|Year : 2017 | Volume
| Issue : 2 | Page : 55-59
Prevalence of hyperprolactinemia among infertile patients with menstrual abnormalities and/or galactorrhea at a University Teaching Hospital, North West Nigeria
Tajudeen Akande1, Adebiyi Gbadebo Adesiyun2, Sambo Aliyu3, Abdullahi Randawa2
1 Department of Obstetrics and Gynaecology, Rasheed Shekoni Specialist Hospital, Dutse, Jigawa State, Nigeria
2 Department of Obstetrics and Gynaecology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
3 Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
|Date of Web Publication||30-Apr-2018|
Dr. Adebiyi Gbadebo Adesiyun
Department of Obstetrics and Gynaecology, Ahmadu Bello University Teaching Hospital, Zaria
Source of Support: None, Conflict of Interest: None
Objective: Hyperprolactinemia may be associated with galactorrhea, menstrual abnormalities, and infertility. When diagnosed and appropriate treatment instituted, there may be early relief of these symptoms and pregnancy rate may increase. This study determined the prevalence of hyperprolactinemia among infertile patients with menstrual abnormalities and/or galactorrhea. Patients and Methods: A cross-sectional study of women attending the infertility clinic who had galactorrhea and/or menstrual abnormalities. Menstrual abnormalities for this study refer to those with oligomenorrhea and amenorrhea. Results: Out of the 207 women studied, 75 of them have hyperprolactinemia, giving a prevalence of 36.2%. Galactorrhea has higher sensitivity (68%), a higher positive predictive value (39.5%), and a higher negative predictive value (69.3%) when compared with menstrual abnormalities which had sensitivity of 44%, positive predictive value of 29.7%, and negative predictive value of 56.3%, respectively. They, however, have the same specificity of 40.9%. Conclusion: The prevalence of hyperprolactinemia is high in this study. Galactorrhea is a better clinical indicator of hyperprolactinemia when compared with menstrual abnormalities.
Keywords: Galactorrhea, hyperprolactinemia, infertility, menstrual abnormality, prevalence
|How to cite this article:|
Akande T, Adesiyun AG, Aliyu S, Randawa A. Prevalence of hyperprolactinemia among infertile patients with menstrual abnormalities and/or galactorrhea at a University Teaching Hospital, North West Nigeria. Arch Med Surg 2017;2:55-9
|How to cite this URL:|
Akande T, Adesiyun AG, Aliyu S, Randawa A. Prevalence of hyperprolactinemia among infertile patients with menstrual abnormalities and/or galactorrhea at a University Teaching Hospital, North West Nigeria. Arch Med Surg [serial online] 2017 [cited 2019 Mar 23];2:55-9. Available from: http://www.archms.org/text.asp?2017/2/2/55/231627
| Introduction|| |
Infertility is common worldwide, occurring in about one in ten couples. The prevalence of infertility is particularly high in sub-Saharan Africa ranging from 20% to 46% in some parts of West Africa , and accounts for 45%–65% of gynecological consultation., The high premium placed on children, especially in the African society, contributes in no small way to the great emotional and psychological stress on the couples affected with problems of infertility. These burden may even be more in setting that treat infertile women as outcast, and in the event of demise of the husband, she has no claims to his estate. Infertility is a major cause of marital disharmony in Africa, and it exposes women to expulsion from the community, social discrimination, and physical violence.
Elevated prolactin (PRL) levels are one of the causes of infertility, and it can result from physiological causes, such as pregnancy and stress, and chronic use of some pharmacological agents such as neuroleptics, antidepressants, estrogens, opiates, antihypertensive drugs, antiandrogens, H2-receptor antagonists, anticonvulsants, and cholinomimetics. Pathological causes including that due to prolactinoma are another major cause of elevated serum PRL. Hyperprolactinemia inhibits ovarian steroidogenesis. PRL hypersecretion profoundly affects reproductive function. At the level of the hypothalamus, elevated PRL levels, by a short loop feedback, stimulate dopamine receptors and dopamine secretion which results in abnormalities in the frequency and amplitude of gonadotropin-releasing hormone pulsations, perhaps by altering adrenaline secretion. The resultant effect is inhibition in the release of gonadotropins (follicle-stimulating hormone and luteinizing hormone [LH]) even though there is no interference with their synthesis.
In the pituitary gland, hyperprolactinemia has a direct inhibitory effect on LH secretion by interfering with the positive estrogen effect on the mid-cycle LH surge that triggers ovulation. In the ovary, PRL directly inhibits basal as well as gonadotropin-mediated estradiol and progesterone production and ovulation. It does this by inhibiting LH-induced production of plasminogen activator in preovulatory follicles which reduces the availability of plasmin. Plasmin is necessary for the digestion of the follicle wall that results in the release of the ovum. In sub-Saharan Africa, tubal factor is known to be a leading cause of female infertility, but in a study carried out in North-eastern Nigeria among women with infertility, hyperprolactinemia prevalence of 31.7% was reported. Could this be a pointer that the prevalence of hyperprolactinemia is on the rise among our women with infertility?
Hyperprolactinemia when diagnosed may be amenable to medical treatment over a short period of time and at a relatively affordable cost. Studies by Adesiyun et al. and several others confirmed the efficacy of dopamine agonists in not only high pregnancy and delivery rates among this group of patients but also improving their quality of life by relieving them of troublesome symptoms associated with hyperprolactinemia such as menstrual abnormalities and galactorrhea. The aim of this study was to determine the prevalence of serum hyperprolactinemia among infertile patients with menstrual abnormalities and/or galactorrhea. The study will also help answer the question, which is a better clinical indicator of hyperprolactinemia-galactorrhea or menstrual abnormalities?
| Patients and Methods|| |
The study was a cross-sectional study and the study participants were patients who presented with infertility and with symptoms of menstrual abnormalities and/or galactorrhea.
For the purpose of this study, the following definitions were adopted. Infertility was inability to conceive by a woman after 12 months of regular and unprotected intercourse. Oligomenorrhea was menstrual interval occurring at intervals of >35 days, with only 4–9 periods in 1 year in a previously normally menstruating woman. Amenorrhea was complete lack of menses or cessation of menses for 3 consecutive cycles or for a time of 6 months. Menstrual abnormalities for this study refer to oligomenorrhea and amenorrhea. Galactorrhea was diagnosed from history and physical examination. Hyperprolactinemia for this study was serum PRL level >35 ng/ml. Normal PRL level for this study was serum PRL between 5 and 35 ng/ml as determined by mini VIDAS PRL kits used.
- All consenting women who attended the infertility clinic and who had symptoms of menstrual abnormalities and/or galactorrhea
- All those who consented to come for follow-up were included in the study.
- All nonconsenting women
- All infertile women without symptoms of menstrual abnormalities and/or galactorrhea
- All those on treatment within the past 6 months with dopamine agonists
- All those on psychotropic drugs within the past 6 months were excluded from the study.
The recruitment and data collection was for over a 4-month period from January 2013 to April 2013. Patients who presented to the gynecologic clinic were informed of the study; informed written consent obtained and was recruited if consented and eligible for the study. Clinical examination was conducted in the patients.
Serum PRL was determined using the mini VIDAS automated machine which employs the enzyme-linked fluorescence assay technology; these combine the enzyme-linked immunosorbent assay test method with a final fluorescent reading. This technology ensures excellent result sensitivity and specificity. VIDAS automated machine and the reagent used were manufactured by Biomerieux SA, Chemin de l'orme, Marcy l'Etoile, France 69280. VIDAS automated machine does not differentiate between little PRL and the big big (macro-PRL) PRL. Furthermore, the mini VIDAS PRL kits (REF 30 410) that was used can only measure serum PRL with a range of 0–200 ng/ml. Any value above 200 would only read >200 except otherwise further diluted and re-run.
The indices of validity used to find out if galactorrhoea or menstrual abnormality is a better clinical indicator for hyperprolactinaemia were sensitivity, specificity, positive predictive value and negative predictive value. The formulae below were used to compute each index:
The diseases here are menstrual abnormalities and galactorrhea.
| Results|| |
A total of 207 consenting consecutive infertile women with menstrual abnormalities and/or galactorrhea attending the infertility clinic were recruited into the study. The ages ranged between 16 and 46 years with the mean of 29.7 years. Most of the participants were in the age group of 25–29 years (37.7%) while the age groups of 15–19 and >44 years were the least with 1.4%, respectively.
Majority of the participants were in their first order of marriage (82.6%), and only 13% were in the 2nd or more order of marriage. The prevalence of hyperprolactinemia from all the participants is 36.2% while 59.4% had normal PRL level. Only 4.3% of the participants had hypoprolactinemia.
Of the 111 patient with menstrual abnormalities, 33 had hyperprolactinemia; therefore, the prevalence of hyperprolactinemia among infertile women with menstrual abnormalities is 29.7% [Table 1]. The remaining patients with menstrual abnormalities had hypoprolactinemia (3 patients, 2.7%) and normal PRL level in 75 patients (67.6%). Among the 36 patients with amenorrhea, 17 had hyperprolactinemia, and the prevalence of hyperprolactinemia among those with amenorrhea is therefore 47.2%. Seventy-five patients had oligomenorrhea, of which 21 results showed high PRL level. The prevalence of hyperprolactinemia among those with oligomenorrhea is 28% [Table 2]. Fifty-one of the 129 patients with galactorrhea had hyperprolactinemia, and thus, the prevalence of hyperprolactinemia among infertile women with galactorrhea is 39.5%. Of the remaining patients, 6 (4.7%) and 72 (55.8%) have hypoprolactinemia and normal PRL levels, respectively [Table 3].
|Table 1: The relationship between menstrual abnormalities and prolactin levels in the participants|
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|Table 2: The relationship between amenorrhea oligomenorrhea and hyperprolactinemia|
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|Table 3: The relationship between galactorrhea and prolactin levels of the subjects|
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The sensitivity for both menstrual abnormalities and galactorrhea was the same, i.e. 40.9%.
However, the specificity, positive predictive value, and negative predictive value for galactorrhea were higher than for menstrual abnormalities. Galactorrhea had a higher sensitivity (68%), positive predictive value (39.5%), and negative predictive value (69.3%) as compared to that of menstrual abnormalities of 44%, 29.7%, and 56.3%, respectively. This implied that galactorrhea is a better clinical indicator of hyperprolactinemia than menstrual abnormalities [Figure 1].
|Figure 1: Validity tests for both menstrual abnormalities and galactorrhoea|
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Of the 19 that had serum PRL of 100 ng/ml and above, only 2 had skull X-ray features of pituitary enlargement, but 17 of the 19 had ophthalmic features of optic chiasm compression.
| Discussion|| |
From this study, the overall prevalence of hyperprolactinemia among all the participants was 36.2%. This is similar to the prevalence rate of 31.7% reported by Idrissa et al. in a study conducted at a university in the north west region of Nigeria and 41% reported by Prathibha et al. in a study done at Hyderabad, India. Other previous studies by Giwa-Osagie et al. and Kuku  had shown a high prevalence of hyperprolactinemia in infertile Nigerian women, findings that were in agreement with reports on infertile women from other populations of the world.,, However, the prevalence in this study was higher than that reported by Akande et al. who reported a prevalence of 12.3% in the study conducted at a university hospital in the south west region of Nigeria. This lower prevalence from the latter study is not surprising as the study was conducted among all women with infertility that may have other causes of the infertility. This study was restricted to infertile women with symptoms of menstrual abnormalities (amenorrhea and oligomenorrhea) and galactorrhea that may be associated with hyperprolactinemia.
The prevalence of hyperprolactinemia among infertile women with menstrual abnormality in this study was 29.7%; though this may appear high, it is lower than the overall prevalence in this study. Greer et al., however, reported even a lower prevalence of 15% among anovulatory women. This may be because high level of relatively inactive PRL in the absence of a tumor can be due to the circulation of macromolecules of PRL by anti-PRL., The upper limit of the normal range is often quoted as 36 ng/ml., As such in this study, the upper limit of normal range as determined by the VIDAS PRL kits (REF 30 410) used is 35 ng/ml.
The prevalence of hyperprolactinemia among those with amenorrhea in this study was 47.2%. This is higher than the general prevalence of those with menstrual abnormalities which consisted both of those with oligomenorrhea and amenorrhea. That of those with oligomenorrhea was 28%. This may infer that that hyperprolactinemia may be a major cause of amenorrhea most especially when the serum PRL is markedly elevated. The prevalence of hyperprolactinemia among infertile women with galactorrhea in this study was 39.2%. This is higher than that reported in a study conducted in Japan. Eftekhari et al. concluded in their study that hyperprolactinemia that presents a gynecological problem may or may not be accompanied by galactorrhea, and galactorrhea cannot be a certain index for hyperprolactinemia. Giwa-Osagie et al. in a study reported that 19.5% of hyperprolactinemic galactorrhea among those with 2° amenorrhea. Many women with galactorrhea do not have hyperprolactinemia, and the condition probably arises from the abnormal sensitivity of breast tissue to normal serum concentrations of PRL. Such women do not require further investigation of the pituitary, but if the galactorrhea is sufficiently embarrassing to warrant treatment, it usually responds to suppression of PRL with a dopamine agonist.
In this study, 19 of the 207 women studied had serum PRL above 100 ng/ml, and all of the 19 had galactorrhea with only 12 having menstrual abnormalities. The discrepancy between clinical and biochemical findings may sometimes be caused by measurement of biologically inactive but immunologically reactive hormone. The gold standard for detecting these macro-PRLs is gel-filtration chromatography, a procedure that allows for quantification of all three variants of PRL. Unfortunately, this method is labor intensive and not suitable for performance in routine laboratory analysis. In the alternative, precipitation with polyethylene glycol (PEG) is a widely used screening test for macro-PRL, and this can be relatively easily performed in clinical laboratories where a low PRL recovery after PEG treatment indicates the presence of macro-PRL.
Validity tests that were done by computing the validity of menstrual abnormality and galactorrhea, respectively, against the presence or absence of hyperprolactinemia as determined by the mini VIDAS kit (REF 30 410) used in this study demonstrate that galactorrhea is a better clinical indicator of hyperprolactinemia than symptoms of menstrual abnormalities.
Of the 19 that had serum PRL of 100 ng/ml and above, only 2 had skull X-ray features of pituitary enlargement. The low yield is not surprising as X-ray may not pick the pathology where the pituitary enlargement is not significant or if microadenoma. For this, MRI would be the most appropriate tool of investigation.
| Conclusion|| |
The breakdown of the prevalence of hyperprolactinemia among those with menstrual abnormalities revealed that those with amenorrhea had a much higher prevalence of 47.2% than those with oligomenorrhea which had 28%. All participants with serum PRL level ≥100 ng/ml had galactorrhea but not all had menstrual abnormalities. Galactorrhea was found to be a better clinical indicator of hyperprolactinemia.
From the overall prevalence of 36.2% of hyperprolactinemia among infertile women with symptoms of menstrual abnormalities and/or galactorrhea, it implies that hyperprolactinemia may be a major etiological contributor to infertility in these groups of patient and therefore merits routine serum PRL assay. However, since galactorrhea was found to be a better clinical indicator of hyperprolactinemia, it may serve as an guide to commence empirical treatment with dopamine agonists with proven efficacy, especially where assay of serum PRL is a challenge in low resource setting.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Cates W, Farley TM, Rowe PJ. Worldwide patterns of infertility: Is Africa different? Lancet 1985;2:596-8.
Belsey MA. The epidemiology of infertility: A review with particular reference to sub-Saharan Africa. Bull World Health Organ 1976;54:319-41.
Idrisa A, Ojiji E. Pattern of infertility in North Eastern Nigeria. Trop J Obstet Gynaecol 2000;17:27-9.
Otubu JA. Infertility. Trop J Obstet Gynaecol 1995;12:68-71.
Idrissa A, Kawuwa MB, Habu SA, Adebayo AA. Prolactin levels among infertile women in Maiduguri, Nigeria. Trop J Obst Gynae 2003;17:27-35.
Okonofua FE, Harris D, Odebiyi A, Kane T, Snow RC. The social meaning of infertility in South West Nigeria. Health Transit Rev 1997;7:205-20.
Torre DL, Falorni A. Pharmacological causes of hyperprolactinemia. Ther Clin Risk Manag 2007;3:929-51.
Hiralal Konar. Special topics. Textbook of Gynaecology. Ed; Dutta DC. Re-edited by Hiralal Konar. New Central Book Agency. Kolkata. 2009;33:548-9.
Klufo CA. Hyperprolactinaemia and prolactinomas. In: Comprehensive Gynaecology in the Tropics. Eds. Kwawukume EE, Emuveyan EE. Graphic Packaging Ghana. 2005. p. 375-81.
Megafu U, Okoye IJ, Ofodile A, Affam A. Therapeutic insemination of semen: Ultrasound monitoring of ovarian follicular growth. Orient J Med 1995;7:32-7.
Idrisa A, Kawuwa MB, Habu SA, Adebayo AA. Prolactin levels among infertile women in Maiduguri, Nigeria. Trop J Obstet Gynaecol 2003;17:27-9.
Adesiyun AG, Ameh N, Ozed-Williams I, Ojabo A, Umar H. Treatment outcome of hyperprolactinaemic infertility with carbagoline in sub-Saharan Africa. Pak Med Sci 2008;24:512-6.
Prathibha D, Govardhani M, Krishna PT. Prolactin levels in infertility and bromocriptine therapy in hyperprolactinaemia. J Indian Med Assoc 1994;92:397-9.
Giwa-Osagie OF, Akinla O, Coker OO. Luteal phase plasma prolactin levels and infertility: Prognosis in unexplained infertility. Niger Q J Hosp Med 1984;2:24.
Kuku SF. African endocrine infertility: A review. Afr J Med Med Sci 1995;24:111-23.
Kredentser JV, Hoskins CF, Scott JZ. Hyperprolactinemia – A significant factor in female infertility. Am J Obstet Gynecol 1981;139:264-7.
Lenton EA, Sobowale OS, Cooke ID. Prolactin concentrations in ovulatory but infertile women: Treatment with bromocriptine. Br Med J 1977;2:1179-81.
Mühlenstedt D, Bohnet HG, Hanker JP, Schneider HP. Short luteal phase and prolactin. Int J Fertil 1978;23:213-8.
Akande AA, Idowu AA, Jimoh AK. Biochemical infertility among females attending university of Ilorin teaching hospital, Nigeria. Niger J Clin Pract 2009;12:20-4.
Greer ME, Moraczewski T, Rakoff JS. Prevalence of hyperprolactinemia in anovulatory women. Obstet Gynecol 1980;56:65-9.
Hattori N, Ishihara T, Ikekubo K, Moridera K, Hino M, Kurahachi H, et al.
Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia. J Clin Endocrinol Metab 1992;75:1226-9.
Hattori N, Inagaki C. Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: Bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab 1997;82:3107-10.
Lenton EA, Brook LM, Sobowale O, Cooke ID. Prolactin concentrations in normal menstrual cycles and conception cycles. Clin Endocrinol (Oxf) 1979;10:383-91.
Jeffcoate SL, Bacon RR, Beastall GH, Diver MJ, Franks S, Seth J, et al.
Assays for prolactin: Guidelines for the provision of a clinical biochemistry service. Ann Clin Biochem 1986;23:638-51.
Josimovich JB, Lavenhar MA, Devanesan MM, Sesta HJ, Wilchins SA, Smith AC, et al.
Heterogeneous distribution of serum prolactin values in apparently healthy young women, and the effects of oral contraceptive medication. Fertil Steril 1987;47:785-91.
Eftekhari N, Mirzaei F, Karimi M. The prevalence of hyperprolactinemia and galactorrhea in patients with abnormal uterine bleeding. Gynecol Endocrinol 2008;24:289-91.
Giwa-Osagie OF, Akinla OA, Coker OO, Sanyaolu AO. Prevalence of hyperprolactinaemia and galactorrhoea in secondary amenorrhoea. Trop Geogr Med 1983;35:163-5.
Kleinberg DL, Noel GL, Frantz AG. Galactorrhea: A study of 235 cases, including 48 with pituitary tumors. N
Engl J Med 1977;296:589-600.
Johnston DG, Haigh J, Prescott RW, Heaton A, Kendall-Taylor P, Baylis P, et al.
Prolactin secretion and biological activity in females with galactorrhoea and normal circulating prolactin concentrations at rest. Clin Endocrinol (Oxf) 1985;22:661-78.
Soong YK, Ferguson KM, McGarrick G, Jeffcoate SL. Size heterogeneity of immunoreactive prolactin in hyperprolactinaemic serum. Clin Endocrinol (Oxf) 1982;16:259-65.
Olukoga AO, Kane JW. Macroprolactinaemia: Validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition. Clin Endocrinol (Oxf) 1999;51:119-26.
[Table 1], [Table 2], [Table 3]