effect of increased testosterone level on · pdf fileeffect of increased testosterone level on...

6
Key words: FSH–LH disorder, FSH/LH ratio, polycystic ovary syndrome, septate uterus, fertility SUMMARY Preliminary results obtained in women treated for infertility, who were divided into two groups with normal and increased testosterone level as measured in serum on the fourth day of their cycles, are presented. Study population included 50 women, 25 of them with normal and 25 with increased testosterone level. The aim of the study was to investigate the interaction of serum testosterone level with ultrasound finding of septate uterus (indicating minor uterus abnormality), ultrasound diagnosis of the presence or absence of polycystic ovary, hormonal parameters, and sponta- neous or stimulated pregnancies. Study results revealed ten (40%) women with normal testosterone to have pathologic levels of FSH, LH and FSH/LH ratio; nine (36%) had polycystic ovary syndrome; and seven (28%) had septate uterus. The results showed an increased rate of FSH/LH inversion, polycystic ovary syndrome and septate uterus in the group of women with elevated testosterone. Although performed in quite a small group of subjects, the aim of the study conducted at Nada Polyclinic in Po‘ega, Croatia, was to show the effect of testosterone on some disorders associated with fertility, and to suggest the possible infertility management spontaneously or by insemination at a polyclinic of this type. INTRODUCTION Testosterone is usually mentioned in gynecologic literature in connection with the polycystic ovary syndrome (PCOS) (1-5) or a PCOS-like syndrome as one of its indicators. In practice, however, such a disorder is noticed in a number of women in whom an increased level of testosterone has been established, otherwise without any other sign of ovary function disorder. That is why we decided to test the effect of serum testosterone level on other disorders of the woman’s genital system. Therefore, the aim of the study was to assess the following: ultrasound and hormone findings indicating the existence of polycystic ovary, or a disorder of the pituitary gland - ovary axis; ultrasound finding of septate uterus (indicating minor uterus abnormality) (6); and the beginning of spontaneous and stimulated pregnancies (with particular individual or other tested symptoms). 53 Diabetologia Croatica 33-2, 2004 1 Nada Polyclinic, Po‘ega, Croatia 2 School of Medicine, University of Zagreb, Zagreb, Croatia Preliminary Communication Received: April 15, 2004 Accepted: June 16, 2004 EFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S FERTILITY @arko Šperanda 1 , Zvonimir Papiæ 2

Upload: phamnhu

Post on 20-Mar-2018

224 views

Category:

Documents


6 download

TRANSCRIPT

Page 1: EFFECT OF INCREASED TESTOSTERONE LEVEL ON · PDF fileEFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S ... testosterone values used at respective ... Z. Papiæ / EFFECT OF INCREASED

Key words: FSH–LH disorder, FSH/LH ratio,

polycystic ovary syndrome, septate uterus, fertility

SUMMARY

Preliminary results obtained in women treated for

infertility, who were divided into two groups with

normal and increased testosterone level as measured in

serum on the fourth day of their cycles, are presented.

Study population included 50 women, 25 of them with

normal and 25 with increased testosterone level. The

aim of the study was to investigate the interaction of

serum testosterone level with ultrasound finding of

septate uterus (indicating minor uterus abnormality),

ultrasound diagnosis of the presence or absence of

polycystic ovary, hormonal parameters, and sponta-

neous or stimulated pregnancies. Study results

revealed ten (40%) women with normal testosterone to

have pathologic levels of FSH, LH and FSH/LH ratio;

nine (36%) had polycystic ovary syndrome; and seven

(28%) had septate uterus. The results showed an

increased rate of FSH/LH inversion, polycystic ovary

syndrome and septate uterus in the group of women

with elevated testosterone. Although performed in

quite a small group of subjects, the aim of the study

conducted at Nada Polyclinic in Po‘ega, Croatia, was to

show the effect of testosterone on some disorders

associated with fertility, and to suggest the possible

infertility management spontaneously or by

insemination at a polyclinic of this type.

INTRODUCTION

Testosterone is usually mentioned in gynecologic

literature in connection with the polycystic ovary

syndrome (PCOS) (1-5) or a PCOS-like syndrome as

one of its indicators. In practice, however, such a

disorder is noticed in a number of women in whom an

increased level of testosterone has been established,

otherwise without any other sign of ovary function

disorder.

That is why we decided to test the effect of serum

testosterone level on other disorders of the woman’s

genital system. Therefore, the aim of the study was to

assess the following:

• ultrasound and hormone findings indicating the

existence of polycystic ovary, or a disorder of the

pituitary gland - ovary axis;

• ultrasound finding of septate uterus (indicating

minor uterus abnormality) (6); and

• the beginning of spontaneous and stimulated

pregnancies (with particular individual or other

tested symptoms).

53Diabetologia Croatica 33-2, 2004

1 Nada Polyclinic, Po‘ega, Croatia2 School of Medicine, University of Zagreb, Zagreb, Croatia

Preliminary CommunicationReceived: April 15, 2004

Accepted: June 16, 2004

EFFECT OF INCREASED TESTOSTERONE LEVEL ON

WOMAN’S FERTILITY

@arko Šperanda1, Zvonimir Papiæ2

Page 2: EFFECT OF INCREASED TESTOSTERONE LEVEL ON · PDF fileEFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S ... testosterone values used at respective ... Z. Papiæ / EFFECT OF INCREASED

SUBJECTS AND METHODS

The study included 50 women in whom serum

testosterone level was measured on the fourth day of

the cycle. According to the results, they were divided

into two groups: group A including women with normal

serum testosterone level (n=25), and group B with

increased serum testosterone level (n=25). The

normal and increased testosterone level was

determined according to the upper reference

testosterone values used at respective laboratories.

The following parameters were observed in both

subject groups (7,8):

� increased serum LH level,

� FSH/LH inversion in serum,

� presence of one or more symptoms of polycystic

ovary established by ultrasound, and

� anovulation without any signs of polycystic ovary

established by ultrasound.

The following signs of PCOS were observed by

ultrasound:

� typical configuration of tiny microcystic structures

on the ovary periphery,

� enlarged ovary volume,

� presence of an increased amount or density of

stroma with characteristic arterial blood flow, and

� tunica albuginea ovarii thickness exceeding normal

by 50%.

The rate of septate uterus was observed in both group

A and group B (19). The disorder was found on several

ultrasound examinations, the septum being wider than

7 mm.

The subjects who had other infertility factors such as

severe husband’s oligoasthenospermia, obstructed

fallopian tubes, large myomas associated with uterus

cavum deviation, uterus abnormalities, and age over 40

were excluded from the study, considering that in our

institution only insemination is used (Fig. 1).

RESULTS

In group A consisting of women with normal serum

testosterone levels, there was no case of increased

serum LH level; FSH/LH inversion was found in 10

54

@. Šperanda, Z. Papiæ / EFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S FERTILITY

Figure 1. Frequency of other infertility factors in

patients excluded from further treatment at Nada

Polyclinic.

Figure 2. Testosterone, FSH and LH levels in group A

(n=25).

Page 3: EFFECT OF INCREASED TESTOSTERONE LEVEL ON · PDF fileEFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S ... testosterone values used at respective ... Z. Papiæ / EFFECT OF INCREASED

(40%) women, whereas the remaining 15 (60%) women

had normal FSH and LH level (Fig. 2). Three (12%)

women had PCO signs, while anovulation without PCO

signs was not found. Septate uterus was found in three

(12%) women (Fig. 3). Other infertility factors were

recorded in 11 (44%) women who did not undergo

infertility treatment. Fourteen (56%) women with

normal testosterone level underwent treatment and

eight of them (32%) got pregnant (Fig. 4).

Analysis of successful pregnancies in group A women

(Fig. 5) reveals that pregnancy failed to occur in

subjects with FSH/LH inversion or PCOS. Appropriate

therapy resulted in pregnancy in one (4%) woman with

PCOS-like syndrome, five (20%) got pregnant

spontaneously, and three (12%) conceived with the

help of homoinsemination.

In group B including women with elevated serum

testosterone levels, FSH/LH findings were not

obtained in four (16%) subjects; FSH/LH inversion or

increased serum LH level was found in 13 (52%)

subjects (Fig. 2); PCOS was found in nine (36%) (Fig.

6), and anovulation in two (8%) subjects. Thus,

ultrasound revealed impaired ovary appearance in 11

(44%) women (Fig. 3). Septate uterus was found in

seven (28%) women, all with impaired FSH/LH ratio

(Fig. 3). Other infertility factors were identified in 15

(60%) women (Fig. 6), and ten (40%) of them

underwent treatment for infertility. Five (20%) women

got pregnant: three of them (12%) conceived

spontaneously (Fig. 7), one (4%) woman conceived by

homoinsemination and another one (4%) by IVF

procedure at another institution, as the procedure is

not performed at this polyclinic.

55Diabetologia Croatica 33-2, 2004

@. Šperanda, Z. Papiæ / EFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S FERTILITY

Figure 3. Serum testosterone, and rate of polycystic

ovary syndrome frequency and septate uterus on

ultrasound examination in groups A and B.

Figure 4. Success of infertility treatment in women

with normal serum testosterone level, group A

(n=25).

Figure 5. Conception profile in group A (n=25).

Figure 6. Successful pregnancies in group B (n= 25).

Page 4: EFFECT OF INCREASED TESTOSTERONE LEVEL ON · PDF fileEFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S ... testosterone values used at respective ... Z. Papiæ / EFFECT OF INCREASED

DISCUSSION

Although the present study could not yield a

statistically significant pattern of the parameters

observed because of the relatively small number of

subjects included, we believe it pointed to a

connection between some of the parameters. In the

group with increased serum testosterone, there was a

significantly higher rate of impaired FSH/LH ratio

(Fig. 8), PCOS determined by ultrasound (Fig. 8) and

septate uterus (Figs. 8 and 11). The relation of all

variables in both groups is illustrated in Figure 8,

showing that in group A (subjects with normal serum

testosterone level) the existence of polycystic ovaries

and septate uterus was confirmed in 12% and impaired

FSH/LH ratio in 40% of cases. At the same time, in

group B the existence of polycystic ovaries was

confirmed in 36%, septate uterus in 28% and impaired

FSH/LH ratio in 52% of cases.

The search of MEDLINE index revealed some 230

articles on septate uterus, however, the possible

connection of minor and major uterus abnormalities

with androgenic metabolism has, to date been only

considered by Sorenson in his article published as early

as 1978 (6), yet observing no other correlation.

If we now compare the pregnancy frequencies with

testosterone level (Fig. 9), it is obvious that there were

by far more successful pregnancies in the group with

normal testosterone level, which corresponds to the

results published elsewhere. The subjects with

FSH/LH inversion had the lowest rate of successful

pregnancies, only 15% of cases (Fig. 10), which may be

56

@. Šperanda, Z. Papiæ / EFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S FERTILITY

Figure 9. Rate of pregnancy.

Figure 10. Successful pregnancies: relation of

successful pregnancies and FSH/LH inversion,

increased testosterone and polycystic ovary

syndrome.

Figure 7. Successful pregnancies in group B

according to study parameters (n=25).

Figure 8. Relation of serum testosterone, FSH and LH

with polycystic ovary syndrome and septate uterus

on ultrasound.

Page 5: EFFECT OF INCREASED TESTOSTERONE LEVEL ON · PDF fileEFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S ... testosterone values used at respective ... Z. Papiæ / EFFECT OF INCREASED

57Diabetologia Croatica 33-2, 2004

an important indicator in the treatment of infertility. A

similar rate of successful pregnancies was achieved in

patients with PCO and increased testosterone level,

i.e. about 38%. The results are consistent with

literature data (1,2).

FSH/LH inversion was also found in 70% of the

women with septate uterus (Fig. 11), while the finding

of polycystic ovary was recorded in 60% of the same

subjects.

CONCLUSION

This article shows the results of the analyses

performed in 50 women treated for infertility, divided

into two groups according to serum testosterone level

on the fourth day of their cycles: group A with normal

and group B with elevated serum testosterone. Study

results showed an increased rate of FSH/LH inversion,

PCO syndrome and septate uterus in the group with

elevated testosterone level. It is necessary to conduct a

detailed research on the connection of septate uterus

with the hypothalamus – pituitary gland – ovary axis,

indicated by the results presented. The results of

infertility treatment at smaller clinics like this one are

very successful, along with the fact that such

institutions are very accessible to patients.

We would like to point out that in this way, an

expensive and more complicated in vitro procedure

could be obviated, at least in some patients.

AAcckknnoowwlleeddggmmeenntt.. The authors wish to thank

Academician Zdenko škrabalo for his precious help and

advice on writing the article.

@. Šperanda, Z. Papiæ / EFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S FERTILITY

Figure 11. Women with septate uterus.

REFERENCES

1. Laven JS, Imani B, Eijkemans MJ, Fauser BC. New

approach to polycystic ovary syndrome and other

forms of anovulatory infertility. Obstet Gynecol

Surv 2002;57:755-767.

2. Kousta E, White DM, Cela E, McCarthy MI, Franks

S. The prevalence of polycystic ovaries in women

with infertility. Hum Reprod 1999;14:2720-2723.

3. Katulski K, Bornstein S, Figiel M, Wand D,

Warenik-Szymankiewicz A, Trzeciak WH. Typical

hormonal profiles are accompanied by increased

immunoreactivity of theca folliculi steroid 17 alpha-

hydroxylase P450 in polycystic ovary syndrome. J

Endocrinol Invest 1998;21:304-309.

4. Liddell HS, Sowden K, Farquhar CM. Recurrent

miscarriage: screening for polycystic ovaries and

subsequent pregnancy outcome. Aust N Z J Obstet

Gynaecol 1997;37:402-406.

5. Gilling-Smith C, Story H, Rogers V, Franks S.

Evidence for a primary abnormality of thecal cell

steroidogenesis in the polycystic ovary syndrome.

Clin Endocrinol (Oxf) 1997;47:93-99.

6. Sorensen SS. Hysteroscopic evaluation and

endocrinological aspects of women with mullerian

anomalies and oligomenorrhea. Int J Fertil

1987;32:445-452.

7. Carmina E, Wong L, Chang L, et al. Endocrine

abnormalities in ovulatory women with polycystic

ovaries on ultrasound. Hum Reprod 1997;12:905-

909.

8. Šimuniæ V, et al. Poremeæaji menstruacijskoga

ciklusa (amenoreja, oligomenoreja i kroniène

anovulacije). In: Ginekologija. Zagreb: 2001:205-

215.

Page 6: EFFECT OF INCREASED TESTOSTERONE LEVEL ON · PDF fileEFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S ... testosterone values used at respective ... Z. Papiæ / EFFECT OF INCREASED

9. Šimuniæ V, et al. Poremeæaji menstruacijskoga

ciklusa (amenoreja, oligomenoreja i kroniène

anovulacije). In: Ginekologija. Zagreb: 2001:213.

10. Kupešiæ S. Clinical implications of sonographic

detection of uterine anomalies for reproductive

outcome. Ultrasound Obstet Gynecol 2001;18:387-

400.

58

@. Šperanda, Z. Papiæ / EFFECT OF INCREASED TESTOSTERONE LEVEL ON WOMAN’S FERTILITY