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ORIGINAL ARTICLE
Year : 2018  |  Volume : 21  |  Issue : 1  |  Page : 1-5

Hyperprolactinemia and female infertility: Pattern of clinical presentation in a tertiary health facility in Northern Nigeria


1 Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Obstetrics and Gynaecology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Web Publication21-May-2018

Correspondence Address:
Dr. Idris Ainavi Isah
Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, P. O. Box 06, Shika, Zaria
Nigeria
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DOI: 10.4103/smj.smj_69_15

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  Abstract 


Background: Hyperprolactinemia is an extremely common disorder, especially among reproductive age women, affecting about one-third of infertile females. There is a paucity of data on the pattern of clinical presentation of hyperprolactinemia among infertile female patients in Nigeria. This study, therefore, aimed to determine the pattern of clinical presentation of hyperprolactinemic infertile female patients in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Northern Nigeria. Materials and Methods: Blood sample of 120 infertile female patients aged 15–45 years attending the infertility clinic at ABUTH over 9 months was taken. Data on clinical signs and symptoms were collected using interview-administered questionnaire. Serum prolactin was assayed by microwell enzyme-linked immunosorbent assay technique based on the noncompetitive sandwich principle. Data obtained were analyzed using SPSS version 20 (Syntron Bioresearch. Inc. California, United States of America (USA)). Results: The mean serum level of prolactin concentration at presentation was 31 ng/ml (range, 2.5–109 ng/ml). Sixty-two patients (51.7%) had hyperprolactinemia and 58 (48.3%) had normal prolactin level. The majority of those with hyperprolactinemia 58.6% were in the 25–34 years' age group. Of those with hyperprolactinemia, majority (27.4%) presented with galactorrhea and others presented with symptoms such as menstrual abnormalities, recurrent abortion, hirsutism, and mixed presentations. However, 25.8% of them were symptomless. Conclusion: Galactorrhea was the most common mode of presentation among infertile hyperprolactinemic females in ABUTH, and a larger proportion were symptomless.

Keywords: Female infertility, galactorrhea, hyperprolactinemia


How to cite this article:
Isah IA, Aliyu IS, Yusuf R, Isah H S, Randawa A J, Adesiyun A G. Hyperprolactinemia and female infertility: Pattern of clinical presentation in a tertiary health facility in Northern Nigeria. Sahel Med J 2018;21:1-5

How to cite this URL:
Isah IA, Aliyu IS, Yusuf R, Isah H S, Randawa A J, Adesiyun A G. Hyperprolactinemia and female infertility: Pattern of clinical presentation in a tertiary health facility in Northern Nigeria. Sahel Med J [serial online] 2018 [cited 2018 Aug 19];21:1-5. Available from: http://www.smjonline.org/text.asp?2018/21/1/1/232786




  Introduction Top


Endocrine disorders are common worldwide affecting up to 14% of couples.[1],[2] Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult female population to as high as 9%–17% in female population with reproductive health disorders.[3],[4] The diagnosis of hyperprolactinemia is made when serum prolactin levels are found on two different occasions to be above the upper limits of the established population reference range (usually 20–25 ng/ml) or when the levels of prolactin are increased once with symptoms suggestive of hyperprolactinemia.[5] The etiology of hyperprolactinemia may be physiological, pharmacological, or pathological. Drugs that stimulate the hypothalamic dopamine system and/or pituitary or dopamine receptors can result in an elevated prolactin.[5],[6]

Prolactinomas account for 25%–30% of functioning pituitary tumors and are the most frequent cause of chronic hyperprolactinemia.[7] Pathological hyperprolactinemia can also be caused by nonhypothalamic-pituitary disease.

About 40% of patients with primary hypothyroidism have mild elevation of prolactin levels that can be normalized by thyroid hormone replacement.[5] About 30% of patients with chronic renal failure and up to 80% of patients on hemodialysis have elevated prolactin levels.[8]

The clinical presentations of hyperprolactinemia result from the hormonal influence on prolactin target tissue, which are predominantly the reproductive systems and breast tissue. Hyperprolactinemia is typically identified through a combination of these clinical symptoms and a quantitative serum prolactin immunoassay. The clinical symptoms include galactorrhea, diminished fertility, menstrual abnormalities, recurrent abortions, hirsutism, and osteopenia.[9],[10],[11],[12] There is a paucity of local data about the pattern of clinical presentation of hyperprolactinemia in Nigeria, including Zaria. Therefore, this study aimed to determine the presenting pattern of hyperprolactinemia in infertile females attending infertility clinic at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Northern Nigeria.


  Materials and Methods Top


This study was a descriptive cross-sectional study. A total of 120 infertile female participants in the reproductive age group of 15–45 years were recruited for the study over a period of 9 months. They were from among the females attending the infertility clinic of ABUTH, Zaria. They all have medical history of inability to conceive after 1 year despite regular and unprotected sexual intercourse.

Ethical approval was obtained from the Ethical and Scientific Committee, ABUTH, Zaria 17th February 2010. Informed and written consent was obtained from the participants, and information regarding the medical history and physical examinations of the selected participants were also obtained using interviewer-administered questionnaires. Infertile females who were below 15 years and above 45 years of age, those on hormonal therapy, those who had male factors as a cause of their infertility, and those who declined to give consent were excluded from the study.

Participants with regular menstrual cycles were instructed to come for sampling on the 2nd or 3rd day of their menstrual period (follicular phase), after an overnight fast of 8 to 12 hours. Random samples were collected from participants presenting with amenorrhea or irregular menstrual cycles after an overnight fast as above and after haven't ruled out pregnancy as a cause of their amenorrhea. A 5ml syringe and needle was used to collect 3ml of whole blood specimen from the ante-cubita vein into a plain specimen bottle after disinfection of the venepuncture site.

The serum prolactin was quantitated with the reagent kits obtained from Syntron Bioresearch (California, USA) using ELISA technique.

The normal reference range used for the study is 8–22 ng/ml (Chemical Pathology Laboratory ABUTH, Zaria) using the same reagent kits. Hyperprolactinemia was categorized as mildly elevated (23–100 ng/ml), moderately elevated (101–200 ng/ml), high (201–1000 ng/ml), and very high (>1000 ng/ml).[13],[14],[15]

The intra-assay variance of this test has coefficient of variation (CV) of 3% and CV for the inter-assay variance was 3.5%.


  Results Top


The total number of infertile patients successfully evaluated was 120 females, out of which 62 (51.7%) had hyperprolactinemia as shown in [Table 1]. A higher percentage of hyperprolactinemic patients with secondary infertility (72.0%) were observed compared to those with primary infertility (28%) as presented in [Table 2].
Table 1: Prevalence of hyperprolactinemia among the infertile females studied

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Table 2: Distribution of hyperprolactinemic females in relation to the type of infertility

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Sixty (96.8%) hyperprolactinemic females had mild hyperprolactinemia, 2 (3.2%) had moderate hyperprolactinemia, while none had high or very high levels of hyperprolactinemia as shown in [Table 3].
Table 3: Distribution of hyperprolactinemic females according to their serum prolactin levels

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Distribution of hyperprolactinemic females according to the age group at presentation shows that the largest proportion of them (58.6%) was in the 25–34 years' age group while the lowest proportion (10.6%) was in the 15–24 years' age group as presented in [Table 4].
Table 4: Age distribution of infertile female with hyperprolactinemia

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The clinical presentation of those with hyperprolactinemia included galactorrhea which formed the majority with 27.4%, menstrual abnormalities 12.9%, recurrent abortion 9.7%, hirsutism 4.8%, and mixed presentations 19.4%. However, 25.8% of them were symptomless as presented in [Table 5].
Table 5: Incidence of various clinical symptoms in hyperprolactinemic females

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  Discussion Top


The prevalence of hyperprolactinemia in this study was 51.7% among the infertile females. This prevalence rate is higher than 37%, 33%, and 31.6%, respectively, that was reported for Lagos, Maiduguri, and Egypt.[16],[17] These differences might be due to different study populations with different underlying etiological factors. However, the prevalence rate in this study was similar or close to that obtained in Kano with the prevalence rate of 48%[18] and Southampton in the United Kingdom.

In this study, serum prolactin level was mildly elevated in 96.8% of the patients and moderately elevated in 3.2% of the patients. These differ from the finding of Randal et al.,[13] who found 61.8% of the patients to have moderately elevated prolactin level and 39% of them had highly elevated levels of prolactin.

In the present study, the incidence of hyperprolactinemia with high or very high prolactin level was virtually zero, suggesting that the incidence of prolactinoma (microadenoma and macroadenoma) among the infertile females was very rare as demonstrated by Nadeem [19] who showed a strong association of microadenoma with highly elevated level of prolactin and macroadenoma with very highly elevated levels of prolactin.

The majority of the infertile females with hyperprolactinemia (58.6%) were aged 25–34 years. This finding suggests that most infertile females with hyperprolactinemia were in their mid-reproductive age. This may probably be due to the fact that majority of the infertile females present mostly during their mid-reproductive age after they might have sought for nonorthodox means to find solution to their infertility during their early reproductive age and probably those in their late reproductive age did not border much to seek for orthodox means of treatment.

This study shows that the minimum age of hyperprolactinemic females at presentation is 15 years and the maximum age at presentation is 44 years. This is similar to the finding of Vane and Thornier [15] who also found that at the time of diagnosis in their center, most females were between 15 and 45 years of age.

Most of the infertile females with hyperprolactinemia (72%) presented with secondary infertility. This may be attributed to the fact that the major cause of infertility in African women is due to the damage to  Fallopian tube More Details function which usually occurs following pelvic inflammatory disease, postabortal sepsis, and puerperal complications, and hence, majority of the infertile females present with secondary infertility.[20] Moreover, there may be proportional increase in the incidence of those with hyperprolactinemia among those with secondary infertility as observed in the present study.

This study demonstrated that the most common clinical presentations of hyperprolactinemia among infertile females were galactorrhea, recurrent abortion, and menstrual abnormalities while almost a quarter were symptomless. This differs slightly from the studies of Akbar [21] in North West of Iran which reveals that the most common clinical presentations of hyperprolactinemia among infertile women were menstrual abnormalities and galactorrhea.[21] These clinical presentations may have resulted from the hormonal influence of prolactin on its target tissues which are predominantly the reproductive systems and breast tissue.[22] Other symptoms such as hirsutism may be a sign of chronic hyperandrogenism possibly due to increased dehydroepiandrosterone sulfate secretion induced by prolactin from adrenal glands through ACTH.[23]

The presence of symptom of hyperandrogenism such as hirsutism in this study may also suggest that hyperprolactinemia probably coexists with some other hormonal abnormalities such as polycystic ovarian syndrome. This may account for the possibility of multiple endocrine disorders in some of the infertile females with hyperprolactinemia. Prolonged hypoestrogenism induced by hyperprolactinemia might have caused the recurrent abortion seen in this study. It may sometimes cause osteopenia.

In this study, about a quarter of the infertile females had no significant signs and symptoms, suggesting that hyperprolactinemia in these patients may probably be as a result of macroprolactinemia. Macroprolactinemia is the apparent increase in serum prolactin without signs and symptoms. This form of macroprolactin is unable to bind to prolactin receptors and exhibits no systemic response because macroprolactin is not biologically active and in some respects is a laboratory artifact. It has been advocated that a screening test should be applied to all samples with increased total serum prolactin to detect the presence of macroprolactin using gel filtration chromatography or polyethylene glycol precipitation methods as hyperprolactinemia attributable to macroprolactin is a frequent cause of misdiagnosis and mismanagement of patients.


  Conclusion Top


Galactorrhea was the most common mode of presentation among infertile hyperprolactinemic females in ABUTH, Zaria, and a larger proportion were symptomless.

Recommendations

Considering the high prevalence of those who are symptomless which may probably be due to macroprolactinemia, it is advisable for physicians in this environment to consider testing for macroprolactinemia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
WHO. Infertility: A Tabulation of Available Data on Prevalence of Primary and Secondary Infertility. Geneva: WHO; 1991. p. 1-15.  Back to cited text no. 1
    
2.
Mosher WD, Pratt AF. Fecundity and Infertility in the United Sates 1965–1982. Vol. 104. Unite State of America: National Centre for Health Statistics (Advance data); 1985. p. 140.  Back to cited text no. 2
    
3.
Biller BM, Luciano A, Crosignani PG, Molitch M, Olive D, Rebar R, et al. Guidelines for the diagnosis and treatment of hyperprolactinemia. J Reprod Med 1999;44:1075-84.  Back to cited text no. 3
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4.
Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, et al. Guidelines of the pituitary society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 2006;65:265-73.  Back to cited text no. 4
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Luciano AA. Clinical presentation of hyperprolactinemia. J Reprod Med 1999;44:1085-90.  Back to cited text no. 5
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Molitch ME. Drugs and prolactin. Pituitary 2008;11:209-18.  Back to cited text no. 6
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Webster J, Scanlon MF. Prolactinomas. In: Sheaves R, Jenkins PJ, Wass JA, editors. Clinical Endocrine Oncology. Oxford, UK: Blackwell Science; 1997. p. 189-94.  Back to cited text no. 7
    
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Abha Majumdar and Nisha Sharma Mangal, Hyperprolactinemia J Hum Reprod Sci 2013;6:168-75.  Back to cited text no. 8
    
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Molitch ME. Disorders of prolactin secretion. Endocrinol Metab Clin North Am 2001;30:585-610.  Back to cited text no. 9
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Klibanski A, Neer RM, Beitins IZ, Ridgway EC, Zervas NT, McArthur JW, et al. Decreased bone density in hyperprolactinemic women. N Engl J Med 1980;303:1511-4.  Back to cited text no. 12
    
13.
Randall RV, Laws ER Jr., Abboud CF, Ebersold MJ, Kao PC, Scheithauer BW, et al. Transsphenoidal microsurgical treatment of prolactin-producing pituitary adenomas. Results in 100 patients. Mayo Clin Proc 1983;58:108-21.  Back to cited text no. 13
    
14.
Aron DC, Tyrrell JB, Wilson CB. Pituitary tumors. Current concepts in diagnosis and management. West J Med 1995;162:340-52.  Back to cited text no. 14
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15.
Vance ML, Thorner MO. Prolactin: Hyperprolactinemic syndromes and management. In: DeGroot LJ, Besser M, Burger HG, (eds). Text book of endocrinology. Philadelphia: W.B. Saunders Co., 1995. p. 394-401.  Back to cited text no. 15
    
16.
Kuku SF, Akinyanju PA, Ojeifo JO. Serum levels of gonadotropins, prolactin, and progesterone in infertile female Africans. Int J Fertil 1987;32:393-8.  Back to cited text no. 16
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Iris A, Kawuwa MB, Habu SA, Adebayo A. Prolactin levels among infertile women in Maiduguri, Nigeria. Trop J Obstet Gynaecol 2003;20:97-100.  Back to cited text no. 17
    
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Emokpae MA, Uadia PO, Mohammed AZ. Hormonal evaluations and endometrial biopsy in infertile women in Kano, Northern Nigeria: A comparative study. Ann Afr Med 2005;4:99-103.  Back to cited text no. 18
    
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Nadeem A, Arshad Q. Hyperprolactinaemia in Non Lactating Women in Islamabad and Lahore. Unpuplished Thesis, Department of Biological Sciences/Quaid-i-Azam University Islamabad; 2004.  Back to cited text no. 19
    
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Ericksen K, Brunette T. Patterns and predictors of infertility among African women: A cross-national survey of twenty-seven nations. Soc Sci Med 1996;42:209-20.  Back to cited text no. 20
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Glickman SP, Rosenfield RL, Bergenstal RM, Helke J. Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women. J Clin Endocrinol Metab 1982;55:251-7.  Back to cited text no. 23
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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