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2 Stress Is the Main Cause of Folliculo-Luteal Insufficiency

2 Stress Is the Main Cause of Folliculo-Luteal Insufficiency

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34



3



%



p < 0.001



Aetiology and Pathomechanism of Folliculo-Luteal Insufficiency



p < 0.001



p < 0.001



p < 0.001



p < 0.001



250

200

150

100

50

0

progesterone



%



p < 0.001



weight



BMI



p < 0.001



p < 0.001



prolactin



cortisol



p < 0.001



p < 0.01



250

200

150

100

50

0

Testosterone



TEBG



Free testost. Androstenedione



100% : Phisiological control group (n=100)



DHEA-S



Folliculo-luteal insufficiency (n=419)



Fig. 3.1 Hormonal and clinical characteristics of folliculo-luteal insufficiency



Table 3.1 Clinical and hormonal characteristics of folliculo-luteal insufficiency (FLI) with and

without hyperandrogenism (HAN)

Physiological

FLF

N = 100,

mean ± SD

Age (years)

Weight (kg)

BMI (kg/m2)

Progesterone (ng/ml)

(nmol/l)

Prolactin (mIU/l)

Cortisol (nmol/l)

Testosterone (nmol/l)

SHBG (nmol/l)

Free testost. (pmol/l)

Androstenedione

(nmol/l)

DHEA-S (μmol/l)



Significance



29.6 ± 3.4

55.2 ± 5.3

20.7 ± 1.4

21.2 ± 2.1

67.4 ± 6.7

237 ± 105

317 ± 47

1.82 ± 0.41

131 ± 39

23.9 ± 4.65

5.37 ± 1.43



NS

p < 0.001

p < 0.001

p < 0.001



3.97 ± 1.31



FLI without

HAN

N = 368

mean ± SD



Significance



FLI with

HAN

N = 51

mean ± SD



NS

p < 0.001

p < 0.001

P < 0.05



p < 0.001

p < 0.001

NS

NS

NS

p < 0.05



29.4 ± 4.3

59.5 ± 9.0

22.2 ± 1.5

10.8 ± 3.5

34.3 ± 11.1

500 ± 416

375 ± 113

1.88 ± 0.69

124 ± 57

25.3 ± 11.5

6.18 ± 2.79



NS

p < 0.01

p< 0.001

p < 0.001

p < 0.001

p < 0.001



28.6 ± 3.5

64.5 ± 14.6

23.7 ± 1.5

9.8 ± 3.8

31.2 ± 21.1

446 ± 359

436 ± 119

3.10 ± 1.02

70 ± 34

81.2 ± 52.7

9.35 ± 3.49



NS



4.02 ± 1.87



p < 0.001



6.00 ± 3.07



3.2



Stress Is the Main Cause of Folliculo-Luteal Insufficiency



35



Hyperandrogenism (HAN) was present in 12.2 % of the patients (mainly hirsutism

and elevated serum androgen values, especially elevated free testosterone levels).

The levels of serum cortisol and prolactin were significantly higher (p < 0.001) in

FLI than in the physiologic control group. Cortisol levels exceeded the 415 nmol/l

(150 ng/ml) value (average + 2SD) in 39.5 % of the patients, which is generally

accepted as the physiological limit (Abraham 1981) and also measured in our physiologic control group. Serum prolactin levels were elevated in 24.8 % of the patients

(over 640 mIU/l; Soules et al. 1991) and were over the 447 mIU/l upper limit found

in our physiological control group in 38.1 % cases (average + SD).

The levels of tested serum androgens – testosterone, free testosterone, androstenedione and DHEA-S – were also significantly higher (p < 0.001) compared to

the physiological values measured in the control group, while the level of SHBG

was significantly (p < 0.001) lower than the physiological range (Fig. 3.1 and

Table 3.1). When we separately analysed the androgen levels of the 51 patients

(12.2 %) suffering from HAN, they were significantly (p < 0.001) higher than those

measured in the patients without HAN (87.8 %). In the latter, every androgen level –

except for androstenedione – was physiological and did not differ from the corresponding value of the control group: the elevated level of serum androgens in FLI

can be attributed to the high levels of patient suffering from HAN. The weight and

BMI of patients with HAN were significantly (p < 0.001) elevated compared both to

the physiologic control group and to the patient group without HAN. Cortisol and

prolactin levels in FLI without HAN were also significantly higher (p < 0.001) than

the physiological (Table 3.1).

The causal role of stress and HPA axis hyperfunction and the above presented

explanation of the pathogenesis of FLI can be demonstrated if the corticoid suppression of HPA axis results in normalisation or amelioration of luteal function.

Dexamethasone (DEX) treatment decreases the secretion of cortisol, ACTH and

CRH, while on the other hand, it mostly replaces the effect of the missing cortisol.

As the secretion of adrenal androgens depends on the ACTH-cortisol feedback and

does not have a regulation of its own, DEX treatment decreases the amount of adrenal androgens and oestrogens converted from them and thus their adverse central

and ovarian effects. Because of this, we examined the hormonal and clinical effects

of low-dosage DEX treatment in FLI. We used a DEX dosage that in itself does not

negatively affect the HPO system. We investigated the effect of DEX treatment on

luteal function both in FLI associated with HAN and in FLI without HAN. DEX

treatment – as the peak of cortisol secretion occurs early in the morning – was

applied continuously, with a 0.5 mg dosage administered every evening.

In FLI associated with HAN, the DEX treatment caused a significant (p < 0.001)

increase in the average P value that characterises luteal function, and it fell behind

the physiological value (over 17 ng/ml) only in two cases. The levels of cortisol and

every serum androgens decreased significantly (p < 0.001) as a result of DEX treatment. Serum level of prolactin also significantly (p < 0.05) decreased as an effect of

DEX treatment (Table 3.2).

In the cases of FLI without HAN, DEX treatment increased the average level of

P also significantly (p < 0.001) (from 12.7 to 21.4 ng/ml, average ± SD) and



3



36



Aetiology and Pathomechanism of Folliculo-Luteal Insufficiency



Table 3.2 Hormonal changes during dexamethasone treatment of folliculo-luteal insufficiency

associated with hyperandrogenism (0.5 mg every evening)



Progesterone ng/ml

nmol/l

Prolactin mIU/l

Cortisol (nmol/l)

Testosterone nmol/l

SHBG nmol/l

Free testost. pmol/l

Androstenedione nmol/l

DHEA-sulphate μmol/l



Basal value

average ± SD

N = 18



Dexamethasone treatment

average ± SD

N = 18



10.8 ± 2.9

34.3 ± 9.2

435 ± 318

430 ± 97

3.24 ± 1.02

69 ± 38

91.3 ± 62.8

10.85 ± 2.86

6.88 ± 1.69



21.0 ± 2.0

66.8 ± 6.3

234 ± 140

66 ± 30

1.11 ± 0.40

119 ± 50

28.4 ± 18.0

2.58 ± 0.97

1.31 ± 0.97



Significance

p < 0.001

p < 0.05

p < 0.001

p < 0.001

p < 0.001

p < 0.001

p < 0.001

p < 0.001



Table 3.3 Hormonal changes during dexamethasone treatment of folliculo-luteal insufficiency

without hyperandrogenism (0.5 mg per evening)



Progesterone ng/ml

nmol/l

Prolactin mIU/l

Cortisol nmol/l

Testosterone nmol/l

SHBG nmol/l

Free testost. pmol/l

Androstenedione nmol/l

DHEA-sulphate μmol/l



Basal value

average ± SD

N = 17



Dexamethasone treatment

average ± SD

N = 17



12.7 ± 2.8

40.4 ± 8.9

425 ± 278

465 ± 112

1.92 ± 0.47

127 ± 46,7

26.0 ± 4.2

6.11 ± 2.70

4.03 ± 1.85



21.4 ± 3.5

68.1 ± 11.1

227 ± 135

57 ± 25

0.91 ± 0.24

111 ± 43

13.6 ± 3.2

2.48 ± 0.77

0.61 ± 0.35



Significance

p < 0.001

p < 0.05

p < 0.001

p < 0.001

NS

p < 0.001

p < 0.001

p < 0.001



decreased the levels of cortisol and every examined serum androgens. DEX caused

a significant (p < 0.05) decrease also in the prolactin serum levels of this study group

(Table 3.3).



3.3



Discussion



The role of stress in hypothalamic amenorrhoeal conditions has been proven by

several authors (Monzani et al. 1989; Biller et al. 1990; Nappi et al. 1993; Vrekoussis

et al. 2010). Depending on the level of stress, FLI is a transition between the physiological cycle and anovulation (Wildt et al. 1993; Genazzani et al. 1995a, b;

Kalantaridou et al. 2010; Vrekoussis et al. 2010).

The inevitable consequence of the stress-induced elevation of CRH (corticotropin-releasing hormone) secretion, via the increased ACTH secretion, is the



3.3



Discussion



37



secretion of cortisol and the enhanced function of the adrenal cortex. Increased

levels of cortisol can also be demonstrated in cycle abnormalities caused by physical exertion, extreme weight loss, low or high body weight for extended periods and

anorexia nervosa and in amenorrhoea as well (Schweiger 1991; Warren 1992;

Whirladge and Cidlowski 2013). A likewise elevated cortisol level can be measured

in other hypothalamic amenorrhoeic conditions as well (Armenau et al. 1992; Nappi

et al. 1993), which seems to support the view that a common pathomechanism lies

behind the cycle abnormalities mentioned above. The exerted negative effect of

elevated cortisol level on the hypophysis and directly on folliculogenesis is reported

by many authors (Monzani et al. 1989; Whirladge and Cidlowsky 2010, 2013).

The increased activity of the adrenal cortex caused by the effects of CRH and

ACTH also increases androgen secretion, especially in severe and chronic stress. At

the same time, enhanced androgen secretion negatively affects reproductive function through its suppressing effect on GnRH secretion and the hypophysis as well as

its direct effect on folliculogenesis (Veldhuis 1990) and also through the increased

peripheral oestrogen synthesis (Graf et al. 1993).

A part of the androgens is converted to oestrogens on the periphery, primarily to

the oestrone called androstenedione, which physiologically gives 1.3 % of the total

androstenedione. The rate of conversion increases in parallel with being overweight

and age (Edman and MacDonald 1976; MacDonald et al. 1978; Siiteri 1981).

Increased adrenal androgen secretion thus causes an elevated extraovarian oestrogen production that is even further increased by the raised conversion rate in overweight patients. The important effect of oestrone generated by the above-mentioned

processes is well demonstrated by that its biological effectivity is one-third, while

its free plasma concentration is three times larger compared to that of oestradiol.

Oestrogens formed on the periphery can disturb the menstrual cycle through several

mechanisms: via affecting GnRH and gonadotropin secretion as well as by direct

ovarian effect.

The effect on the hypophysis appears to be the most important of these. To our

current understanding, different levels and ratios of LH and FSH secretion developed under the same GnRH effect are determined by the level of steroids affecting

primarily the hypophysis, especially oestrogen, although other steroids play a considerable role as well. Higher oestrogen level increases LH secretion and decreases

FSH secretion. If the oestrogen effect is of extraovarian origin, the elevated LH/FSH

ratio is present from the beginning of the cycle. Low FSH levels lead to disturbed

folliculogenesis, while untimely and elevated LH secretion causes multiplication

decrease and luteinisation of granulosa cells prematurely. Moreover, untimely

occurrence of the LH peak causes the first meiotic division of the egg cell to terminate too early and thus the ovulation of a physiologically aged egg cell (Watson

et al. 1993; Shohan et al. 1993). Furthermore, increased LH levels enhance the

androgen secretion of ovarian parts that can produce androgens (theca cells, stroma

cells, hilus cells). Besides their direct hypothalamic and ovarian effect, androgens

decrease the LH and FSH secretion of the hypophysis at the same time and the luteal

phase is shortened depending on testosterone levels (Smith et al. 1979), which can

be reproduced by administering exogenous androgens (Gooren 1985). While these



38



3



Aetiology and Pathomechanism of Folliculo-Luteal Insufficiency



circumstances appear more pronouncedly in case of anovulatory cycle and

hypothalamic amenorrhoea, they are less severe in FLI and ovulation still takes

place but, through the mechanisms described above the hormonal abnormality of

the menstrual cycle, FLI develops.

Many authors reported the above-mentioned hormonal changes in FLI. Several

authors detected elevated beta-endorphin (Shaarawy et al. 1991) and serum androgen

(Tulppala et al. 1993; Watson et al. 1993) in FLI. Other researchers found elevated

oestrogen excretion (Watson et al. 1993), decreased FSH levels and increased LH/FSH

rate (Sherman and Korenman 1974; DiZerega and Hodgen 1981; Cook et al. 1983;

Smith et al. 1979; Azziz 1996) in the follicular phase of cycles with FLI. Elevated free

testosterone, DHEA-S and oestrone levels were found in obese patients (Azziz et al.

1991), and in addition, the 24-h cortisol excretion and the ACTH and cortisol secretion

are also significantly increased in obesity (Pasquali and Casimirri 1993). In overweight

patients (BMI ≥30), the prevalence of ovulatory infertility is 2.1-fold to that of normal

weight patients, and in the case of low body weight, functional infertility occurs 4.7

times more frequently (Green et al. 1988; Cupisti et al. 2007).

Our studies also support the above presented pathomechanism of the development of FLI. The primary causal role of stress in FLI is verified by the significantly

(p < 0.001) elevated levels of cortisol, prolactin and androgen. In FLI associated

with HAN, the serum levels of cortisol and exclusively adrenal DHEA-S are significantly (p < 0.01–0.001) elevated compared to patients without HAN, which seems

to support the causal role of increased and presumably chronic stress in the development of adrenal HAN.

On the average, absolute weight of patients suffering from FLI was 5.1 kg (8.4 %)

higher than in the control group, and 19.8 % of patients were overweight. Increased

body weight in itself causes elevated secretion of CRH and ACTH through increased

peripheral cortisol use, even with normal cortisol levels, but in obesity we have to

take into account the hyperactivity of the HPA axis (Pasquali and Casimirri 1993;

Weaver et al. 1993). The elevated level of cortisol decreases gonadotropin secretion

through an indirect hypophyseal effect as well (Monzani et al. 1989; Hayashi and

Moberg 1990). Adrenal androgen secretion increases (Loughlin et al. 1985), which

alone can lead to elevated peripheral oestrogen (especially oestrone) production

(Graf et al. 1993). However, in obesity the peripheral androgen-oestrogen conversion rate increases in parallel with the excess weight (Edman and MacDonald 1976).

This further increases peripheral oestrogen production, which in turn results in disturbed folliculogenesis by reducing FSH and raising LH levels and increasing the

FSH and LH pulse frequency (Soules et al. 1987; Graf et al. 1993). From the aspect

of the pathogenesis of FLI associated with increased body weight, elevated adrenal

androgen secretion and peripheral oestrogen production play an important role

besides the direct hypothalamic effect of high CRH levels.

Serum hormone levels detected in FLI significantly differed from the physiological, but still fall behind the levels found by other researchers in anovulation, oligomenorrhoea or hypothalamic amenorrhoea. In hypothalamic amenorrhoea, the

baseline and 4-hour cortisol levels are 50–100 % higher than the physiological

(Biller et al. 1990; Nappi et al. 1993). In FLI we observed cortisol levels that were



3.3



Discussion



39



26 % higher than the average physiological level, which seems to support the view

that a common pathomechanisms underlies different cycle abnormalities, and at the

same time it shows that differences in the extents of various causal factors play a

determining role.

Favourable results were achieved when treating oligomenorrhoea, anovulatory

cycle, unstable cycle and FLI with the administration of opioid antagonists, which

inhibit the effect of increased CRH secretion on GnRH production (Wildt et al.

1993; Genazzani et al. 1995a, b). Apart from the suppression of HPA axis function,

the diminution of peripheral effects (adrenal function, peripheral androgen-oestrogen conversion) will theoretically lead to even better therapeutic results. The positive therapeutic outcomes of treating FLI with or without hyperandrogenism with

DEX alone and the beneficial adjuvant effect of DEX in CC-resistant cases (see

later) support this view. At the same time it seems to confirm the primary causal role

of stress in the development of FLI.

Serum prolactin level decreases nearly by its half by DEX treatment of FLI cases

both with HAN and without HAN, which suggests that elevated prolactin levels

only play a secondary role in FLI and are rather a consequence of the increased

CRH secretion than a primary causal factor as in hyperprolactinaemic amenorrhoea

(Lox and Pau 1993; Tay et al. 1993). This is further demonstrated by the studies of

Glazener et al. (1987), who observed the same frequency of spontaneous conception

both with physiological and increased prolactin levels in 1-year ovulatory infertility

cases. Many authors debate the primary causal role of prolactin in FLI (Glazener

et al. 1987; Soules et al. 1991). The poor therapeutic results of bromergocriptine

treatment also imply the secondary role of prolactin in FLI. The currently accepted

view is that in case of cyclic menstruation and ovulation, checking prolactin level is

unnecessary (ESHRE 1996; RCOG 2004; Stratford et al. 1999).

Several authors achieved a positive effect using CC treatment completed with

DEX, especially in anovulation and PCOS (Lobo et al. 1982; Daly et al. 1984; Trott

et al. 1996; Elnashar et al. 2006). After reviewing the literature, completing CC

treatment with DEX seemed remarkably favourable compared to CC treatment

alone (OR 9.46) in PCOS and in amenorrhoeas without PCOS as well (Brown et al.

2009/Cochrane database). Moradan and Ghorbani (2009) achieved significantly

better pregnancy rates in unexplained infertility by combined CC + DEX treatment

than with CC treatment alone.

On a representative patient population, our studies show that stress plays a central role in the pathogenesis of FLI, on one hand through the increased CRH secretion that acts via a direct central mechanism and, on the other hand, through the

enhanced adrenal activity (cortisol, adrenal androgens, increased peripheral oestron

production). The pathomechanism of FLI induced by increased body weight is similar (increased HPA activity), although the causal role of peripheral effects is likely

more pronounced here.

The various stress factors collectively referred to as psychosocial stress may

explain the considerable variability of the whole menstrual cycle (FLF) (Crosignani

1988; Davis et al. 1989; Jones 1991). The effect of everyday stressors is obviously

determined by personality traits. The wide range of temporal, short-termed stress



40



3



Aetiology and Pathomechanism of Folliculo-Luteal Insufficiency



situations and chronic stress states with varying intensity can both explain how FLI

can be so variable and occur both temporarily and chronically. However, it seems

that the more chronic a stress state (or body weight deviation) is, the lower the

chance of complete FLF normalisation is (see later). In our studies we found that the

outcome of pregnancy is essentially determined by the hormonal relations (FLF) of

the conception cycle (see later). Based on the above, short, temporary stress can be

the cause of sporadic abortions, shorter or longer periods of infertility, preterm

birth, IUGR, etc. Chronic, continuous and high stress can underlie unexplained

infertility. Habitual abortion might be caused by chronic stress with varying intensity, where apart from abortion, preterm birth and IUGR are significantly more

prevalent and infertility periods between pregnancies occur more frequently. We

suppose that the variability of cycles accounts for the general abundancy of different forms of unfavourable pregnancy outcomes: according to national statistics,

spontaneous clinical abortion occurs in 15.1 %, preterm birth in 9.5 %, IUGR in

10.1 % and preeclampsia in 3–5 %, which altogether affect 38–40 % of desired pregnancies in Hungary.



References

Abraham GE. Adrenal androgens in hirsutism. In: Genazzani AR, Thijssen JHH, Siiteri PK, editors. Adrenal androgens. New York: Raven Press; 1981. p. 267–82.

Andrews FM, Abbey A, Halman LJ. Is fertility-problem stress different? The dynamics of stress in

fertile and infertile couples. Fertil Steril. 1992;57:1247–53.

Armeanu MC, Berkhout GM, Schoemaker J. Pulsatile luteinizing hormone secretion in hypothalamic amenorrhea, anorexia nervosa, and polycystic ovarian disease during naltrexone treatment. Fertil Steril. 1992;57:762–70.

Azziz R, Bradley EL, Zacur HA, Boots LR, Parker CR. Effect of obesity on the response to acute

adrenocorticotropin stimulation in eumenorrheic women. Fertil Steril. 1991;56:427–34.

Azziz R. The adrenal connection. In: Adashi EY, Rock JA, Rosenwaks Z, editors. Reproductive endocrinology, surgery and technology. Philadelphia: Lippincott-Raven Publ; 1996. p. 1161–80.

Balasch J, Vanrell JA. Corpus luteum insufficiency and fertility: a matter of controversy. Hum

Reprod. 1987;2:557–67.

Balasch J, Jove IC, Marquez M, Vanrell JA. Early follicular phase follicle stimulating hormone

treatment of endometrial luteal phase deficiency. Fertil Steril 1990;54:1004–7.

Biller BMK, Federoff HJ, Koenig JI, Klibanski A. Abnormal cortisol secretion and responses to

corticotropin-releasing hormone in women with hypothalamic amenorrhea. J Clin Endocrinol

Metab. 1990;70:311–7.

Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E. Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009;(4):CD002249.

Check JH, Goldberg BB, Kurtz A, Adelson HG, Rankin A. Pelvic sonography to help determine

the appropriate therapy for luteal phase defects. Int J Fertil. 1984;29:156–8.

Check JH, Nowroozi K, Choe J, Lurie D, Dietterich C. The effect of endometrial thickness and

echo pattern on invitro fertilization outcome in donor oocyte embryo transfer cycle. Fertil Steril

1993;59:72–5.

Cook CB, Nippoldt TB, Kletter GB, Kelch RP, Marshall JC. Naloxone increases the frequency of

pulsatile luteinizing hormone secretion in women with hyperprolactinemia. J Clin Endocrinol

Metab. 1991;73:1099–105.



References



41



Cook CL, Rao CV, Yussman MA. Plasma gonadotropin and sex steroid hormone levels during

early, midfollicular, and midluteal phases of women with luteal phase defects. Fertil Steril

1983;40:45–8.

Crosignani PG. The defective luteal phase. Hum Reprod. 1988;3:157–60.

Cupisti S, Dittrich R, Binder H, Kajaia N, Hoffmann I, Maltaris T, Beckmann MW, Mueller A.

Influence of body mass index on measured and calculated androgen parameters in adult women

with Hirsutism and PCOS. Exp Clin Endocrinol Diabetes. 2007;115(6):380–6.

Dallenbach-Hellweg G. The endometrium of infertility. A review. Pathol Res Pract. 1984;178:527–37.

Daly DC, Walters CA, Soto-Albors CE, Tohan N, Riddick DH. A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertil Steril. 1984;41:844–8.

Davis OK, Berkeley AS, Naus GJ, Cholst IN, Freedman KS. The incidence of luteal phase defect in

normal, fertile women, determined by serial endometrial biopsies. Fertil Steril. 1989;51:582–6.

Deichert U, Hackeloer BJ, Daume E. The sonographic and endocrinologic evaluation of the endometrium in the luteal phase. Hum Reprod. 1986;1:219–22.

Dickey RP, Olar TT, Curole DN, Taylor SN, Rye PH. Endometrial pattern and thickness associated

with pregnancy outcome after assisted reproduction technologies. Hum Reprod. 1992;7:418–21.

Dickey RP, Olar TT, Taylor SN, Curole DN, Matulich EM. Relationship of endometrial thickness

and pattern to fecundity in ovulation induction cycles – effect of clomiphene citrate alone and

with human menopausal gonadotropin. Fertil Steril. 1993;59:756–60.

Dickey RP, Holtkamp DE. Development, pharmacology and clinical experience with clomiphene

citrate. Hum Reprod Update. 1996;62:483–506.

DiZerega GS, Hodgen GD. Follicular phase treatment of luteal phase dysfunction. Fertil Steril.

1981;35:428–32.

Domar AD, Zuttermeister PC, Seibel M, Benson H. Psychological improvement in infertile women

after behavioral treatment – a replication. Fertil Steril. 1992;58:144–7.

Edman CD, MacDonald PC. The role of extraglandular estrogen in women in health and disease.

In: James VHT, Serio M, Giusti G, editors. The endocrine function of the human ovary.

London/New York/San Francisco: Academic Press; 1976. p. 135–51.

Elias AN, Wilson AF. Exercise and gonadal function. Hum Reprod 1993;8:1747–61.

Elnashar A, Abdelmageed E, Fayed M, Sharaf M. Clomiphene citrate and dexamethazone in

treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebocontrolled study. Hum Reprod. 2006;21:1805–8.

ESHRE. Guidelines to the prevalence, diagnosis, treatment and management of infertility. Hum

Reprod. 1996;1996(11):1775–807.

Geisthövel F, Skubsch U, Zabel G, Schillinger H, Breckwoldt M. Ultrasonographic and hormonal

studies in physiologic and insufficient menstrual cycles. Fertil Steril. 1993;39:277–83.

Genazzani AD, Gastaldi M, Petraglia F, Battaglia C, Surico N, Volpe A, Genazzani AR. Naltrexone

administration modulates the neuroendocrine control of luteinizing hormone secretion in hypothalamic amenorrhoea. Hum Reprod. 1995a;10:2868–71.

Genazzani AD, Petraglia F, Gastaldi M, Volpogni C, Gamba O, Genazzani AR. Naltrexone treatment restores menstrual cycles in patients with weight loss-related amenorrhea. Fertil Steril.

1995b;64(5):951–6.

Glazener CM, Kelly NJ, Hull MG. Prolactin measurement in the investigation of infertility in

women with a normal menstrual cycle. Br J Obstet Gynaecol. 1987;94:535–8.

Goldstein D, Zuckerman H, Harpaz S, Barkai J, Geva A, Gordon S, Shalev E, Schwartz M.

Correlation between estradiol and progesterone in cycles with luteal phase deficiency. Fertil

Steril. 1982;37:348–54.

Gooren LJ. Exogenous androgens decrease the length of the luteal phase and increase the length of

the follicular phase. Horm Metab Res. 1985;17:683–4.

Graf MA, Bielfeld P, Distler W, Weiers C, Kuhnvelten WN. Pulsatile luteinizing hormone secretion

pattern in hyperandrogenemic women. Fertil Steril. 1993;59:761–7.

Green BB, Weiss NS, Daling JR. Risk of ovulatory infertility in relation to body weight. Fertil

Steril. 1988;50:721–6.



42



3



Aetiology and Pathomechanism of Folliculo-Luteal Insufficiency



Hamilton MP, Fleming R, Coutts JR, MacNaughton MC, Whitfield CR. Luteal phase deficiency:

ultrasonic and biochemical insights into pathogenesis. Br J Obstet Gynaecol 1990;97:569–75.

Hayashi KT, Moberg GP. Influence of the hypothalamic pituitary adrenal axis on the menstrual

cycle and the pituitary responsiveness to estradiol in the female rhesus monkey (Macaca

mulatta). Biol Reprod. 1990;42:260–5.

Jones GS, Acosta AA, Garcia JE, Bernardus RE, Rosenwaks Z. The effect of follicle-stimulating

hormone without additional luteinizing hormone on follicular stimulation and oocyte

development in normal ovulatory women. Fertil Steril. 1985;43:696–702.

Jones GS, Garcia JE, Rosenwaks Z. The role of pituitary gonadotropins in follicular stimulation

and oocyte maturation in the human. J Clin Endocrinol Metab 1984;59:178–80.

Jones GS. Luteal phase defect: a review of pathophysiology. Curr Opin Obstet Gynecol.

1991;3:641–8.

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

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

Immunol. 2010;85:33–9.

Kehoe L, Parman R, Janik J, Callahan P. Opiate receptor subtype involvement in the stimulation of

prolactin release by beta-endorphin in female rats. Neuroendocrinology. 1993;57:875–83.

Lobo RA, Paul W, March CM, Granger L, Kletzky OA. Clomiphene and dexamethasone in women

unresponsive to clomiphene alone. Obstet Gynecol. 1982;60:497–501.

Loughlin T, Cunningham SK, Culliton M, Smyth PP, Meagher DJ, McKenna TJ. Altered androstenedione and estrone dynamics associated with abnormal hormonal profiles in amenorrheic

subjects with weightloss or obesity. Fertil Steril. 1985;43:720–5.

Lox CD, Pau KYF. Beta-endorphin levels in women with elevated prolactin and following bromocriptine therapy. Gen Pharmacol. 1993;24:1231–3.

MacDonald PC, Edman CD, Hemsell DL, Porter JC, Siiteri PK. Effect of obesity on conversion of

plasma androstenedione to oestrone in postmenopausal women with and without endometrial

cancer. Am J Obstet Gynecol. 1978;130:448–54.

McNatty KP, Makris A, De Grazia C, Osathanondh R, Ryan KJ. The production of progesterone,

androgens and oestrogens by human granulosa cells in vitro and in vivo. J Steroid Biochem.

1979;11:775–9.

Messinis IE, Templeton AA. The importance of follicle-stimulating hormone increase for folliculogenesis. Hum Reprod. 1990;5:153–6.

Monzani A, Petraglia F, De Leo V, Fabbri G, D’Ambrogio G, Volpe A, Genazzani AR.

Glucocorticoids but not vasopressin or oxytocin inhibit luteinizing hormone secretion in

patients with psychogenic amenorrhea. Gynecol Endocrinol. 1989;3:55–62.

Moradan S, Ghorbani R. Dexamethasone in unexplained infertility. Saudi Med J. 2009;30:

1034–6.

Nappi RE, Petraglia F, Genazzani AD, Dambrogio G, Zara C, Genazzani AR. Hypothalamic amenorrhea – evidence for a central derangement of hypothalamic-pituitary-adrenal cortex axis

activity. Fertil Steril. 1993;59:571–6.

Pasquali R, Casimirri F. Review – the impact of obesity on hyperandrogenism and polycystic ovary

syndrome in premenopausal women. Clin Endocrinol (Oxf). 1993;39:1–16.

Pohler KG, Geary TW, Atkins JA, Perry GA, Jinks EM, Smith MF. Follicular determinants of

pregnancy establishment and maintenance. Cell Tissue Res. 2012;349:649–64.

RCOG 2004 - National Collaborating Centre for Women’s and Children’s Health (UK).

London (UK): Fertility: Assessment and Treatment for People with Fertility Problems.

RCOG Press; 2004.

Schweiger U, Laessle RG, Tuschl RJ, Broocks A, Krusche T, Pirke KM. Decreased follicular phase

gonadotropin secretion is associated with impaired estradiol and progesterone secretion during

the follicular and luteal phases in normally menstruating women. J Clin Endocrinol Metab.

1989;68:888–92.

Schweiger U. Menstrual function and luteal-phase deficiency in relation to weight changes and

dieting. Clin Obstet Gynecol. 1991;34:191–7.



References



43



Shaarawy M, Shaaban HA, Eid MM, Abdel-Aziz O. Plasma beta-endorphin level in cases of luteal

phase defect. Fertil Steril. 1991;56:248–53.

Shapiro H, Cowell C, Casper RF. The use of vaginal ultrasound for monitoring endometrial preparation in a donor oocyte program. Fertil Steril. 1993;59:1055–8.

Sherman BM, Korenman SG. Measurement of serum LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the inadequate luteal phase. J Clin Endocrinol Metab.

1974;39:145–9.

Shoham Z, Di Carlo C, Patel A, Conway GS, Jacobs HS. Is it possible to run a successful ovulation

induction program based solely on ultrasound monitoring? The importance of endometrial

measurements. Fertil Steril. 1991;56:836–41.

Shoham Z, Jacobs HS, Insler V. Luteinizing hormone – its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase. Fertil Steril. 1993;59:1153–61.

Siiteri PK. Extraglandular oestrogen formation and serum binding of oestradiol relationship to

cancer. J Endocrinol. 1981;89:119–26.

Siklósi G, Lintner F, Olajos F. Strong correlation between prolactin and cortisol as well as cortisol

and androgens in adrenal hyperandrogenism. Proc. of V. World Congress on Hum. Reprod,

Athens; 1986. p. 322–4.

Smith KD, Rodriguez-Rigau LJ, Tcholakian RK, Steinberger E. The relation between plasma testosterone levels and the lengths of phases of the menstrual cycle. Fertil Steril. 1979;32:403–7.

Soules MR. Luteal phase deficiency. Clin Obstet Gynecol 1991;34:123–26.

Soules MR, Bremner WJ, Steiner RA, Clifton DK. Prolactin secretion and corpus luteum function

in women with luteal phase deficiency. J Clin Endocrinol Metab. 1991;72:986–92.

Soules MR, Clifton DK, Bremner WJ, Steiner RA. Corpus luteum insufficiency induced by a rapid

gonadotropin releasing hormone induced gonadotropin secretion pattern in the follicular phase.

J Clin Endocrinol Metab1987; 65:457–64.

Stouffer RL. Corpus luteum function and dysfunction. Clin Obstet Gynecol 1990;33:668–89.

Stouffer RL, Hodgen GD. Induction of luteal phase defects in rhesus monkeys by follicular fluid

administration at the onset of the menstrual cycle. J Clin Endocrinol Metab. 1980;51:669–71.

Stouffer RL, Hodgen GD, Ottobre AC, Christian CD. Follicular fluid treatment during the follicular versus luteal phase of the menstrual cycle: effects on corpus luteum function. J Clin

Endocrinol Metab. 1984;58:1027–33.

Stratford GA, Barth JH, Rutherford AJ, Balen AH. Plasma prolactin measurement is not indicated

in women in the routine investigation of uncomplicated infertility. Hum Fertil (Camb).

1999;2(1):70–1.

Tay CCK, Glasier AF, Illingworth PJ, Baird DT. Abnormal 24 hour pattern of pulsatile luteinizing

hormone secretion and the response to naloxone in women with hyperprolactinaemic amenorrhoea. Clin Endocrinol 1993;39:599–606.

Trott EA, Plouffe Jr L, Hansen K, Hines R, Brann DW, Mahesh VB. Ovulation induction in clomiphene-resistant anovulatory women with normal dehydroepiandrosterone sulfate levels: beneficial effects of the addition of dexamethasone during the follicular phase. Fertil Steril.

1996;66:484–6.

Tulppala M, Stenman UH, Cacciatore B, Ylikorkala O. Polycystic ovaries and levels of gonadotrophins and androgens in recurrentmiscarriage: prospective study in 50 women. Br J Obstet

Gynaecol. 1993;100:348–52.

Veldhuis JD. The hypothalamic pulse generator. The reproductive core. Clin Obstet Gynecol.

1990;33:538–50.

Vrekoussis T, Kalantaridou SN, Mastorakos G, Zoumakis E, Makrigiannakis A, Syrrou M,

Lavasidis LG, Relakis K, Chrousos GP. The role of stress in female reproduction and pregnancy: an update. Ann N Y Acad Sci. 2010;1205:69–75.

Warren MP. Amenorrhea in endurance runners. Clinical review 40. J Clin Endocrinol Metab.

1992;75:1393–7.

Wasser SK, Sewall G, Soules MR. Psychosocial stress as a cause of infertility. Fertil Steril.

1993;59:685–9.



44



3



Aetiology and Pathomechanism of Folliculo-Luteal Insufficiency



Watson H, Kiddy DS, Hamiltonfairley D, Scanlon MJ, Barnard C, Collins WP, Bonney RC, Franks S.

Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage. Hum Reprod. 1993;8:829–33.

Weaver JU, Kopelman PG, Mcloughlin L, Forsling ML, Grossman A. Hyperactivity of the hypothalamo-pituitary-adrenal axis in obesity – a study of ACTH, AVP, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia. Clin Endocrinol (Oxf). 1993;39:345–50.

Whirledge S, Cidlowski JA. Glucocorticoids, stress, and fertility. Minerva Endocrinol. 2010;35:

109–25.

Whirledge S, Cidlowski JA. A role for glucocorticoids in stress-impaired reproduction: beyond the

hypothalamus and pituitary. Endocrinology. 2013;154:4450–68.

Wildt L, Leyendecker G, Sirpetermann T, Waibeltreber S. Treatment with naltrexone in hypothalamic ovarian failure – induction of ovulation and pregnancy. Hum Reprod. 1993;8:350–8.

Ying YK, Daly DC, Randolph JF, Soto Albors CE, Maier DB, Schmidt CL, Riddick DH.

Ultrasonographic monitoring of follicular growth for luteal phase defects. Fertil Steril.

1987;48:433–6.



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