigan, 300 North Ingalls Building, Room 1101 SW, Ann Arbor, Michigan 48109-0404, USA. breenk@umich.edu

Abstract

Stress activates the hypothalamo-pituitary-adrenal axis leading to enhanced glucocorticoid secretion and concurrently inhibits gonadotropin secretion and disrupts ovarian cyclicity. Here we tested the hypothesis that stress-like concentrations of cortisol interfere with follicular phase endocrine events of the ewe by suppressing pulsatile LH secretion, which is essential for subsequent steps in the preovulatory sequence. Cortisol was infused during the early to midfollicular phase, elevating plasma cortisol concentrations to one third, one half, or the maximal value induced by isolation, a commonly used model of psychosocial stress. All cortisol treatments compromised at least some aspect of reproductive hormone secretion in follicular phase ewes. First, cortisol significantly suppressed LH pulse frequency by as much as 35%, thus attenuating the high frequency LH pulses typical of the preovulatory period. Second, cortisol interfered with timely generation of the follicular phase estradiol rise, either preventing it or delaying the estradiol peak by as much as 20 h. Third, cortisol delayed or blocked the preovulatory LH and FSH surges. Collectively, our findings support the hypothesis that stress-like increments in plasma cortisol interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges. Moreover, the suppression of LH pulse frequency provides indirect evidence that cortisol acts centrally to suppress pulsatile GnRH secretion in follicular-phase ewes.

This paper is related to our finding of delayed ovulation in some of the experimental subjects of two pilot studies of Ovulona™ prototypes.

Steroids

67.

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review.

Vanholder T, Opsomer G, de Kruif A.

Reprod Nutr Dev. 2006 Mar-Apr;46(2):105-19. Epub 2006 Apr 6. Review.

PMID: 16597418 [PubMed – indexed for MEDLINE]

Free Article

Related citations

Reprod Nutr Dev. 2006 Mar-Apr;46(2):105-19. Epub 2006 Apr 6.

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review.

Vanholder T, Opsomer G, de Kruif A.

Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.

Abstract

Cystic ovarian follicles (COF) are an important ovarian dysfunction and a major cause of reproductive failure in dairy cattle. Due to the complexity of the disorder and the heterogeneity of the clinical signs, a clear definition is lacking. A follicle becomes cystic when it fails to ovulate and persists on the ovary. Despite an abundance of literature on the subject, the exact pathogenesis of COF is unclear. It is generally accepted that disruption of the hypothalamo-pituitary-gonadal axis, by endogenous and/or exogenous factors, causes cyst formation. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant, which is attributed to insensitivity of the hypothalamus-pituitary to the positive feedback effect of oestrogens. In addition, several factors can influence GnRH/LH release at the hypothalamo-pituitary level. At the ovarian level, cellular and molecular changes in the growing follicle may contribute to anovulation and cyst formation, but studying follicular changes prior to cyst formation remains extremely difficult. Differences in receptor expression between COF and dominant follicles may be an indication of the pathways involved in cyst formation. The genotypic and phenotypic link of COF with milk yield may be attributed to negative energy balance and the associated metabolic and hormonal adaptations. Altered metabolite and hormone concentrations may influence follicle growth and cyst development, both at the level of the hypothalamus-pituitary and the ovarian level.

Again, the paper is related to the PCOS problem, as is the next publication.

67.-related (found as a related article)

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release. [J Reprod Dev. 2006]

J Reprod Dev. 2006 Feb;52(1):1-11.

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release.

Todoroki J, Kaneko H.

Kimotsuki Livestock Hygiene Service Center, Kanoya, Kagoshima, Japan.

Abstract

Follicular cysts in cattle result from excessive growth of the dominant follicle without ovulation and still constitute a major reproductive disorder in this species. One key hormonal characteristic of cows with follicular cysts is the lack of an LH surge, although they have increased plasma estradiol concentrations. Another is a relatively high level of pulsatile secretion of LH that promotes continued growth of the dominant follicle. These LH characteristics seem to result from a functional abnormality in the feedback regulation of LH secretion by estradiol. Treatment with controlled internal drug release devices that increase circulating progesterone levels is effective in resolving follicular cystic conditions by 1) lowering pulsatile LH secretion and 2) restoring the ability of the hypothalamo-pituitary axis to generate an LH surge in response to an increase in circulating estradiol.

PMID: 16538030 [PubMed – indexed for MEDLINE]

Free full text

101.

Effects of stress on reproduction in ewes.

Dobson H, Fergani C, Routly JE, Smith RF.

Anim Reprod Sci. 2012 Feb;130(3-4):135-40. Epub 2012 Jan 26.

PMID: 22325927 [PubMed – in process]

Related citations

Anim Reprod Sci. 2012 Feb;130(3-4):135-40. Epub 2012 Jan 26.

Effects of stress on reproduction in ewes.

Dobson H, Fergani C, Routly JE, Smith RF.

School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Wirral, United Kingdom. hdobson@liv.ac.uk

Abstract

Stressors, such as poor body condition, adverse temperatures or even common management procedures (e.g., transport or shearing) suppress normal oestrus behaviour and reduce ewe fertility. All these events are co-ordinated by endocrine interactions, which are disrupted in stressful situations. This disruption is usually temporary in adult ewes, so that, when prevailing conditions improve, normal fertility would resume. Imposition of an experimental stressor (shearing, transport, isolation from other sheep, injection of endotoxin or insulin or cortisol infusion) suppresses GnRH/LH pulse frequency and amplitude. Part of the cause is at the pituitary, but effects on GnRH/LH pulse frequency and the GnRH/LH surge are mediated via the hypothalamus. It is not yet clear whether delays in the surge are caused by interruption of the oestradiol signal-reading phase, the signal transmission phase or GnRH surge release. Stressors also delay the onset of behaviour, sometimes distancing this from the onset of the pre-ovulatory LH surge. This could have deleterious consequences for fertility.

CAPT. AJIT VADAKAYIL's two images of stressed out women

CAPT. AJIT VADAKAYIL’s two images of stressed out women
Via Google search on “stressed woman in modern art painting”
These two images are from Ship Captain Ajit Vadakayil
http://ajitvadakayil.blogspot.com/2011/02/modern-abstract-art-and-picasso-capt.html
Original sources:
Weeping Woman by Pablo Picasso (1937)
http://www.inminds.com/weeping-woman-picasso-1937.html
and
untitled file saved as AASHIK+1+001.jpg
http://4.bp.blogspot.com/-NijqSqXo2Tw/TVkVQkpCmII/AAAAAAAADcU/rzleByUNJfg/s1600/AASHIK+1+001.jpg

102.

Glucocorticoids, stress, and fertility.

Whirledge S, Cidlowski JA.

Minerva Endocrinol. 2010 Jun;35(2):109-25. Review.

PMID: 20595939 [PubMed – indexed for MEDLINE]

Related citations

Minerva Endocrinol. 2010 Jun;35(2):109-25.

Glucocorticoids, stress, and fertility.

Whirledge S, Cidlowski JA.

Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, Durham, NC 27709, USA.

Abstract

Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]); 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.

At this point, let’s change the search tactics, by looking at Related Citations for this last one, which is clearly about human (as opposed to animal) female fertility and stress: http://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed&IdsFromResult=20595939

3.

Stress and the female reproductive system.

Kalantaridou SN, Makrigiannakis A, Zoumakis E, Chrousos GP.

J Reprod Immunol. 2004 Jun;62(1-2):61-8. Review.

PMID: 15288182 [PubMed – indexed for MEDLINE]

Related citations

J Reprod Immunol. 2004 Jun;62(1-2):61-8.

Stress and the female reproductive system.

Kalantaridou SN, Makrigiannakis A, Zoumakis E, Chrousos GP.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Ioannina, School of Medicine, Panepistimiou Avenue, 45500 Ioannina, Greece.

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis, when activated by stress, exerts an inhibitory effect on the female reproductive system. Corticotropin-releasing hormone (CRH) inhibits hypothalamic gonadotropin-releasing hormone (GnRH) secretion, and glucocorticoids inhibit pituitary luteinizing hormone and ovarian estrogen and progesterone secretion. These effects are responsible for the “hypothalamic” amenorrhea of stress, which is observed in anxiety and depression, malnutrition, eating disorders and chronic excessive exercise, and the hypogonadism of the Cushing syndrome. In addition, corticotropin-releasing hormone and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, corticotropin-releasing hormone is secreted in peripheral inflammatory sites where it exerts inflammatory actions. Reproductive corticotropin-releasing hormone is regulating [those] reproductive functions [that have] an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of labor. Circulating placental CRH is responsible for the physiologic hypercortisolism of the latter half of pregnancy. Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.

3.-related (found as Cited by 7 PubMed Central articles)

Reprod Biol Endocrinol. 2010 May 26;8:53.

Acute stress may induce ovulation in women.

Tarín JJ, Hamatani T, Cano A.

Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences, University of Valencia, Burjassot, Valencia 46100, Spain. tarinjj@uv.es

Abstract

BACKGROUND:

This study aims to gather information either supporting or rejecting the hypothesis that acute stress may induce ovulation in women. The formulation of this hypothesis is based on 2 facts: 1) estrogen-primed postmenopausal or ovariectomized women display an adrenal-progesterone-induced ovulatory-like luteinizing hormone (LH) surge in response to exogenous adrenocorticotropic hormone (ACTH) administration; and 2) women display multiple follicular waves during an interovulatory interval, and likely during pregnancy and lactation. Thus, acute stress may induce ovulation in women displaying appropriate serum levels of estradiol and one or more follicles large enough to respond to a non-midcycle LH surge.

METHODS:

A literature search using the PubMed database was performed to identify articles up to January 2010 focusing mainly on women as well as on rats and rhesus monkeys as animal models of interaction between the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes.

RESULTS:

Whereas the HPA axis exhibits positive responses in practically all phases of the ovarian cycle, acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. However, there are studies suggesting that several types of acute stress may exert different effects on pituitary LH release and the steroid environment may modulate in a different way (inhibiting or stimulating) the pattern of response of the HPG axis elicited by acute stressors.

CONCLUSION:

Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

PMID: 20504303 [PubMed – indexed for MEDLINE]

PMCID: PMC2890612

Free PMC Article

The above-related (found via their Ann N Y Acad Sci. 2006 Dec;1092:310-8 abstract titled “Reproductive” corticotropin-releasing hormone).

J Reprod Immunol. 2010 May;85(1):33-9.

Corticotropin-releasing hormone, stress and human reproduction: an update.

Kalantaridou SN, Zoumakis E, Makrigiannakis A, Lavasidis LG, Vrekoussis T, Chrousos GP.

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina Medical School, Ioannina, Greece. Sophia_Kalantaridou@hotmail.com

Abstract

The stress system has suppressive effects on female and male reproductive function. Corticotrophin-releasing hormone (CRH), the principal regulator of stress, has been identified in the female and male reproductive system. Reproductive CRH participates in various reproductive functions that have an inflammatory component, where it serves as an autocrine and paracrine modulator. These include ovarian and endometrial CRH, which may participate in the regulation of steroidogenesis and the inflammatory processes of the ovary (ovulation and luteolysis) and the endometrium (decidualization and blastocyst implantation) and placental CRH, which is secreted mostly during the latter half of pregnancy and is responsible for the onset of labor. It has been suggested that there is a “CRH placental clock” which determines the length of gestation and the timing of parturition and delivery. The potential use of CRH-antagonists is presently under intense investigation. CRH-R1 antagonists have been used in animal studies to elucidate the role of CRH in blastocyst implantation and invasion, early fetal immunotolerance and premature labor. The present review article focuses on the potential roles of CRH on the physiology and pathophysiology of reproduction and highlights its participation in crucial steps of pregnancy, such as implantation, fetal immune tolerance, parturition and fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis.

Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

PMID: 20412987 [PubMed – indexed for MEDLINE]

NOTA BENE or NOTE WELL: Chancy search result #1 (in our book, old age is a stressor):

J Clin Endocrinol Metab. 2003 Nov;88(11):5502-9.

Impaired folliculogenesis and ovulation in older reproductive aged women.

Santoro N et al.

… to test the hypothesis that older reproductive age [ORA >or= 45 yr old] women ovulate at a smaller follicle diameter and are more likely to produce multiple follicles during their menstrual cycle compared with mid-reproductive age [MRA 22-34 yr old] women. … ORA women were twice as likely to have multiple follicles as younger women. … grossly abnormal hormonal patterns were observed in some of the ORA women’s cycles. Other cycles demonstrated a failure of folliculogenesis. ORA women ovulated at a smaller mean follicle diameter … than younger women.

NOTA BENE or NOTE WELL: Chancy search result #2 (old age being a stressor):

J Obstet Gynaecol Can. 2011 Nov;33(11):1165-75.

Advanced reproductive age and fertility.

Reproductive Endocrinology and Infertility Committee; Family Physicians Advisory Committee; Maternal-Fetal Medicine Committee; Executive and Council of the Society of Obstetricians, Liu K, Case A.

Recommendations (excerpted from Abstract):

1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s.

2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive.

5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age.

6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman’s own eggs.

7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established.

8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40.

9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small.

Durer's Wife Agnes by Albrecht Durer, about 1494

Durer’s Wife Agnes by Albrecht Durer, about 1494
http://www.albrecht-durer.org/Durer%27s-Wife-Agnes.html

Although this literature search update is not necessarily complete, the blog post has grown long enough, so we better stop here. Enough food for thought for now… Don’t let all this stress you out! Just keep in mind: Be a young mother!

Oh, and do tell Uncle Rockefeller that Auntie Katharine (McCormick) made a little Big Mistake when she put her bets on chemistry and Cousin Margaret’s “magic pill”. Or is it the other Uncle that you are barbecuing with in Omaha, this Memorial Day?

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Stress and fertility: How stress affects the inherently narrow fertile window

February 2, 2012

This blog post appears as the third result in Google search on “bioZhena” (without the quote marks). The complete title is:

Stress and fertility

How stress affects the inherently narrow fertile window

To read the whole post, click on either of the antique-book images or on Reblogged from bioZhena’s Weblog:

Before you go there, here is a little update. New research into stress and fertility was published since I wrote the blog post in December 2007, and here is a summary of an article titled “Stress puts double whammy on reproductive system, fertility” (see http://esciencenews.com/articles/2009/06/15/stress.puts.double.whammy.reproductive.system.fertility ).

 

QUOTE: The new research shows that stress also increases brain levels of a reproductive hormone named gonadotropin-inhibitory hormone, or GnIH, discovered nine years ago in birds and known to be present in humans and other mammals. This small protein hormone, a so-called RFamide-related peptide (RFRP), puts the brakes on reproduction by directly inhibiting GnRH.

The common thread appears to be the glucocorticoid stress hormones, which not only suppress GnRH but boost the suppressor GnIH – a double whammy for the reproductive system. END QUOTE

 

Unlike any other fertility monitoring technology, bioZhena’s Ovulona™ is a Smart Sensor™ in vivo monitor of folliculogenesis. Unlike any other fertility monitor, the Ovulona is basically involved with the always-present stress responses – through monitoring certain end-organ effects on folliculogenesis. The other techniques monitor only this or that circulating hormone – not good enough. The end-organ effect(s) is what counts.

 

Again, to read the whole post, click on either of the antique-book images or on Reblogged from bioZhena’s Weblog

 

For a 2012 update go to What is the mechanism of stress and how does it affect reproduction. An update. And: Be a young mother! (Ovulona™-related published scientific findings by others about disruption of fertility, about PCOS or Poly Cystic Ovarian Syndrome, how stress suppresses ovulation, about the hypothalamic amenorrhea of stress and postpartum blues/depression, about a CRH placental clock which determines the length of gestation and the timing of parturition and delivery, and the role of CRH in premature labor. How old age affects folliculogenesis as a stressor. Even how acute stress may induce ovulation in women.)

bioZhena's Weblog

How stress affects the inherently narrow fertile window

Stress can do unwanted things to a woman and her menstrual cycle. In a nutshell, stress can make a woman completely infertile in this menstrual cycle (e.g., LPD, see below), or it can change the position of her fertile window (the time of ovulation included) within the menstrual cycle. Any of this can cause problems and lead to more stress…

The medical term is stress response, and it refers to the overall reaction of the organism to any adverse stimulus, whether it be of physical, mental or emotional kind, internal or external. The purpose is to adapt to challenge, and this goes on all the time. (C’est la vie! Real life is a never-ending series of stress responses.) Should the compensating reaction of the organism be inadequate or inappropriate, a pathological disorder may result.

The HPA axis, the immune system and the…

View original post 1,035 more words

Comment on Female sexual dysfunction treatment options

June 20, 2010

An excellent overview post appeared on the KevinMD.com blog, titled Female sexual dysfunction treatment options, written by Jill of All Trades, MD: http://www.kevinmd.com/blog/2010/05/female-sexual-dysfunction-treatment-options.html .

It is worthwhile to capture the introductory paragraphs of Jill’s post here:

Female sexual dysfunction has been reported in up to 40% of women, and described as causing actual distress in approximately 12% of women.

Michelangelo The Last Judgment, 2 cropped

Michelangelo, The Last Judgment, 2 cropped

Therefore, it is an important topic to familiarize with and screen for as a primary care physician, as many patients may not report these symptoms unless they are elicited during the history taking process of the patient encounter. Female sexual dysfunction is often multifactorial and complex; it is affected by such factors as depression and anxiety disorders, life stressors, interpersonal conflict between the couple, medication side effects, age, religious concerns, personal health, privacy issues, personal body image, substance and alcohol abuse, and hormonal influences.

In order to understand the necessary treatment options, it is important to understand the normal female sexual cycle. There are four phases:

1. Libido: the desire for sexual intimacy, through images or thoughts.

2. Arousal: the increase in heart rate, blood pressure, and respiratory rate, along with increased genital blood flow.

3. Orgasm: the peak of sexual pleasure, with rhythmic contractions of the pelvic muscles.

4. Resolution: the return to baseline with pelvic muscle relaxation.

Michelangelo The Last Judgment

Michelangelo The Last Judgment

The author then very nicely and concisely reviews the treatment options.

I posted the following comment, which at this writing was “awaiting moderation”. –

Thank you for an excellent overview.

I envisage that our Ovulona™ personal vaginal monitor (https://biozhena.wordpress.com/2007/12/11/the-ovulona™ ) will do two useful things for peri-menopausal women and their physicians (https://biozhena.wordpress.com/2008/10/06/ovulona-is-not-another-ovulation-kit ):

#1. Detect effect of any treatment on vaginal tissues and thus allow for personalization of therapy, titration of medications); and

#2. Allow vaginal delivery of therapeutic compounds.

The Ovulona should become a friendly companion tool for all women, to be routinely used from adolescence to peri-menopause (not only for reproductive management, its primary – or certainly initial – purpose).

Ref.: https://biozhena.wordpress.com/2007/12/18/menopause-hrt-and-biozhena/

Regards,

@bioZhena

Michelangelo, The Last Judgment, 2

Michelangelo, The Last Judgment, 2

To this, for the purpose of bioZhena’s Weblog, I would add a reminder about the significance of the problem of (tissue) atrophy, which the reader will find in The Alphabet of bioZhena (under A in the article titled Atrophy) at https://biozhena.files.wordpress.com/2007/11/aaee-the-alphabet-of-biozhena.pdf .

Atrophy means a wasting away, deterioration, or diminution, any weakening or degeneration (especially through lack of use). Read the article, you’ll see about genitourinary atrophy that leads to a variety of symptoms (in both sexes), affecting the quality of life.

And more, including about “estrogen therapy, which is invariably successful in reversing the atrophic problems. Relief from these problems often results in significant improvements in general well-being.”

In my comment above, #1 (detect the effect of treatment on vaginal tissues), the need for personalization of estrogen therapy is reflected, which requires the end-organ effect measuring tool that we provide. See also under E for End-organ effect in the Alphabet of bioZhena at https://biozhena.files.wordpress.com/2007/11/aaee-the-alphabet-of-biozhena.pdf .

Parturition means birthing (birth) and dystocia a difficult one

January 9, 2008

And what is a parturition alarm?

For these and other entries, see the Alphabet of bioZhena at

https://biozhena.wordpress.com/2007/11/28/the-alphabet-of-biozhena/

Parturition alarm:

This is a concept that has to do with the need to know when labor or delivery is beginning, because the birthing female may be in need of help.

At the time of writing the first Alphabet draft more than five years ago, an Internet search produced only one such technology, a pressure-sensing girth, suitable for the horse breeder only, because it utilizes the fact that the horse mare lies on her side only in the process of parturition. To illustrate, we borrow a nice picture from a more recent publication found in today’s search on parturition alarm, which search still shows a preponderance of equine innovations:

Equine birth alarm

In the originally noted publication, reference was made to some other method that would detect the emergence of the amniotic sac or of the foal from the vulva (vaginal orifice) but that was not a satisfactory solution. In the horse-breeding arena, about 5-6% of births require help. Various approaches to the birth alarm solution have been attempted.

These days, there are quite a few patents etc. found in the parturition alarm search. And even 5 years ago, a patent from New Mexico University should have been found because their intra-vaginal parturition alarm patent (basically for cows) was published in 1987.

In human obstetrics, where most births take place in hospitals, determining the right time of confinement would be very beneficial. bioZhena (and/or its sister company, bioPecus) will investigate our vaginal sensor technology – suitably modified – with a view to developing a parturition alarm applicable to any mammal.

Also relevant in this context is the implication of the Ovulona making available the menstrual cycle (folliculogenesis) data over many months or cycles before conception. This will enable a more accurate anticipation of the EDD, Expected Date of Delivery. You will understand this better below, under Parturition. I highly recommend that you check out Figuring Your Due Date, too – from the Midwife Archives.

Let us put it this way: Since this is the bioZhena blog (and not bioPecus, for veterinary tools), the EDD issue must be addressed first, before any parturition alarm developments. Because we are primarily concerned with the Rerum Naturare Feminina.

And it would still be of great interest to hear from an expert Latinist about the correct way of saying this in plural, the Natural Thing of Women, the Women’s Natural Thing…

This being a reference to /2007/12/16/cervix-uteri-and-seven-or-eight-related-things/ .

Parturition:

The process of giving birth; childbirth. [From Late Latin parturitio, from Latin parturitus, past participle of parturire, to be in labor.]

Parturition is illustrated at http://www.mhhe.com/biosci/esp/2001_saladin/folder_structure/re/m2/s5/ .

The illustration’s legend indicates that physicians usually calculate the gestation period (length of the pregnancy) as 280 days: 40 weeks or 10 lunar months from the last menstrual period (LMP) to the date of confinement, which is the estimated date of delivery of the infant [EDD].

Indubitably, due dates are a little-understood concept:

“Truth is, even if you know the exact date when you ovulated, you still can only estimate the baby’s unique gestational cycle to about plus or minus two weeks” [ http://www.gentlebirth.org/archives/dueDates.html ]. Why should that be? Because of the variability of your menstrual cycle lengths? (They vary even if you do not think so).

Statistically, the gestation time for human babies has a mean of 278 days and a standard deviation of 12 days, an uncomfortably large spread. The old Naegele Rule of a 40-week pregnancy was invented by a Bible-inspired botanist Harmanni Boerhaave in 1744 and later promoted by Franz Naegele in 1812. It is still believed to work fairly well as a rule of thumb for many pregnancies. However, the rule of thumb also suggests: “If your menstrual cycles are about 28 days, quite regular, and this is not your first child, your physician’s dating is probably fine. If your cycles are longer or irregular, or if this is your first child, the due date your physician has given you may be off, setting you up for all kinds of problems” (induction, interventions, C-section among them).

This is where the bioZhena technology can be expected to provide help, making it possible to reckon the EDD with recorded menstrual cycle (folliculogenesis history) data rather than merely with the LMP + 280 days. This, once properly researched, may be expected to have a significant impact on obstetric management. — Any comments?

It is ironic that, in this age of technological medicine, American women worry about their birthing process not being allowed to take its own natural course on account of an ancient method of predicting the EDD.

Ironically, the 40 week dogma – which is the gestational counterpart of the unacceptable calendar method of birth control (the so-called “Vatican roulette”) – does not reconcile the 295+ days of the 10 lunar months; and yet, at the same time, the U.S. has an unusually high perinatal death rate, resulting from high statistics of too early (preterm) labor. Quid agitur? See also under Gestation.

Dystocia or birthing difficulty:

Dystocia is difficult delivery, difficult parturition. From Latin dys-, bad, from Greek dus-, ill, hard + Greek tokos, delivery. Calf losses at birth result in a major reduction in the net calf crop. Data show that 60% of these losses are due to dystocia (defined as delayed and difficult birth) and at least 50% of these calf deaths could be prevented by timely obstetrical assistance. The USDA web site http://larrl.ars.usda.gov/physiology_history.htm is apparently no longer there but when it was it indicated that an electronic calving monitor was being developed to determine maternal and fetal stress during calving. These studies are important since they are leading the way for developing methods to reduce the $800 million calf and cow loss that occurs each year at calving in the USA’s beef herds.

In analogy with the superiority of in vivo monitoring of folliculogenesis versus tracking behavioral estrus (heat), in vivo monitoring of the progress towards parturition must be a priori a more promising approach.

The telemetric version of the BioMeter – the animal version of the Ovulona technology – will hopefully provide a tool for these efforts. Once tested on animals, human use will be a logical extension of the endeavor. (Or endeavour, should it take place in Europe! Smiley…)

Comment about the EDD and/or EDC issue, and request for input:

Again, EDD stands for Estimated Day of Delivery, while EDC stands for Estimated Day of Confinement.

Per Encyclopedia of Childhood and Adolescence, article Gestation Period and Gestational Age [ http://findarticles.com/p/articles/mi_g2602/is_0002/ai_2602000272 ], ” a gestation period of thirty-eight weeks (266 days) is calculated for women who are pregnant by a procedure such as in vitro fertilization or artificial insemination that allows them to know their exact date of conception.”

The Ovulona device from bioZhena will provide to the woman user a very simple means to record the day of any intercourse. In every cycle, whether pregnancy is planned or not. This must become a part of the routine. The information will be electronically recorded along with the daily or almost-daily measurement data inherent in the use of the Ovulona. With that menstrual cycling history data, this intercourse-timing information will be available for optional use by the woman’s physician(s).

Therefore, the routine use of the Ovulona will provide for an equivalent of the above-referenced 38-week (266 days) calculation available to the women receiving IVF or artificial insemination.

This alone should be an improvement on the current way of EDD/EDC assessment.

In addition, an investigation should be undertaken into the question of whether any inference can be drawn from the woman’s menstrual cycle history prior to the conceptive intercourse. Any comments on this would be welcome, even about anecdotal or subjective or tentative observations that may be available already. However non-scientific, however tentative, however uncertain an individual answer or input from you may be…

E.g., do women with more or less regular cycles tend to exhibit a regular gestation period, and vice versa?

And, certainly, what evidence is available in medical literature (or maybe in unpublished records?) about the outcomes of the IVF and/or artificial insemination pregnancies, i.e., about their documented gestation periods? Does the 38 weeks projection work? Always? If not always, can anything be correlated with any deviation?

Do women with distinctly irregular menstrual cycles tend to have non-regular gestation periods?

The complicating effect of first versus subsequent pregnancy has already been noted, of course…

Conceivably, there is no such preliminary info available, and we shall have to try and gather even these preliminary data in a systematic manner, but – no question asked, nothing learned… Public or private input would be appreciated.

Birthday, and how it relates to the bioZhena enterprise – eukairosic™ diagnostic tools

December 28, 2007

Today is a major anniversary related to the bioZhena enterprise. Namely, a round-number (and not small) birthday of the offspring whose begetting had much, if not everything, to do with the inception of the project.

The biologically educated member of the would-be parental team insisted that medical help would have to be the very last resort, as she did not wish to be poked in and subjected to the various medical procedures available in the country of the proud Albion (that, alas, no longer ruled the waves!), where this awakening was going on. The image of what she resented getting into is telling, and it’s not even the whole story.

Woman in stirups sketch

Awakening on the part of said couple, who till then took steps to minimize or theoretically avoid getting in the family way, owing to circumstances. As in too many instances the world over, the “awakening” was left until somewhat too late. I do not wish to talk about age specifics, but you probably know that particularly female fertility (more accurately put, fecundity or fecundability) decreases starting around or even before the Christ’s age, and so – in retrospect – it was no great surprise to find that achieving pregnancy was not as simple as expected. At the time, actually, this was a great surprise…

At the time, yours truly was not an expert in the field that deals with certain practicalities of the most important aspect of life, by which many of us mean procreation, reproduction, and its management. I am referring to some insight into the practicalities on the female side of things procreative, which insight was not there at the time – but the better half knew the basic fundamental that I now delight in referencing as eukairosic.

In a nutshell, the word refers to the right time, opportune time – exactly what we are about the strategic or “right time; the opportune point of time at which something should be done.” A window of opportunity is kairos time.

For more about this, the Wikipedia article can be recommended, at http://en.wikipedia.org/wiki/Kairos . Let’s cite: Kairos (καιρός) is an ancient Greek word meaning the “right or opportune moment,” or “God’s time” [sic; thus said – but this should say “gods’ time”]. The ancient Greeks had many gods, and two words for time, chronos and kairos. While the former refers to chronological or sequential time, the latter signifies “a time in between”, a moment of undetermined period of time in which “something” special happens. What the special something is depends on who is using the word. END QUOTE.

If you visit that article, you will probably understand why I would like to look at the possibility of adopting as our company logo QUOTE a monochrome fresco by Mantegna at Palazzo Ducale in Mantua (about 1510 C.E.) that shows a female Kairos (most probably Occasio)… UNQUOTE.

You will also appreciate that, since we are not theologians, and because “eu-“ is the Greek prefix meaning well or good or true or easy, my choice of the adjective that we want to trademark as descriptive of bioZhena’s wares is eukairosic™.

And so here, for the sake of accurate definition, is one other item from The Alphabet of bioZhena – /2007/11/28/the-alphabet-of-biozhena/

Fecundability and fecundity:

Fecundability is the probability of achieving pregnancy within one menstrual cycle – about 20% or maybe 25% in normal couples [sic; the probability depends on many factors, including age – vide infra, or see below].

Fecundity is the ability to achieve a live birth.

Fecundability is strongly influenced by the age of the partners, and it is maximal at about age 24. There is a slight decline at ages 24 – 30, and a rapid decline after age 30.

The words are derived from Latin fecundus, fecund, from the root of fetus, via Old French fecond. Fecund means fruitful in children, or prolific.

As for the eukairosic diagnostic tools, their utility goes beyond reproductive management. Due to folliculogenesis (menstrual cycling), even things such as administration of medications or certain diagnostic examinations must be performed at the right time within the menstrual cycle…

Scire quod sciendum

fecundoscitus!!! 🙂

Thus spoke the exegete and father of Barnaby and Petrushka, Vaclav Kirsner © 2007

 ‘To know what is to be known’.

What is the mechanism of stress, and how does it affect reproduction?

December 27, 2007
“When pushed too far, subfertility occurs”
Here is an ad hoc selection of a few abstracts from my files on psychoneuroimmunoendocrinology papers addressing ovulation, reproduction (folliculogenesis).

Abstracts of ad hoc selected papers about stress in reproductive physiology:

What is the mechanism of stress, and how does it affect reproduction?

The first few are representative of animal work, and then several abstracts represent the literature on stress in the human female. In between, let’s display our cyclic profile data on a non-baseline menstrual cycle with delayed ovulation. This record illustrates how our OvulonaTM device can detect the effect of stress on the course of the menstrual cycle. Non-baseline refers to any real-life female with all the stressors of our daily life, no baseline simplifications of conditions such as we need to try and approach what we would call ideality (at least in physical science we would…).

Should these abstracts turn out to be too stressful, then you may perhaps enjoy better another selection I just came across, Introduction to psychoneuroendocrinology volume: is there a neurobiology of love? http://cogweb.ucla.edu/Abstracts/NeuroLove_98.html

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Highlights:

possible pathway in the regulation of ovulation – stria terminalis to the amygdaloid complex in the monkey (Macaca fascicularis) – J Physiol. 1977

Characteristics of a ventral tract from the bed nucleus of the stria terminalis (BST) to the amygdaloid complex

from BST to the amygdala, and, since the neurones of BST contain estradiol, … this tract may be involved in the regulation of ovulation.

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New data on serotoninergic mechanisms in ovulation in the cyclic female rat – C R Seances Soc Biol Fil. 1979

These results provide support to the specificity of action of serotonin in the control of ovulation in the cyclic rat. They also suggest an interaction of serotonin and oestrogens in this control.

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the hypothalamo-pituitary-gonadal axis in the female rhesus monkey. – Ann N Y Acad Sci. 1993
inhibit the GnRH pulse generator

acute decrease in LH and FSH secretion.

This decrease in gonadotropin release may explain the deleterious effects of stress on the menstrual cycle. However, an acute decrease in gonadotropins following activation of the adrenal axis is not observed in the presence of estradiol.

Thus, during the menstrual cycle, a relative protection against the deleterious effects of acute stress may exist. How potent this protective mechanism is against repetitive stress is not known.

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What is stress, and how does it affect reproduction? – Anim Reprod Sci. 2000

stressors such as milk fever or lameness increase the calving to conception interval by 13-14 days, and an extra 0.5 inseminations are required per conception.

a variety of endocrine regulatory points exist whereby stress limits the efficiency of reproduction

stressors interfere with precise timings of reproductive hormone release within the follicular phase

opioids mediate these effects

there is a level of interference by stressors at the ovary

Reproduction is such an important physiological system that animals have to ensure that they can respond to their surroundings; thus, it is advantageous to have several protein mechanisms, i.e. at higher brain, hypothalamus, pituitary and target gland levels.

However, when pushed too far, subfertility occurs.

Non-baseline cycle with delayed ovulation

…stressors interfere with precise timings…

And the stressors may even cause the Ms. to forget her daily measurement, in spite of which the pattern is discernible and interpretable in terms of “go/no go” or “safe/unsafe” as some may put it; we just say FERTILE or NOT and leave it to the user to decide… And yes, the indication of the fertile day number will also be provided.

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The role of stress in female reproduction: animal and human considerations – Int J Fertil. 1990

Tonic, pulsatile gonadotropin secretion is inhibited by stress and by administered morphine, but morphine does not block the estrogen-induced preovulatory surge in primates.

Accordingly, impaired follicular development appears to be the most common cause of reproductive dysfunction attributable to stress in the human female

must take into consideration the many differences between the hormonal responses to stress in the human and laboratory animals.

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Development of the hypothalamic-pituitary-ovarian axis – Ann N Y Acad Sci. 1997

Onset of puberty is associated with a greater increase in LH pulse amplitude than frequency

Only after the steep early pubertal increase in LH, ovarian steroidogenesis is activated, with increases in androgen and estrogen secretion. Under further FSH stimulation, follicular growth and maturation proceed. The first menstrual cycles are mostly anovulatory for 1 to 2 years. Luteal phase insufficiency is common the first five years after menarche.

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Hypothalamo-pituitary-gonadal axis in control of female reproductive cycleIndian J Physiol Pharmacol. 2001

Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is pivotal to the regulation of reproductive physiology in vertebrates. The characteristic periodic secretion of gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus (MBH), at the rate of one pulse an hour is essential for the maintenance of the menstrual cycle. These pulses are due to oscillations in the electrical activity of the GnRH pulse generator in the MBH.

The GnRH pulse generator is under the influence of an assortment of interactions of multiple neural, hormonal and environmental inputs to the hypothalamus. Hence, a number of conditions such as stress, drug intake, exercise, sleep affect the activity of this pulse generator.

Any deviation of normal frequency results in disruption of normal cycle. The cycle can become anovulatory in the hypothalamic lesions

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Influence of the ovarian cycle on the central nervous system – Ther Umsch. 2002

In general, estradiol and testosterone exert a stimulatory, progesterone an inhibitory effect on neuronal activities which are mediated by excitatory (e.g. glutamate, aspartate), and inhibitory amino acids (e.g. GABA) and neuropeptides (e.g. beta-endorphin), respectively.

The pulse amplitudes are primarily influenced by estradiol, but neuropeptide Y, neurotensin and noradrenaline contribute to their preovulatory enhancement.

Despite of this, up to 20% of ovulatory cycles do not show any rise in body temperature.

It could be demonstrated that performance on tests of articulatory and fine motor skills are enhanced in the late follicular phase as compared to the menstruation phase, while spatial ability was better during menses. Estrogens may influence mood and well-being in a favorable manner, while in predisposed women progesterone may cause symptoms of premenstrual syndrome.

Somatic complaints (back pain, abdominal pain, breast tenderness) which are highest before and during menstruation, are probably associated with a lowered pain threshold due to a fall in the beta-endorphin levels in the CNS.

FOR A 2012 UPDATE SEE https://biozhena.wordpress.com/2012/05/28/what-is-the-mechanism-of-stress-and-how-does-it-affect-reproduction-an-update/

Stress and fertility

December 22, 2007

How stress affects the inherently narrow fertile window

Stress can do unwanted things to a woman and her menstrual cycle. In a nutshell, stress can make a woman completely infertile in this menstrual cycle (e.g., LPD, see below), or it can change the position of her fertile window (the time of ovulation included) within the menstrual cycle. Any of this can cause problems and lead to more stress…

The medical term is stress response, and it refers to the overall reaction of the organism to any adverse stimulus, whether it be of physical, mental or emotional kind, internal or external. The purpose is to adapt to challenge, and this goes on all the time. (C’est la vie! Real life is a never-ending series of stress responses.) Should the compensating reaction of the organism be inadequate or inappropriate, a pathological disorder may result.

The HPA axis, the immune system and the sympathetic nervous system are involved in the stress response. Don’t get stressed by some undecipherable abbreviations or unknown words — look up The Alphabet of bioZhena, you may find it or them in there!

Just remember, this is no Alphabet of Ben Sira!

( /2007/11/28/the-alphabet-of-biozhena/)

021r from The Book of Urizen

Stress and the menstrual cycle

It is a matter of conventional wisdom that perturbations in the external or internal environments – that is stress – can interfere with the normal course of the menstrual cycle. To further quote the expert, disturbances in the menstrual cycle occur in response to exercise and physical demands, stress and emotional demands, and diet and nutritional demands [citation below, ref. 17].

As Michel J. Ferin writes, with reference to the brain component of the female reproductive control system, “with minimal reduction in (GnRH) pulse frequency, small undetected defects in the follicular maturation process may occur, whereas with a higher degree of pulse inhibition the follicular phase may be prolonged, and luteal phase deficiency, anovulation, and amenorrhea may develop.”

A micro-glossary: The follicular maturation process is also called folliculogenesis. GnRH is a brain-produced hormone involved in folliculogenesis. A maturing follicle is a small, protective sac, gland, or cluster of cells in the ovary, in which an egg (ovum) develops towards ovulation, in order to have a chance to be fertilized. For visualization see http://images.google.com/images?hl=en&q=ovarian+follicles&btnG=Search+Images&gbv=2

https://biozhena.files.wordpress.com/2007/12/what-is-stress.pdf is an ad hoc selection of a few abstracts from my files on psychoneuroimmunoendocrinology papers addressing ovulation, reproduction and folliculogenesis.

Stress and the Ovulona

Results obtained with our Ovulona prototypes lead to the conclusion that the technique appears to detect such phenomena as referred to by Dr. Ferin. This is not so much or merely the different rates of follicular maturation in different menstrual cycles, but more seriously the delayed ovulations in those cycles where it takes longer than 1 day to reach the ovulation marker trough (minimum), as observed in some non-baseline subjects’ cyclic profiles.

This is the detection of Ferin’s “minimal reduction in (GnRH) pulse frequency, small undetected defects in the follicular maturation process may occur”. Whereas, “with a higher degree of pulse inhibition the follicular phase may be prolonged, and luteal phase deficiency [LPD], anovulation, and amenorrhea may develop” – and, indeed, we have seen the LPD, the extended follicular phase and short luteal phase, and various other aberrations in the cyclic profiles of different women over the years.

bioZhena is basically involved with non-pathological stress responses through monitoring certain end-organ effects.

Abnormal cyclic patterns of the end-organ effects may serve as an early warning of pathological disorders. This remains to be systematically investigated. Anecdotal evidence in non-baseline cyclic profiles is compelling.

For a hint of this, refer to these 5 slides: Five slides selected for bioZhena weblog

The non-baseline cyclic profiles present certain quantitative deviations from baseline: e.g., their post-ovulation (luteal) phase can be not of the normal length of about 14 days (12 to 16). In such abnormal cycles with short luteal phases (<11 days), observed more often in older women, there is a lack of synchrony due to a luteal-phase mismatch between the ovarian steroids and the pituitary peptides [S.K. Smith et al., J. Reprod. Fert. 75:363, 1985].

Here is an example of a non-baseline cyclic profile of a woman with a short luteal phase (8 days); for comparison, the woman’s BBT profile in the same cycle is also shown:

Short luteal phase cyclic profile

A woman’s history of amenorrhea and/or of ovarian cysts is pertinent to the case of abnormally short luteal phase, but so is stress and its effect on the GnRH hormone generator in the hypothalamus of the brain, which affects the output of the pituitary peptides.

For example, it is known in a general way that norepinephrine and possibly epinephrine in the hypothalamus increase the GnRH pulse frequency. Conversely, the endogeneous opioid peptides, the enkephalins and beta-endorphin, reduce the frequency of the GnRH pulses. These interactions are particularly important at the time of the “mid-cycle” LH surge, affecting its timing and intensity [W.F. Ganong, Review of Medical Physiology, 17th edition, Appleton & Lange, 1995, Chapter 23].

The slow rate of descent of the Ovulona signal – seen in slides 1 and 2, above – from the short-term predictive peak to the ovulation marker trough (minimum) is a useful diagnostic feature that is indicative of an extended period of time required for the two “clocks” (the circhoral and the circamensual) to become synchronized as a precondition of ovulation.

Activation of the hypothalamus-pituitary-adrenal (HPA)-axis by physical, chemical, and psychological perturbations is known to result in elevated levels of serum corticosteroid hormones. Corticosteroids are the principal effectors in the stress response and are thought to be responsible for both adaptational and maladaptational response to perturbing situations. They have profound effects on mood and behavior, and affect neurochemical transmission and neuroendocrine control.

Stress double whammy

Cortisol, the predominant corticosteroid in primates, is often regarded as the “stress hormone” and consequently serves as a marker of stress. Cortisol can be measured in blood, urine, and saliva. For information about the adrenal gland and stress, go to http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/adrenal/index.html .

We logically mentioned stress in the post on Sub-fertility (or Reduced Fertility), in the following reminder. The endocrinologist professor Brown may be quoted:

“Failing to conceive when wanted is stressful and therefore favours infertility. It should be remembered that, apart from a few conditions such as blocked fallopian tubes, absent sperm and continued anovulation, most couples will conceive eventually without help. However, the modern expectation is one of immediate results, and the main function of assisted reproduction techniques is therefore to shorten the waiting time for conception.”

To which we would add that bioZhena aims to offer a more affordable and safer alternative to the A.R.T. approach.

References as excerpted from our White Paper:

[17] Michel J. Ferin, “The menstrual cycle: An integrative view”, Chapter 6 in [2], pages 103 – 121.

[2] Eli Y. Adashi, John A. Rock, and Zev Rosenwaks, editors, “Reproductive Endocrinology, Surgery, and Technology”, Lippincott – Raven, 1996.

Terminology reminder:

Luteal phase is the phase after ovulation. Follicular phase is the phase before ovulation. Referencing the phases of the menstrual cycle. Amenorrhea = abnormal absence of menstrual bleeding. GnRH = gonadotropin releasing hormone. See The Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/


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