TESTICULAR VOLUME MEASUREMENT: COMPARISON OF PRADER ORCHIDOMETER, ULTRASOUND SCAN AND WATER DISPLACEMENT
A DISSERTATION SUBMITTED
BY
DR MBAERI, TIMOTHY UZOMA MBBS (Port Harcourt) DEPARTMENT OF SURGERY NNAMDI AZIKIWE UNIVERSITY TEACHING HOSPITAL, NNEWI
TO
THE NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PART FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF THE FINAL FELLOWSHIP OF THE MEDICAL COLLEGE IN SURGERY (FMCS)
JUNE 2011
1
DECLARATION I hereby declare that the research project leading to this dissertation was actually carried out by me under the guidance of my supervisors. The work has neither been presented in part nor in full to any other College for a Fellowship; also it has not been submitted elsewhere for publication.
...... DR MBAERI TIMOTHY UZOMA
2
DEDICATION
I DEDICATE THIS WORK TO MY DEAR WIFE AMAKA
WHO BORE THE BURDEN OF MY NEGLECT IN THE COURSE
OF MY PROGRAMME, HER PATIENCE, PRAYERS AND
ENCOURAGEMENT.
TO MY PARENTS MR. AND MRS. REUBEN IBEBUKA
MBAERI WHO INSPITE OF ALL ODDS MADE ME QUALIFY AS A
DOCTOR IN THE FIRST PLACE.
3
CERTIFICATION
This is to certify that I supervised Dr Mbaeri Timothy Uzoma in carrying out the research project leading to this dissertation titled “Testicular volume measurement: Comparison of Prader orchidometer, ultrasound scan and water Displacement”
Signed ...... Prof. Mbonu O.O. MB (Lond), FRCS(Ed), FRCS(C), FWACS, FMCS. Consultant Urologist Department of Surgery Nnamdi Azikiwe University Teaching Hospital Nnewi.
Signed ...... Prof. Orakwe J.C. FMCS, FWACS Consultant Urologist Head Department of Surgery Nnamdi Azikiwe University Teaching Hospital Nnewi.
Signed...... Prof. Nwofor A.M.E. FMCS, FWACS Consultant Urologist Dean Faculty of Medicine Nnamdi Azikiwe University .
Signed ...... Dr .Oranusi C. K. FWACS, FMCS Consultant Urologist Department of Surgery Nnamdi Azikiwe University Teaching Hospital Nnewi.
4
TABLE OF CONTENTS
Content Page
Title Page...... i
Declaration Page...... ii
Dedication Page...... iii
Certification ……………………………………………………………………….iv
Table of Content…………………………………………………………………..v
Abbreviations……………………………………………………………………..vi
Acknowledgement………………………………………………………………..vii
Summary …………………………………………………………………………viii
CHAPTER
1. Introduction……………………………………………………………….1
2. Literature Review……………………………………...... 4
3. Aims and Objectives...... 24
4. Materials and Method……………………………...... 25
5. Results...... 30
6. Discussion…………………………………………...... 41
7. Conclusion and Recommendation…………………………...... 47
References ……………………………………………………………...... 48
Appendix I- Picture of orchidometer
Appendix II- Proforma
Appendix III-Ethical committee approval
5
TABLE OF ABBREVIATIONS
Abbreviation Meaning
L Length
W Width
H Height
Formula 1 Length x Width x Height x 0.52
Formula 2 Length x Width2 x 0.52
Formula 3 Length x Width x Height x 0.71
Sig significance
6
ACKNOWLEDGEMENT
I wish to thank Prof O.O. Mbonu for his fatherly disposition during this work and for the rare honour and opportunity of having him read through my work.
I want to express my profound gratitude to Prof. J.C Orakwe and Prof.
A.M.E. Nwofor my mentors in the strictest sense of the word, who screened my topics, guided me and inspired me all the way from the beginning to the end of this study. They breached protocols; receiving my work on the corridors, offices, in their homes despite their very busy schedule in soft and hard copies for review, constantly urging me on and allaying my fears. The reviews came out as quickly as I made them ready. Prof J.C Orakwe taught me my first orchidectomy, a core component of this study. Prof. Nwofor through his tireless effort got my proposal returned when it was unduly delayed. I shall ever remain grateful to them.
I want to thank specially Dr. C.K Oranusi, through whom my topic finally came with the initial materials to kick start this dissertation, availing me the opportunity to tap from his own experience at no cost.
I thank Dr Akukwe and Abiahu who helped in making sure I got all the samples from my patients for the purpose of this study. Dr Egwuonwu, for his advice and encouragement and my other colleagues who one way or the other, contributed to the success of this study
Finally my gratitude goes to God almighty for giving me the strength and wisdom to make this work a reality.
7
SUMMARY OBJECTIVE: To determine the accuracy of the Prader orchidometer and ultrasound (different methods) for measuring the testicular volume by comparing the resultant measurement with the actual testicular volume in humans.
BACKGROUND: Since seminiferous tubules comprise 80 to 90% of testicular mass, the testicular volume is believed to be an index of spermatogenesis. Therefore accurate testicular volume is one way to assess testicular function.
MATERIALS AND METHODS: The testicular volumes of 121 testes from 62 patients with prostate cancer (mean age 72.74+ 9.38) were measured using the Prader orchidometer and ultrasound before therapeutic bilateral orchidectomy. The ultrasound measurements of testicular volume were calculated using three formulas: length (L) x width (W) x height (H) x 0.52, L X W2 X 0.52, L X W X H X 0.71. The actual testicular volumes were determined by water displacement of the testis.
RESULTS: The mean actual testicular volume of the 121 testes was 10.6+3.5ml. A strong correlation was found between the actual testicular volume and volume calculated by the three ultrasound formulas (r=0.853 to 0.871, p= 0.0001) and Prader orchidometer (r=0.921,p=0.0001). The smallest mean difference from the actual testicular volume was observed with the formula L X W X H X 0.71, which underestimated the actual volume by 0.41ml (3.89%). The measurements using the Prader orchidometer correlated with the testicular volume calculated using the three ultrasound formulas (r=0.848 to 0.854, p= 0.0001). However the orchidometer measurements had a mean difference from the actual testicular volume of 2.66ml (25.14%)
CONCLUSION: The result of this study has shown that measuring the testicular volume by ultrasonography is more accurate than by Prader orchidometer, and the formula L X W X H X 0.71 is the most accurate for calculating the testicular volume.
8
CHAPTER ONE
INTRODUCTION
Testes are the paired oval shaped organs located in the scrotum. They are responsible for the production of spermatozoa and testosterone in man.
The word “testis” is a Latin word enshrined in Roman legal practice as
“testis unus, testis nullus” (one witness equals no witness), meaning that testimony by any one person not corroborated by the testimony of another is to be disregarded. Since two witnesses were needed and they often came in pairs, this was also extended to the testis. Therefore, it is supposed to be a
“Witness” of virility.1
Reliable and accurate determination of testicular volume is of great potential benefit in evaluation of patients with a variety of disorders affecting testicular growth, development and function.
Approximately eighty to ninety percent (80% - 90%) of testicular volume is made up of seminiferous tubules and germ cells.2,3 Thus, a reduction in the number of these cells is manifested by reduction in testicular volume. This was corroborated by Lipshultz et al4 who found that decreased testicular size, whether unilateral or bilateral, correlates with impaired spermatogenesis.
Studies in infertile men have also shown that testicular volume has a direct correlation to seminal fluid and sex hormone assay, just like the simple measurement of testicular length, width and depth.5-8 Total testicular volume
(i.e. summation of right and left) of 30 ml and above is indicative of normal
9
testicular function. 5,6. These findings underscore the great importance of testicular volume measurement in the management of male infertility.
In the management of adolescent varicocele, testicular volume measurement aids in deciding when to operate since getting seminal fluid analysis could be seen to be psychologically and ethically incorrect.9-13.
Other important uses of testicular volume measurement are in the monitoring of patients following varicocele ablation in children and adults, and orchidopexy for undescended testes14,15. It is also a vital tool in staging puberty, as it is the first clinical evidence of puberty16, in making a diagnosis of hypogonadal hypogonadism and Klinefelter’s syndrome. 17-22
Over the years, many instruments have been used in an attempt to accurately, reliably, and conveniently measure the testicular volume in vivo.
These include rulers, tapes, vernier callipers, orchidometry, graphic models and ultrasound scan. Earlier works using these tools have shown conflicting results and the search continues for a more reliable and accurate method of measuring testicular volume. 9-31
While an experienced practitioner can make a good estimate of testicular size, volume measurements are helpful in any multi doctor practice or in the context of multi-centre clinical trials. Furthermore, measurements that are more objective are useful where trainee doctors work alongside experienced practitioners. 30
This study therefore attempts to appraise critically the use of Prader orchidometer and scrotal ultrasound scan as reliable tools for measuring testicular volume while comparing the result with the actual volume obtained by water displacement after orchidectomy in patients with advanced prostate
10
cancer who opt for orchidectomy after counselling in Nnamdi Azikiwe
University Teaching Hospital, Nnewi.
11
CHAPTER TWO
LITERATURE REVIEW
ANATOMY OF THE TESTIS
GROSS ANATOMY:-
The testis is normally located in the scrotum in man. Unlike in man, the testes of whales and elephants are intra abdominal throughout life, while that of rodents and creatures that hibernate, such as hedgehog, moles, and bat, have open inguinal canal allowing for descent of the testes into the scrotum in readiness for the breeding season.32
The average testis in an adult male is an oval organ measuring about 4 x 3 x 2.5 cm. It has a dense fibrous covering called tunica albuginea testis, which invaginates posteriorly into the body of the testis to form mediastinum testis. The fibrous mediastinum sends fibrous septa into the testis, thus separating it into about 250 lobules.33 The epididymis is attached to its postero-lateral surface. Medially there is a distinct groove between them, the sinus epididymis. Both are invaginated into a double serous membrane called tunica vaginalis except the posterior margin of the epididymis, which is free.34The testis and epididymis each bear a tiny appendage, termed the appendix testis and the appendix epididymis respectively.
BLOOD SUPPLY:-
Testicular arteries arise from the aorta just below the renal arteries and course via the spermatic cord to the testes, where they anastomose with the arteries to the vas from the inferior vesical branch of the internal iliac arteries.
12
Blood from the testis returns via the pampiniform plexus of the spermatic cord. The artery and its branches are intimately related to the venous plexus in order to provide a countercurrent heat exchange which helps reduce testicular temperature to 2-4 oC less than rectal temperature.
This temperature is optimal for spermatogenesis.35 The pampiniform plexus of veins becomes a single vessel, the testicular vein, in the region of internal ring. The right drains to the inferior vena cava while the left drains to the left renal vein.
LYMPHATIC DRAINAGE:-
The lymphatic drainage accompanies the venous drainage and thus passes to the para-aortic lymph nodes at the level of the renal vessels.
NERVE SUPPLY:-
The nerve supply is through T10 sympathetic fibres via the renal and aortic plexuses.
HISTOLOGY:-
Each lobule contains 1-4 markedly convoluted seminiferous tubules, each of which measures about 60 cm when teased out. These ducts converge at the mediastinum testis where they connect with the efferent ductules that drain into the epididymis. The seminiferous tubule has a basement membrane containing connective and elastic tissue.33 This supports the seminiferous cells namely the sertoli cells and the spermatogenic cells. Sertoli cells serve as “nurse” cells for spermatogenesis, nourishing germ cells as they develop 2 .
13
They secrete androgen binding globulin which by binding testosterone ensures that high levels of androgen (20-30 times that of serum) exist within the seminiferous tubules.2 It also secretes inhibin which regulates the secretion of follicle stimulating hormone by feedback mechanism.2 The stroma between the seminiferous tubules contains connective tissue in which the interstitial cells of Leydig are located.33 The Leydig cells constitute the endocrine portion of the testes, secreting testosterone.35
14
FACTORS AFFECTING TESTICULAR VOLUME
The average adult testicle size measures 4 x 3 x 2.5cm.2 Bilateral atrophy may occur in a variety of conditions including chronic alcoholism, hypopituitarism, chemotherapy, irradiation, post pubertal mumps, liver cirrhosis, and exposure to insecticide (dibromochloropropane).2
Other causes include
AGE:-
From birth to puberty (13-14 years), there is very little increase in testicular size and a size of 5 ml or less may be considered juvenile. After 13-
14 years however, there is a rapid increase in testicular size; at 17 or 18 years, the adult size is reached. It remains relatively constant afterwards. 26,36
Kuijper et al37 using ultrasound noticed finer changes in testicular volume which would not have been noticed by the orchidometer and calliper used by Takihara et al26 and Rundle et al36 respectively. In their study of children aged 0 to 6 years, they noted that mean testicular volume increased from 0.27 ml at birth to 0.44 ml at about 3 to 5 months. It then declined afterwards to 0.31 ml at 9 months and remained so until 6 years.37
This transient increase noted by Kuijper et al37 during infancy coincides with the ‘mini puberty’ described by Anderson et al38 who found a transient rise in gonadotropin-releasing hormone between 3 – 5 months of age. The biological reason for this is not clearly understood, but it has recently been suggested that it aids the normal development of the external genitalia
(scrotum and penis)39,40.
Before puberty the seminiferous tubule is non-luminal and the increase in testicular volume is minimal and mainly due to increase in seminiferous 15
tubule length41. From the beginning of puberty however, the seminiferous tubule becomes luminal and increases rapidly in diameter mainly due to a dramatic increase in germ cell number, cytoplasmic development of sertoli cells, and an increase in androgen binding protein. This is the main cause of pubertal increase in testicular volume41.
The other period of life, which affects testicular volume, is aging42,43.
After exclusion of men with diseases known to be associated with reduced testicular size, the specific effect of age demonstrates a reduction in testicular volume only after the eight (8th) decade42. The mean testicular volume in men over 75 years is 31% smaller than their 18 to 45 year old counterparts43. The aging related reduction in testicular volume may be explained by the reduction of seminiferous tubule length and corresponding reduction in sertoli cells and germ cells at this period44.
BODY SIZE:-
Raji et al45 studying two goat species in the northern part of Nigeria noted a strong correlation between testicular length and circumference as measured by vernier callipers and cloth tape respectively and body weight. In their study however, the testicular length for convenience was estimated to be equal to scrotal length which of course is an over estimation. More so, they studied goats, which may not be a good analogy for man. Ku et al46 in their study of 1792 men, undergoing medical check up for conscription into the military in South Korea, demonstrated a correlation, though weak, of testicular volume with height, body weight and body mass index.
16
Another study in Ilorin, Nigeria of 20 fertile men and 48 infertile men showed a correlation between testicular volume and height but not with weight and ponderal index.47 The variation between these two studies may have arisen from the huge difference in their sample size i.e. 1792 and 68 respectively. In addition, though the fertility status of those studied by Ku et al46 was not checked, approximately 70.5% of those studied by Sobowale et al47 were infertile which is rather on the high side. This may be a confounding factor.
ETHNICITY AND RACE:-
The normal adult testicular size amongst Japanese in Yamaguchi medical school was found to be 17.59+/- 1.91 ml while the normal adult testicular size amongst Americans in University of Rochester New York was
24.8+/- 3.5727. Main et al48 in their study of 633 Danish and 1044 Finnish boys, showed the testicular size of Finnish boys to be significantly larger than that of the Danish boys at birth, 3 month and 18 months. This may point to genetic differences in testicular size.
However a study by Kuijper et al37 in children of different races
(Caucasian, Mediterranean, African and Asian) residing in Amsterdam
Netherlands showed no difference in testicular volume. Thus, the apparent difference in testicular volume in people of different ethnic/ racial groups is probably from environmental influence.37 Ku et al46 demonstrated the influence of environment in their study. They found that the likelihood of a low total testicular volume varied with area of residence, with a 1.6 fold greater risk in men in large rural areas than in those in major towns. They also found
17
the likelihood of having a smaller testicular size to be inversely related to environmental temperature. So demographic and environmental factors affect testicular size46.
IN-UTERO EXPOSURE TO CIGARETTE SMOKING
There is reduced semen quality and smaller testicular sizes in young men exposed to smoking in-utero compared with men without exposure49 This study was however, a questionnaire-based study that needed the input of the mothers (who may feign selective amnesia) on whether they smoked prenatally or not. In addition, other confounding factors like prenatal alcohol intake, diet, and other drug use were not considered. Thus, taking all of these into consideration, more work needs to be done to confirm this claim.
VARICOCELE:-
This is dilatation, elongation and tortuosity of the pampiniform plexus of veins. Studies have reported an association between clinical varicocele and ipsilateral testicular growth retardation10-12,50,51. There is also a demonstrable catch up growth following varicocele ablation 11,15,51,53.
The mechanism by which varicocele causes these is not well known.
However postulations are that; (i) varicocele results in an increase in testicular temperature that suppresses spermatogenesis, (ii) reflux of adrenal and renal metabolites (iii) decreased blood flow with stasis54 . The recent interest in molecular biology has pointed to high oxidative stress with a consequent rise in reactive oxygen specie (super oxide anion, hydroxyl radical and hypochloride radical). These cause damage to cell membrane by peroxidation
18
of the lipid content. The spermatozoa are particularly susceptible as they have a large polyunsaturated fat content in their membranes. The reactive oxygen specie also causes direct DNA damage and apoptosis54
UNDESCENDED TESTIS:-
An undescended testis develops poorly even after orchidopexy compared to the descended contralateral testis 14,55-57. Osifo et al14 in Benin noted that orchidopexy in prepubertal & pubertal period gave better result compared to post pubertal period.
KLINEFELTER’S SYNDROME:-
With an incidence of 1 in 500 new births, it is a common chromosomal anomaly characterised by the presence of at least two (2) or more X- chromosome and one (1) or more Y-chromosomes2,17.
Clinically they present with reduced testicular volume, azoospermia, gynaecomastia and elevated gonadotropin levels17,18. There is variation in the frequency of each component of these clinical features. The most common ones are reduced testicular volume and azoospermia which is present in 99-
100% of patients17. Kamuschke et al18 found a mean bitesticular volume of
4.7+0.3. Using callipers the bitesticular volume is 5.03 ml (right=3.33, left=1.7)19. The testes are usually less than 2 cm in length and always less than 3.5 cm.2 The range is 0.9 cm – 3 cm (right) and 1.2-2.4 cm (left).In addition, the testicles are usually firmer than normal due to fibrosis of the seminiferous tubules.17
19
CLINICAL USES OF TESTICULAR VOLUME MEASUREMENT
Normal male virility and fertility require the collaboration of the exocrine and endocrine testicular functions i.e. production of spermatozoa and testosterone respectively2. Reliable and accurate determination of testicular volume is of great benefit in evaluation of patients with a variety of disorders affecting testicular growth, development and function.
FERTILITY ASSESSMENT:-
Since seminiferous tubule comprise 80-90% of testicular mass, testicular volume reflects spermatogenesis2,3 . In line with this, one of the components of a minimum full evaluation for male infertility is palpation of the testes and measurement of their sizes58.
Testicular volume correlates with semen profile and has been useful in estimating spermatogesis5-7,11,15,53,59. Aria et al6, in their study of correlation between testicular volume (using punched out orchidometer) and semen profile in 486 infertile Japanese men, found that testicular volume had the strongest positive correlation with sperm density, followed in decreasing order by total sperm count per ejaculate, total motile sperm count per ejaculate and percentage of motile sperm count. The critical bitesticular volume indicating normal testicular function was 30 ml6. In contrast, they found no significant correlation between testicular volume and semen volume. Patients with total testicular volume of less than 10 ml were azoospermic, while volumes of less than 20 ml were associated with severe oligospermia6. Their findings were corroborated by Sakamoto et al5 in their study of 389 infertile Japanese men using Prader orchidometer and ultrasound, but in addition noted that the 20
critical total testicular volume for normal testicular function is 20 ml using ultrasound scan. It is worthy to note that this relationship is influenced in patients with varicocele59. This supports the belief that measurement of testicular volume could be helpful in rapidly assessing fertility at the initial physical examination.
Sobowale et al47 in Ilorin Nigeria, in their study of 20 fertile and 48 infertile men did not agree with this. They found no correlation between testicular volume measured by callipers and sperm density and total sperm count per ejaculate. The sample size in their study however was very small compared to sample size used by Arai et al6 and Sakomoto et al5. More so, the sample population were different in characteristics. 29.4% of the sample size by Sobowale el al47 were fertile while the other two group had no (0%) fertile population in their study.
VARICOCELE MANAGEMENT:-
Varicocele is the commonest surgically correctable cause of infertility though the argument still rages2,3,54. Many workers have attempted to correlate varicocele and infertility 10,13,15,54. In adolescent varicocele, fertility is undefined and thus is not an issue29. Testicular damage at this age is best reflected by loss of volume and consistency of the involved testis relative to the uninvolved testis10-12,50,53,54. Some researchers suggested that a volume differential of 20% to 25% is clinically significant 9,10,13.
Diamond et al29 in their study of 65 boys aged 7 to 24 years sought to check the sensitivity of orchidometer to detect volume differentials of 10%,
15%, 20% and 25% between both testes compared to ultrasound scan. They
21
found that orchidometer sensitivity was 50% (weak).This is not unexpected as they used the formula L x W2 x 0.52 which has been shown to reduce markedly the actual testicular volume 27,28. Although the orchidometer remains valuable in serially following the size of individual testis, it is too insensitive for volume differentials to be used routinely to determine growth impairment secondary to varicocele9,25,29. Thus, observation for an adolescent with varicocele should include annual ultrasound measurement of testicular volume29.
Volume measurement can also be used for assessment of testicular growth or atrophy postoperatively 9.
OTHER USES:-
Testicular volume enlargement of 4 ml or greater is used as a clinical landmark for the onset of puberty16. In boys, delayed sexual development is defined as no testicular enlargement by 14 years of age, or the passage of five years between the initial and complete development of the genitalia60.
Pubertal staging allows doctors to assess the maturation of adolescent patients; to correlate several pubertal phenomena, growth spurt, and final height; to offer early orientation to youngsters in relation to upcoming pubertal events; to offer advice on choice of proper sports modalities; and to treat pathologies associated with puberty61.
Staging of sexual maturation is carried out with genital and pubic hair growth for boys. In this sense, pubertal staging is an important measure for characterizing the maturation of adolescents and for easier understanding and handling of the most common clinical problems for this age group40,61.
22
Measuring testicular volume is also important for the assessment and diagnosis of certain pathologies, namely: cases of Klinefelter’s syndrome
(small testes) or of Fragile-X syndrome (possible macro-orchidism) and idiopathic hypogonadism 17,19-21,40.
The follow-up measurement of testicular volume is important in post- surgical follow-up of orchidopexy (to check whether ectopy, twisting and/or surgical handling has affected testicular development), record growth following hormonal therapy, and finally pre-surgery to match more closely testicle with a prosthetic one. 61
23
CLINICAL METHODS OF MEASURING TESTICULAR VOLUME
Various attempts have been made in an attempt to reliably, and accurately measure testicular volume in man. The methods in use include the ruler, graphic model, callipers, orchidometer and most recently ultrasound scan.
RULER:-
Comparing three commonly used methods of testicular volume measurement, ruler, orchidometer and ultrasound, Taskinin et al62 found a significant correlation among the three methods. They recommended the use of ruler because of its simplicity, availability and low cost. When using the ruler the longitudinal and transverse axis are measured. The volume is calculated as k x longitudinal axis x (transverse axis2). The k constant is
0.7162 or 0.52361.
GRAPHIC MODEL:
This was introduced by Chipkevitch et al in 199623. They compared the reliability of 5 methods of testicular volume measurement namely dimensional measurement using ruler or callipers, Prader orchidometer, ring orchidometer, ultrasound scan and a new modality introduced by them ”Graphic model”23.
Here the testis is palpated and visually compared with graphic models. Testis volume is determined according to one of the six volumes or the intermediate volume between two consecutive volumes depicted. The entire measurement scale includes 13 volumes <2 ml, 2 ml, 3.5 ml , 5 ml, 7.5 ml , 10 ml. , 12.5 ml ,
15 ml , 17.5 ml, 20 ml., 22.5 ml, 25 ml and >25 ml. They concluded that the 24
graphic model is simple and its reliability is comparable to that of orchidometer and ultrasound scan23
CALLIPERS:-
Several workers have used callipers in measuring testicular volume
26,40,47,55,57. With callipers the length and width of each testis is measured and the volume is determined on the assumption that the testis was the shape of an ellipsoid of revolution, i.e.
TV=0.52 x L x B2
Lambert in 1951 compared the size of the normal adult testis with subjects who had mumps orchitis. He showed that the formula for rotation of an ellipsoid gave results that were inaccurate, and devised an empirical formula as follows.
TV=0.71 x L x B x Depth.
But Rundle et al36 in their work on assessment of maturation noted that the manipulation to exclude the epididymis to get the depth introduced greater error than the assumption that the breadth and thickness were same and for that reason only the length and breadth were measured in their work. Thus the modified Lambert formula
TV=0.71 x L x B2.
The determination of different diameter in an oval structure is a time- consuming procedure that may be uncomfortable for the patient especially in the case of children and adolescent since it involves the considerable manipulation of the genitalia26 . In the case of small testes, the thickness of the skin and subcutaneous tissue may strongly influence the result 62. During
25
measurement, the testis easily becomes compressed, resulting in distortion of shape and dimensions, which affects the volume62.
ORCHIDOMETER:-
There are three different types of orchidometer namely; Prader orchidometer, Punched out orchidometer, Seager orchidometer (Orchometer).
a) Prader Orchidometer: - Prader first described this in 1966. Prader
designed models having the exact form of ellipsoids, comprising 12
models graded from 1 to 25 ( 1,2,3,4,5,6,8,10,12,15,20 and 25 ml)
attached to a string. To assess testicular volume, the examiner palpates
the testis with one hand while holding the orchidometer in the other,
examining the patient for the model that is closest in size to the testis.
Although many workers have used Prader orchidometer5,9,14,16,23-25,27-
30,37,63-65, there is still no consensus on its accuracy and reliability.
While some think it is neither accurate nor reliable9,25 , Schiff et al24 reported that orchidometer measurement correlated closely and significantly with ultrasound measurement (formula L x W x H x 0.71). In their study the mean Orchidometer testicular volume (18.3 ml on the right and 16.9 ml on the left), did not differ significantly from the mean Ultrasound volume (18.4 ml on the right and 17.1 ml on the left)24. Other studies showed a strong linear relationship between orchidometer measurement and ultrasound, although orchidometer often overestimated the testicular volume relative to ultrasound27-31,62,63.
26
The degree of overestimation depends on the experience of the examiner in the use of the Prader orchidometer24,29. Diamond et al29 studied
65 males in Boston Massachusset and found a consistent overestimation of about 2 ml by a less experienced examiner (Nurse) compared to a more experienced examiner (board certified urologist). This finding was corroborated by Schiff et al24 who in their work on 159 men and 314 testes by an examiner who is familiar with, and experienced in the use of the Prader orchidometer found that it is a very accurate method of assessing testicular volume provided the scrotum is warm and the dartos muscle relaxed.
Tatsunami et al64 did not agree with this view. In their quality control study of intra-observer and inter-observer reliability of 10 andrologist with a mean experience of 11 years (4 to 21 years), they found no correlation between accuracy of orchidometer measurement and experience. However their study sample comprised only 12 volunteers. Moreover, andrologic experience is not synonymous with experience in use of Prader orchidometer.
Karaman et al65 in their study of 100 testes by three observers found a strong correlation between the three examiners, though they also did not state their experience in the use of Prader orchidometer. The inter-observer variability in my opinion should be looked at critically from the point of view of Prader orchidometer user experience.
Another factor, which affects the accuracy, is the size of the testis. The smaller the testis, the more the percentage overestimation relative to the actual volume5,25,26,31,63. Since in using Orchidometer the skin and subcutaneous tissue are measured as well, the percentage thickness of skin and subcutaneous tissue is relatively high 5,25,26,31,63. The higher the volume,
27
the less the percentage overestimation. However, for volumes greater than 25 ml the orchidometer rather underestimates the volume. This is because the highest model is 25 ml 28,63.
When measuring testis size by the orchidometer, we must be aware that the skin and subcutaneous tissue are measured as well31. This also contributes to the over estimation. Scrotal skin thickness is constant for the majority of people, the range being 2 to 3 mm; but higher in people with
Klinefelter and testicular torsion31. An attempt to reduce this added volume led to the advice that the measurement be done in a warm room or after application of warm pad for about 5 min before measurement to encourage relaxation of dartos muscle24,26,28,31. Other factors, which may affect overestimation, are visual comparison error and size of epididymis9,31,36.
It is suggested that proper standardization of the Prader orchidometer measurement technique such as periodic comparison with ultrasonography result will be necessary to improve accuracy64
Finally, in the hands of an experienced examiner the orchidometer is an accurate method of assessment of testicular volume when the scrotum is warm and the dartos muscle is relaxed24
b) Punched-out Orchidometer: - This is also known as Rochester University,
Yamaguchi University or Takihara orchidometer32. It was introduced in
1983 by Takihara et al26 and has also been used by many workers
6,27,29,30,31,63. It consists of graded series of punched out elliptical rings with
the number on each indicating the volume of the ellipsoid ranging from 1 to
35 ml( 1-6, 8, 10, 12, 14, 16, 20, 22, 26, 30). The proper ring is placed
28
over the stretched scrotal skin away from the epididymis up to the
midportion of the testis, and the volume is read from the oval ring with the
best fit26. The accuracy and reliability are akin to what is obtainable with
Prader orchidometer23,29,30.
. c) Seager Orchidometer (Orchometer):- The Seager Orchidometer (SO) is an
ideal measuring device for obtaining, in a clinical situation, testicular size
and volume in both adult and paediatric urology and andrology. A unique
testicular volume chart in cubic centimetres is imprinted on the back of
each orchidometer. Once the testicular length and width have been
obtained, the volume can be read from this table. An added advantage of
the Orchidometer is its use also for measurement of penile size and
volume62. The Seager orchidometer is slightly more difficult to use than
the others: two measurements must be made and the measurement of
testicular length can be particularly difficult to make when the scrotal skin
is stretched30.
ULTRASOUND SCAN:-
Ultrasound scans are generally recognized as the most accurate volume measurement method, but in the absence of standardization previous ultrasound studies have varied considerably regarding the formulas used to calculate testicular volume 5-7,25,27,28,30,32,62,63. Two recent studies show testicular volume calculated using the ultrasonographic formula L × W × H ×
0.71 to be the closest to actual testicular volumes27,28. Paltiel et al27 working on 18 canine testes, compared the volumes measured by Prader
29
orchidometer, punched out orchidometer, and ultrasound scans with actual volume.
For the ultrasound they used the formulae;(a) the formula for an ellipsoid: length (L) x width (W) x height (H) x 0.52 7,9,15,39, (b) the formula for a prolate spheroid: L x W2 x 0.52 25,29,30, and (c) the empiric formula of Lambert:
L x W x H x 0.71 5,12,24,31,53,59,62,63 , which have been in use by various workers.
They concluded that ultrasound methods of testicular volume measurement are more precise and accurate than orchidometry and that the formula L x W x
H x 0.71 provides a superior estimate of testicular volume and should be used in clinical practice.
Their use of canine testis and only 18 testes may be adjudged inappropriate to make a conclusion. However, a more recent (2007) similar study in man by Sakamoto et al28 using 40 testes came to the same conclusion.
Scrotal ultrasound is relatively expensive for routine use in andrology clinics. During ultrasound measurement, the testis easily becomes compressed, resulting in distortion of shape and dimensions31. In addition, if the axis of the testis is not perpendicular when using ultrasound, the formula is not accurate27,31,62.
For volume differentials as is necessary in determining growth impairment secondary to varicocele in adolescent and other testicular pathology, the patient will benefit from ultrasound 9,25,29.
Ultrasound testicular volume measurement like any other ultrasound procedure is operator dependent. In most of these studies, the researchers went for the “best”, that is the most senior among the radiologist. The question
30
is, will they always be there in routine practice? All these should be taken into consideration in advocating solely for ultrasound.
WATER DISPLACEMENT;
This is the most accurate method of determining testicular volume but cannot be used in vivo as the testis would have to be removed first.25,28,66
Here water is put into a measuring cylinder and the water level is recorded.
After the epididymis is removed by sharp dissection, the testis is dropped into the water and the new water level following immersion of the testis is recorded. The volume of the testis is equal to the volume of water displaced.66
31
CHAPTER THREE
AIMS AND OBJECTIVE
GENERAL
1. To critically appraise the use of Prader Orchidometer and Ultrasound
scans in measuring testicular volume
2. Correlate testicular volume using Prader orchidometer and ultrasound
scans with testicular volume obtained by water displacement.
SPECIFIC
1. To determine the accuracy of Prader orchidometer in measuring
testicular volume.
2. To determine the accuracy of ultrasound, in measuring testicular
volume.
3. To verify the best formula for calculating ultrasound determined
volume.
4. To determine the relationship between measurement of testicular
volume by Prader orchidometer and ultrasound.
32
CHAPTER FOUR
MATERIALS AND METHOD
This was a 19 month (from June 2009 to December 2010) hospital based cross-sectional prospective study of the testicular volume of patients with advanced prostate cancer who were offered bilateral orchidectomy as a form of hormone ablation therapy in Nnamdi Azikiwe University Teaching
Hospital(NAUTH) Nnewi.
STUDY AREA
The study centre is Nnamdi Azikiwe University Teaching Hospital, located in Nnewi, Anambra state. It draws patients from Anambra state mainly but also from the neighboring states of Imo, Abia, and Delta. With three urology teams headed by five consultant urologists. It is a referral centre for urological patients.
ETHICAL CONSIDERATION
The Research and ethical committee of Nnamdi Azikiwe University
Teaching Hospital gave approval for the study. Furthermore, patients who had advanced carcinoma of the prostate confirmed by histological examination were duly counseled for hormone ablation therapy and the options available.
Only those who accepted bilateral orchidectomy, met the inclusion criteria and gave consent for the study were enlisted. The patient’s privacy was protected throughout the study. All the information obtained from the patients was handled in strict confidence.
33
STUDY POPULATION
Patients with prostate cancer who presented to the Nnamdi Azikiwe
University Teaching Hospital Nnewi.
SAMPLE SIZE
Using the formula for a population less than 10,000.67
nf= n 1+ (n) (N)
Where nf= the desired sample size (when population is less than 10,000)
n= sample size for population greater than 10,000 = z2 pq d2 N= estimate of population size= number of patients with prostate cancer seen in Nnamdi Azikiwe University Teaching Hospital yearly = 110
z=the standard normal deviate, set at 1.96, which corresponds to the
95 % confidence level.
p= proportion of prostate cancer in Nigeria (target population). Here
10% is used as this is the prevalence for men 40 years and above with prostate specific antigen >/= 4ng/ml reported by Ukoli et al.68 Since some other prostatic disease can also raise the PSA, this value may be on the high side but is however the available prevalence. = 0.1
q= 1-p (1-0.1) = 0.9
d= degree of accuracy desired, 0.05
Thus n= (1.96)2(0.1) (0.9)
(0.05)2
= 138.30
34
since nf= n 1+ n N
nf= 138.30 1+ 138.30 110
= 61.19
= 62
INCLUSION CRITERIA
Men with histologically confirmed advanced prostate cancer who consented to bilateral orchidectomy and the study
EXCLUSION CRITERIA
All patients who had hydrocele, painful testis and oedematous scrotum were excluded. Also excluded were those who had been placed on any other form of hormonal, radiation or surgical treatment before presentation and those who did not give consent for the study.
METHODS
Permission was obtained from all the unit consultants in urology unit in
Nnamdi Azikiwe University Teaching Hospital. The study protocol included a detailed history, physical examination and ancillary investigations as is in the study proforma (appendix II). The patients scrotum and contents were examined and the testicular volumes measured with a Prader orchidometer.
The examinations were done in a warm room after application of a heating
35
pad to the scrotum for about 5 minutes. The testes were then gently isolated and distinguished from the epididymis; and the scrotal skin stretched without compressing the testis. Using the orchidometer, a manual side-by-side comparison between the testis and the beads were made to Identify the bead most similar in size to the testes; this indicated the testicular volumes.
Scrotal ultrasound scans were also done for the patients with a 7.5
MHz probe by a consultant radiologist checking for any scrotal pathology and measuring the length, breadth (transverse diameter) and depth (anterior posterior diameter) of the testes. The volume was calculated using the formula for an ellipsoid: length (L) x width (W) x height (H) x 0.52; (b) the formula for a prolate spheroid: L x W2 x 0.52; and (c) the empiric formula of
Lambert: L x W x H x 0.71 .
Orchidectomies were then performed for the patients, tagging the right testis for identification and removing the epididymis by sharp dissection. The actual testicular volumes were measured by water displacement method using a measuring cylinder. All the results were recorded in the study proforma.
Data Analysis: Statistical analysis was done using Statistical Package for
Social Sciences (SPSS) version 17.0. Simple frequencies were determined for age and descriptive statistics for the testicular volume measurements. Test of significance for testicular volumes was done using paired sample T-test and correlation was done using Pearson correlation coefficient.
36
LIMITATION OF STUDY
1. The ultrasound results depended on the single radiologist selected for the
study to reduce inter-observer error. Who was not always present.
2. The same ultrasound machine serving the whole hospital community was
used and solely depended on.
3. The study had a preponderance of elderly people whose testes may be
small, a factor known to affect the accuracy of orchidometer.
37
CHAPTER FIVE
RESULTS
This study was carried out over a period of 19month, from 1st June 2009 to
31st December 2010. A total of 62 patients were studied. Fifty-nine patients
had bilateral testes, two had only the right testis and one had only the left
testis. So only 121 testes were used in this study.
The age ranged from 55 years to 92 years with a mean age of 72.74+
9.38 years. The peak age group was in the age range 71 to 75 years, which
had 18 patients (29%) (figure 1).
Age Range and Frequency 20 18 16 14 12
10 8 6 4
FREQUENCY 2 0 51-55 56-60 61-65 66-70 71-75 76-80 81-85 86-90 91>
AGE AgeRANGE Range IN in YEARS Years
Figure 1 Distribution of patients by age
38
All the patients were married and of the Igbo ethnic group
The mean testicular volume measured by Prader orchidometer was
13.26+5.21ml (range 6 to 25). The mean volume by ultrasound formula 1 was
7.62+3.37ml (range 2.85 to 16.10). The mean volume by ultrasound formula 2 was 6.51+3.00ml (range 2.21 to 14.80). The mean volume for ultrasound formula 3 was 10.18+4.41ml (range 3.87 to 21.18). The mean actual testicular volume as measured by water displacement was 10.60+3.50ml (range 4.40 to
20.00). (Table I)
Table I
Testicular volume measurement Descriptive Statistics
Instrument N Minimum Maximum Mean Std. Deviation Orchidometer 121 6.00 25.00 13.2562 5.20821 Ultrasound formula 1 121 2.85 16.10 7.6228 3.36671
Ultrasound formula 2 121 2.21 14.80 6.5107 2.99507
Ultrasound formula 3 121 3.87 21.18 10.1816 4.41072
Water Displacement 121 4.40 20.00 10.5934 3.50178
Valid N (listwise) 121
39
Neither the Prader orchidometer nor the ultrasound measurements provided testicular volumes which corresponded with the actual testicular volume. The ultrasound using all the formulas, underestimated the testicular volume while the Prader orchidometer overestimated the testicular volume.
The Prader orchidometer overestimated the testicular volume by
2.66+2.41ml, the ultrasound formula 1 underestimated by 2.97+1.87ml, the ultrasound formula 2 underestimated by 4.08+1.80ml while ultrasound formula
3 underestimated by 0.41+2.19ml. Ultrasound formula 3 was the most accurate as it underestimated the actual volume by only 3.89% compared to underestimations by ultrasound formula 1 of 28.04%, formula 2 of 38.54% and overestimation by Prader orchidometer of 25,14% ( Table II).
The mean difference between the actual testicular volume and ultrasound formula 1, ultrasound formula 2 and ultrasound formula 3 were found to be statistically significant (p<0.0001, p<0.0001, p<0.05 respectively).
(Table II)
40
Paired Samples Test Between Water Displacement And Others
Paired Differences 95% Confidence Interval of the Difference Percent (%) Std. Error Sig. (2- Mean Mean Std. Dev. Mean Lower Upper T df tailed) Pair 1 Orchidometer – Water 2.66281 25.14 2.40857 .21896 2.22928 3.09634 12.161 120 .000 Displacement Pair 2 Ultrasound formula 1 – -2.97058 -28.04 1.86854 .16987 -3.30690 -2.63425 -17.488 120 .000 Water Displacement Pair 3 Ultrasound formula 2 – -4.08273 -38.54 1.79755 .16341 -4.40627 -3.75918 -24.984 120 .000 Water Displacement Pair 4 Ultrasound formula 3 – -.41182 -3.89 2.19305 .19937 -.80655 -.01708 -2.066 120 .041 Water Displacement
41
Table III shows the correlation between measuring instruments.
Though the mean difference between the actual testicular volume and the ultrasound formulas were statistically significant, all three ultrasound volumes correlated strongly with the actual testicular volume with Pearson correlation coefficient r =0.853, p<0.0001; r = 0.858, p< 0.0001 and r = 0.871, p< 0.0001 for ultrasound formulas 1,2 and 3 respectively ( Table III and Figures 2, 3 and
4).
42
Table III
Correlation Between Measuring instruments
Water Orchidomet Ultrasound Ultrasound Ultrasound Displaceme er formula 1 formula 2 formula 3 nt Orchidometer Pearson 1 .854** .861** .848** .921** Correlation Sig. (2-tailed) 0.0001 0.0001 0.0001 0.0001 N 121 121 121 121 121 Ultrasound Pearson 0.854** 1 0.960** 0.984** 0.853** formula 1 Correlation Sig. (2-tailed) 0.0001 0.0001 0.0001 0.0001 N 121 121 121 121 121 Ultrasound Pearson 0.861** 0.960** 1 0.972** 0.858** formula 2 Correlation Sig. (2-tailed) 0.0001 0.0001 0.0001 0.0001 N 121 121 121 121 121 Ultrasound Pearson 0.848** 0.984** 0.972** 1 0.871** formula 3 Correlation Sig. (2-tailed) 0.0001 0.0001 0.0001 0.0001 N 121 121 121 121 121 Water Pearson 0.921** 0.853** 0.858** 0.871** 1 Displacement Correlation Sig. (2-tailed) 0.0001 0.0001 0.0001 0.0001 N 121 121 121 121 121 **. Correlation is significant at the 0.01 level (2-tailed).
43
Figure 2
In figures 2, 3 and 4 the central black lines represent the regression line with their r2 value while the blue lines are their 95% confidence interval around their mean.
44
Figure 3
45
Figure 4
The mean difference in testicular volume between Prader orchidometer and the actual testicular volume measured by water displacement was also statistically significant by the paired t test (p<0.0001). It however also correlated strongly with the actual testicular volume with correlation coefficient of r=0.921 and p<0.0001(Table III and Figure 5)
46
Figure 5
Comparing the mean volume of Prader orchidometer and that of all the three ultrasound formulas showed that ultrasound had a lower mean testicular volume. The ultrasound formula with the least mean testicular volume difference is however that of ultrasound formula 3 which is -3.07+2.76.
The mean volume difference between all the ultrasound formulas and
Prader orchidometer was statistically significant (p<0.0001, p<0.0001, 0.0001)
(Table IV). All three ultrasound formulas however correlated strongly with the
47
Prader orchidometer volume. The Pearson correlation coefficient r was 0.854,
0.861 and 0.848 for formulas 1, 2 and 3 respectively see (Table III)
Table IV
Paired Samples Test Between Orchidometer and Ultrasound formulas
Paired Differences 95% Confidence Interval of the Difference Perce Std. Std. Sig. nt (%) Deviatio Error (2- Mean Mean n Mean Lower Upper T df tailed) Pair Ultrasound -5.63339 -42.50 2.91796 .26527 -6.15860 -5.10817 -21.237 120 0.000 1 formula 1 – Orchidometer Pair Ultrasound -6.74554 -50.89 3.04069 .27643 -7.29284 -6.19823 -24.403 120 0.000 2 formula 2 – Orchidometer Pair Ultrasound -3.07463 -23.19 2.76386 .25126 -3.57211 -2.57715 -12.237 120 0.000 3 formula 3 – Orchidometer
48
CHAPTER SIX
DISCUSSION
DEMOGRAPHY
The mean age of patients in this study was 72.74+ 9.38 years. This is similar to the mean age of 74.5+7.5 years reported by Sakamoto et al28 who studied testicular volumes of 40 testes in 20 patients. A study by Ogunbiyi et al69 in Ibadan Nigeria on the incidence of prostate cancer in Nigeria gave the mean age of 71.4 years (variance 14.3). Thus considering that this study was done in patients with prostate cancer as our study population this age range of 72.74+9.38 years is not unexpected.
TESTICULAR VOLUME MEASUREMENT BY WATER DISPLACEMENT
The mean actual testicular volume measured by water displacement was 10.6+3.5ml (4.4 to 20.0) in this study. This mean actual testicular volume is the same as what Hsieh et al66 got in a similar work in China. He got a volume of 10.6ml. It is however different from what Sakamoto et al28 got. They got a mean actual testicular volume of 9.3+ 4.5ml. This difference may be said to have arisen from his study of a smaller number of testes (40) compared to the 121 testes we studied. But Hsieh et al66 who got a similar mean volume studied only 30 testes, which is even smaller than what Sakamoto et al studied. Therefore, the sample size alone cannot explain the difference.
In the study by Sakamoto et al, the mean age of his patients was
74.5+7.5 years and no range was given. Since his study population was small, it meant that the presence of a few extremely low age groups could bring down the mean age of his perhaps older patient population. If this is 49
true, it could explain why his mean actual testicular volume is lower since testicular volume (though relatively constant after puberty) has been found to start decreasing from the eight decade of life.42,43 However in this study, there was no clear relationship between testicular volume and advancing age unlike the study by Handelsman et al42 . Also the fact that we studied different population group; they studied people in Tokyo Japan and I studied the population in Nnewi Nigeria could account for the difference. Since environment and race have also been found to influence testis volume.27,46,48
ACCURACY OF PRADER ORCHIDOMETER
The Prader orchidometer overestimated testicular volume by 25.14%
(2.66mls) in this study. It has been shown to overestimate the actual testicular volume by a lot of other studies to varying degrees.25,28,66 Paltiel et al27 in their study of 18 canine testes showed the orchidometer overestimated testicular volume by only 12%(1.6ml). The actual cause of this difference is not certain but it should be noted that he used dog testes and not human testes. Secondly, he did not measure the actual size of testes by water displacement like was done in this study. He got the testicular volume by weighing the testis and converting with the formula volume= weight/density while assuming that the density of dog testis is the same for human testis.
Though the density of human testis has been found to be constant at 1.038 by
Handerlsman et al42 the assumption by Paltiel et al27 that the density of dog testes should be the same as that of humans is not entirely correct. In addition, the skin of dog scrotum may also have a different texture compared to that of human scrotum.
50
On the other hand, Sakamoto et al28 found that Prader orchidometer overestimated the mean testicular volume by 81.7% (6.68ml). In his methodology, though they said the Prader orchidometer measurement was done by one experienced urologist, no mention was made of whether he attempted to exclude the epididymis which is one of the things that have been found to reduce the accuracy of Prader orchidometer.9,31,36 Also it was not mentioned if the water displacement was done by the same urologist or if he was aware of the ultrasound results. These factors have been suggested as likely to improve the accuracy of the orchidometer measurement.64
Rivkees et al25 showed that Prader orchidometer only over estimated by 30%. In his study however, he used animal models. They used the testes of 10 calves and 9 dogs and an artificial scrotum to simulate human scrotum.
They also found that Prader orchidometer overestimates testicular volume to varying degrees depending on the size but no mention was made of the average volume of the testes they measured. The smaller the testis the more the overestimation and vice versa, thus mention of the mean size of the testes measured would have been most appropriate.5,25,26,31,63
In this study it was found that Prader orchidometer volume measurements correlated strongly with the actual testicular volumes measured by water displacement using Pearson correlation coefficient
(r=0.921,P=0.0001). There is no consensus by previous studies on whether or not Prader orchidometer measurements correlate with actual testicular volume measurements. While some say it correlates strongly, others say it does not.27,28,66 Sakamoto et al28 found a strong correlation between the two
(r=0.818, p=0.0001) though lower than what was got in this study. Paltiel et
51
al27 on the other hand did not find a statistically significant correlation between
Prader orchidometer and actual testicular volumes (r2=0.14, p=0.12).
Though they worked on animals and did not use the actual volume but a derived one like the one highlighted above, all these go to show the variability in the results produced by Prader orchidometer.
ACCURACY OF ULTRASOUND
All the ultrasound formulas in this study underestimated the actual testicular volume. Formula 1 (LWHx0.52) underestimated the actual testicular volume by 2.97ml (28.04%), formula 2 (LW2x0.52) by 4.08ml(38.54%) and formula 3 (LWHx0.71) by 0.41(3.89%). This means that formula 3 was the most accurate of the three ultrasound formulas in this study.
Sakamoto et al28 in their work found that ultrasound formula 1 underestimated by 1.9ml (21.3%), formula 2 underestimated by 3.35ml
(37.6%) and formula 3 overestimated by 0.8ml(7.46%). Though slightly different from this study, they also noted the most accurate formula to be formula 3. The slight difference in level of underestimation by ultrasound scan in these two studies could be accounted for by the difference in the actual testicular volume measured by water displacement (10.59ml in this study and
9.27ml by Sakamoto et al28). In addition, noticing that the result of the three formulas from the two studies vary by a range of 0.39ml to 1.07ml (1.07ml for formula 1, 0.73ml for formula 2 and 0.39 for formula 3) all within the confines of the mean difference in actual testicular volume between the two studies may mean the difference is only minimal.
52
Another reason could be the difference in sample size. They studied 40 testes while I studied 121testes.
Hsieh et al66 got 3.3ml ( 31.4%), 1.8ml (17.2%) and 0.6ml (6.3%) for formula 1, formula 2 and formula 3 respectively. Their mean actual testicular volume is the same with that of this study (10.6ml).The difference being
0.33mls for formula 1, 2.28ml for formula 2 and 0.2ml for formula 3. Except for formula 2, the difference in the two studies is less than 0.5ml, that is approximately 3%. This could be from the operator factor of the ultrasound.
Paltiel et al27 in their work on canine testes also noted that the most accurate of the ultrasound formulas was formula 3. In their work, formula1 underestimated by 1.9ml (31%) and formula 2 by 1.1ml (11%) and they noted that formula 3 caused the least mean bias but did not give the value.
Rivkees et al25 in their earlier work in1987 when the best formula was not an issue, used only formula 2 on 10 calves and 9 dogs with a simulated scrotum. They found that this formula had an accuracy of 4.6% + 1.6%. This is however not consistent with any of the studies mentioned earlier. This may be because they worked on scrotum that was simulated by double sheep skin.
In this study, it was also found that the ultrasound results correlated strongly with the actual testicular volume, which is in keeping with what other workers had reported.
Thus, all the previous works where all the three formulas were used were unanimous in the superiority of formula 3 and the strong correlation of all ultrasound formulas with the actual testicular volume.
53
RELATIONSHIP BETWEEN ULTRASOUND AND PRADER
ORCHIDOMETER.
Orchidometer in this study always overestimated the testicular volume measured by ultrasound, which is similar to what some studies had reported.27-31,63-65. It also has a strong correlation with all the three ultrasound formulas. Schiff et al24 however think orchidometer is as accurate as ultrasound when the orchidometer is used by an experienced practitioner. In their study, though the mean testicular volume by ultrasound and Prader orchidometer were the same, the correlation coefficient of r2= 0.52 and 0.48 for right and left testis respectively is low compared to other study.27,28,66. This means there is no consistency in the estimation by orchidometer for individual testis. Some overestimated while some underestimated so cancelling out to give equal mean testicular volumes. The paired t test significance is also very high (p= 0.49 and 0.81 for right and left testes respectively) as against this study where p= 0.0001.
As counseled by Tatsunami et al,64 proper standardization of the
Prader orchidometer measurement technique such as periodic comparison with ultrasonography results will be necessary to improve accuracy.
Suffice it to say that an instrument like the Prader orchidometer which gives a range of overestimation of between 15% and 87.1% in just four studies leaves much to be desired. This makes it difficult to recommend its use for measuring testes when minute details are expected as is required occasionally for evaluation of varicoceles.
54
CHAPTER SEVEN
CONCLUSION
Ultrasonography is more consistent in measuring testicular volume compared to Prader orchidometer. In this regard, the formula length x width x height x 0.71 is the most accurate formula for measuring testicular volume and has shown reproducibility . Though orchidometer correlates strongly with actual testicular volume, its values vary too widely between examiners
RECOMMENDATIONS
From the results obtained in this study, it is recommended that
1. When accurate assessment of testicular volume is necessary, ultrasound
scans with the formula; length x width x height x 0.71 should be used.
2. When only qualitative assessment is required, Prader orchidometer can be
used because of the cost of ultrasound.
3. To make the accuracy of orchidometer measurement better, urologists
should regularly compare their results with that obtained with ultrasound
formula 3.
4. Currently most ultrasound machines give testicular volume automatically
using the formula length x width x height x 0.52. The formula length x
width x height x 0.71 should now be the accepted norm and should be
inbuilt in the ultrasound software.
55
REFERENCES
1. Wikipedia contributors. Testicles (home page on Internet). Wikipedia, The
Free Encyclopedia;2009 April 20, 10:09UTC ( cited 2009 April 20).
Available
from:http://en.wikipedia.org/w/index.php?title=Testicle&oldid=284985007
2. Turek PJ. Male infertility. In: Tanagho EA, McAninch JW, editors. Smith’s
General Urology. 17th ed. USA: McGraw-Hill companies inc; 2008.p. 687-
717
3. Sigman M, Jarrow JP. Male infertility. In: Walsh PC., Retic AB., Vaughan
ED, Wein AJ, editors. Campbell’s Urology. 8th ed. Philadelphia: Saunders;
2002.p. 1474-1531
4. Lipshultz L, Corriere J. Progressive testicular atrophy in the varicocele
patient. J Urol. 1977; 117: 175–176.
5. Sakamoto H, Ogawa Y, Yoshida H. Relationship between testicular
volume and testicular function: comparison of the prader orchidometric
and ultrasonographic measurements in patients with infertility. Asian J
Androl. 2008; 10 (2): 319–324
6. Arai T, Kitahara S, Horiuchi S, Sumi S, Yoshida K. Relationship of
testicular volume to semen profiles and serum hormone concentrations in
infertile Japanese males. Int J Fertil Womens Med. 1998 ;43(1):40-47
7. Lenz S, Thomsen JK, .Giwercman A, Hertel NT, Hertz J, Skakkebaek NE.
Ultrasonic texture and volume of testicles in infertile men. Hum Reprod.
1994; 9 (5): 878-881
8. Sakamoto H, Yajima T, Nagata M, Okumura T, Suzuki K, Ogawa Y.
Relationship between testicular size by ultrasound and testicular function: 56
measurement of testicular length , witdth, and depth in patients with
infertility. Inter J Urol. 2008; 15: 529–533
9. Costabile RA, Skoog S, Radowich M. Testicular volume assessment in the
adolescent with a varicocele. J Urol. 1992; 147: 1348-1350
10. Sayfan J, Siplovich L, Koltun L, Benyamin N. Varicocele treatment in
pubertal boys prevents testicular growth arrest. J Urol. 1997;157: 1456-
1457
11. Paduch DA, Niedzielski J. Repair versus observation in adolescent
varicocele: a prospective study. J Urol. 1997; 158: 1128–1132
12. Sakamoto H, Ogawa Y, Yoshida H. Relationship between testicular
volume and varicocele in patients with infertility. Urology. 2008; 71: 104-
109
13. Salzhauer EW, Sokol A, Glassberg KI. Paternity after adolescent
varicocele repair. Pediatrics. 2004;114:1631-1633
14. Osifo OD, Evbuomwan I. Undescended testes in a developing country: A
study of the management of 71 patients. African Journal of urology. 2008;
5(1): 11-14
15. Zucchi A, Mearini L, Mearini E, Fioretti F, Bini V, Porena M. Varicocele
and Fertility: Relationship between testicular volume and seminal
parameters before and after treatment. J Androl. 2006; 27: 548–551
16. Wu FCW, Brown DC, Butler GE, Stirling HF, Kelna CJH. Early morning
plasma testosterone is an accurate predictor of imminent pubertal
development in prepubertal boys .Clin Endocrinol Metab. 1993; 76: 26-31
17. Smyth CM, Bremner WJ. Klinefelter syndrome review article. Arch Intern
Med. 1998;158:1309-1314
57
18. Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic
features of patients with suspected klinefelter syndrome. J Androl. 2003;
24, (1): 41-48
19. Boisen E. Testicular size and shape of 47,xyy and 47,xxy men in a double-
blind, double-matched population survey. Am J Hum Gene. 1979;31:697-
703
20. Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WFJr.
Predictors of outcome of long-term GnRH therapy in men with idiopathic
hypogonadotropic hypogonadism . J Clin Endocrinol & Metab. 2002; 87(9):
4128-4136
21. Nachtigall LB, Boepple PA, Pralong FP, Crowley WF. Adult-onset
idiopathic hypogonadotropic hypogonadism — a treatable form of male
infertility. England journal of medicine. 1997; 336 (6):410-415
22. Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA et al.
Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med.
2007; 357 (9):863-873
23. Chipkevitch E .Clinical measurement of testicular volume in adolescents:
comparison of the reliability of 5 methods. J Urol .1996; 156(6): 2050-2053
24. Schiff JD, Li PS, Goldstein M. Correlation of ultrasonographic and
orchidometer measurements of testis volume in adults. BJU International.
2004; 93: 1015 – 1017
25. Rivkees SA, Hall DA, Boepple PA, Crawford JD. Accuracy and
reproducibility of clinical measures of testicular volume. Journal of
Paediatrics. 1987 ; 110 ( 6): 914-917
58
26. Takihara H, Sakatoku J, Fujii M, Nasu T, Cosentino MJ, Cockett AT.
Significance of testicular size measurement in andrology. I. A new
orchidometer and its clinical application. Fertil Steril. 1983; 39: 836–40
27. Paltiel HJ, Diamond DA, Di Canzio J, Zurakowski D, Borer JG, Atala
A.Testicular volume: comparison of orchidometer and US measurements
in dogs. Radiology. 2002; 222: 114–119.
28. Sakamoto H, Saito K, Oohta M, Inoue K, Ogawa Y, Yoshida H. Testicular
volume measurement: comparison of ultrasonography, orchidometry, and
water displacement. Urology. 2007; 69: 152–157.
29. Diamond DA, Paltiel HJ, Di Canzio J, Zurakowski D, Bauer SB, Atala A et
al. Comparative assessment of pediatric testicular volume: orchidometer
versus ultrasound. J Urol. 2000; 164:1111-1114
30. Al Salim A, Murchison PJT, Rana A, Elton RA, Hargreave TB. Evaluation
of testicular volume by three orchidometers compared with
ultrasonographic measurements. Br J Urol. 1995; 76:632-635
31. Shiraishi K, Takihara H, Kamiryo Y, Naito K. Usefulness and limitation of
punched-out orchidometer in testicular volume measurement. Asian J
Androl. 2005; 7 (1): 77–80
32. Fowler CG. Testis and scrotum. In: Russel RG, Williams N S, Bulstrode
CJK, editors. Bailey and Love’s Short practice of surgery. 24th ed. London:
Arnold; 2004.p.1403 -1416.
33. Tanagho EA; Anatomy of the genitourinary tract. In:Tanagho EA,
McAninch JW, editors. Smith’s General Urology. 17th ed. USA: McGraw-
Hill Companies; 2008.p. 13
59
34. Ellis H, editor. Clinical Anatomy; A Revision and Applied Anatomy for
Clinical Students . 9th ed. Oxford: Blackwell scientific Limited; 2002.p.127-
132
35. McMinn RMH, editor. Last’s Anatomy. 9th ed. London:Churchill
Livingstone Publishers; 1994.p. 305-309.
36. Rundle AT, Sylvester PE. Measurement of testicular volume its application
to assessment of maturation, and its use in diagnosis of hypogonadism.
Arch Dis Child. 1962; 37: 514-517
37. Kuijper EAM, van Kooten J , Verbeke JIML, van Rooijen M, Lambalk CB.
Ultrasonographically measured testicular volumes in 0- to 6-year-old boys.
Hum Reprod. 2008;23,(4): 792–796
38. Andersson AM, Toppari J, Haavisto AM, Petersen JH, Simell T, Simell O,
Skakkebaek NE. Longitudinal reproductive hormone profiles in infants:
peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin
Endocrinol Metab. 1998;83:675–681
39. Main KM, Schmidt IM, Skakkebaek NE. A possible role for reproductive
hormones in newborn boys: progressive hypogonadism without the
postnatal testosterone peak. J Clin Endocrinol Metab. 2000; 85: 4905–
4907
40. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin
deficiency in the male infant. J Clin Endocrinol & Metab. 2005;90(5): 3122-
3127
41. Rey RA, Campo SM, Bedecarras P, Nagle CA, Chemes HE. Is infancy a
quiescent period of testicular development? Histological, morphometric,
60
and functional study of the seminiferous tubules of the cebus monkey from
birth to the end of puberty. J Clin Endocrinol Metab. 1993;76:1325–1331.
42. Handelsman DJ, Staraj S. Testicular size: the effect of aging, malnutrition,
and illness. J Androl. 1985; 6 : 144–151
43. Mahmoud AM, Goemaere S, El-Garem Y, Van Pottelbergh I, Comhaire
FH, Kaufman JM. Testicular volume in relation to hormonal indices of
gonadal function in community-dwelling elderly men. J Clin Endocrinol
Metab. 2003; 88:179–184.
44. Johnson L, Petty CS, Neaves WB. Age-related variation in seminiferous
tubules in men; a stereologic evaluation. J Androl. 1986; 7:316-322.
45. Raji AO., Igwebuike JU, Aliyu J. Testicular biometry and its relationship
with body weight of indigenous goats in a semi arid region of Nigeria.
Journal of Agricultural and Biological Science. 2008; 3(4): 6-8
46. Ku JH, Kim ME, Jeon YS, Lee NK, Park YH. Factors influencing testicular
volume in young men: results of a community-based survey. BJU Int.
2002; 90: 446–450.
47. Sobowale OB, Akiwumi O. Testicular volume and seminal fluid profile in
fertile and infertile males in Ilorin, Nigeria. Int J Gynaecol Obstet. 1989;
28(2):155-161
48. Main KM, Toppari J, Suomi AM, Kaleva M, Chellakooty M, Schmidt IM et
al. Larger testes and higher inhibin B levels in Finnish than in Danish
newborn boys. J Clin Endocrinol Metab. 2006;91:2732–2737.
49. Jensen TK, Jorgensen N, Punab M, Haugen TB, Suominen J, Zilaitiene B
et al. Association of In Utero Exposure to Maternal Smoking with Reduced
Semen Quality and Testis Size in Adulthood: A Cross-Sectional Study of
61
1,770 Young Men from the General Population in Five European
Countries. Am J Epidemiol. 2004;159:49–58
50. Pasqualotto FF, Lucon AM, De Goes PM, Sobreiro BP, Hallak J,
Pasqualotto EB, Arap S. Semen profile, testicular volume, and hormonal
levels in infertile patients with varicoceles compared with fertile men with
and without varicoceles. Fertil Steril. 2005; 83: 74–77
51. Thomas JC, Elder JS. Testicular growth arrest and adolescent varicocele:
does varicocele size make a difference? J Urol. 2002;168:1689-1691.
52. Osifo OD, Agbugui JO. Male infertility secondary to varicocele: a study of
the management of 45 patients. African Journal of Reproductive Health.
2008;12(1): 54-59
53. Sakamoto H, Katsuyuki S, Ogawa Y, Yoshida H. Effects of varicocele
repair in adults on ultrasonographically determined testicular volume and
on semen profile. Urology. 2008;71:485–489.
54. Rajeev K 1, Rupin S. Varicocele and male infertility:current status. J
Obstet Gynecol India. 2005; 55(6): 505-516
55. Mieusset R., Bujan L., Massat G, Mansat A, Pontonnier F. Clinical and
biological characteristics of infertile men with a history of cryptorchidism.
Hum Reprod.1995; 10: 613-619.
56. Lee PA, Coughlin MT, Bellinger MF. No relationship of testicular size at
orchiopexy with fertility in men who previously had unilateral
cryptorchidism. J Urol. 2001;166: 236–239
57. Kojima Y, Hayashi Y, Mizuno K, Kurokawa S, Sasaki S, Kohri K.
Assessment of serum follicle-stimulating hormone level and testicular
62
volume for prediction of paternity potential in pubertal boys who underwent
bilateral orchiopexy in childhood. J Urol. 2006 ;175: 2290-2294
58. Jarow JP, ISharlip ID, Belker AM, Lipshultz LI, Sigman M, Thomas AJ et
al. Best practice policies for male infertility. J Urol. 2002; 167: 2138–2144.
59. Sakamoto H, Ogawa Y. Does a clinical varicocele influence the
relationship between the testicular volume by ultrasound and the testicular
function in patients with infertility? Fertil Steril.2008;
doi;10:1016/J.Fertnstert.2008.08.105.
60. Blondell RD, Foster MB, Dave KC. Disorders of puberty American Family
Physician. 1999;60(1): 209-224
61. Chipkevitch Eugenio. Clinical assessment of sexual maturation in
adolescents. J Pediatr . 2001;77(Supl.2):135-142
62. Taskinen S, Taavitsainen M, Wikstrom S. Measurement of testicular
volume: comparison of 3 different methods. J Urol. 1996; 155: 930–933.
63. Sakomoto H, Saito K, Yoshio O, Yoshida H. Testicular volume
measurements using Prader orchidometer versus ultrasonography in
patiets with infertility. Urology. 2007; 69: 158-162
64. Tatsunami S, Matsumiya K, Tsujimura A, Itoh N, Sasao T, Koh E et al.
Inter/intra investigator variation in orchidometric measurements of
testicular volume by ten investigators from five institutions. Asian J Androl.
2006; 8 (3): 373–378
65. Karaman MI, Kaya C, Caskurlu T, Guney S, Ergenekon E. Measurement
of pediatric testicular volume with Prader orchidometer: comparison of
different hands. Pediatr Surg Int. 2005; 21: 517–520
63
66. Hsieh M, Huang S, Huang H, Chen Y, Hsu Y. The reliability of
ultrasonographic measurements for testicular volume assessment:
comparison of three common formulas with true testicular volume. Asian J
Androl. 2009; 11: 261–265
67. Araoye OM. Research methodology with statistics for health and social
sciences. Ilorin: Nathadex Publishers; 2004.p. 115-121.
68. Ukoli F, Osime U, Akereyeni F, Okunzuwa O, Kittles R, Adams-Campbell
L. Prevalence of elevated serum prostate specific antigen in rural Nigeria.
Int J Urol. 2003;10(6): 315- 322.
69. Ogunbiyi JO, Shittu OB. Increased incidence of prostate cancer in
Nigerians .J Natl Med Assoc. 1999;91:159-164.
64
APPENDIX 1
Prader Orchidometer
65