Clinical profile and early therapeutic response to cabergoline of patients with hyperprolactinemia in a cameroonian population

Clinical profile and early therapeutic response to cabergoline of patients with hyperprolactinemia in a Cameroonian population

Martine Claude Etoa Etoga^1,2,&, Eugène Sobngwi^2,3, Pelagie Ngoune³, Emmanuella Doh³, Francine Mendane Mekobe⁴, Noel Mbango-Ekouta¹, Mesmin Dehayem², Pascal Foumane⁵, Jean Claude Mbanya^2,3

¹Department of Clinical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon, ²National Obesity Centre, Diabetes and Metabolic Diseases Unit, Yaounde Central Hospital, Yaounde, Cameroon, ³Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaounde, Cameroon, ⁴Internal Medicine Unit, Centre Hospitalier d´Essos, Yaounde, Cameroon, ⁵Department of Obstetrics and Gynecology, Faculty of Medicine and Biomedical Sciences, University of Yaounde 1, Yaounde, Cameroon

^&Corresponding author
Martine Claude Etoa Etoga, Department of Clinical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon

Introduction    

Hyperprolactinemia is one of the most frequent disorders of the pituitary gland. It is responsible for 20 to 25% of consultations of secondary amenorrhea [1] and 17% for female infertility [2], and can be caused by physiological, pharmacological or pathologic factors. Clinical presentations of hyperprolactinemia vary with study populations and depends on the etiology hence its profiling in different populations is necessary [3]. There is paucity of data concerning sub Saharan Africa (SSA). The clinical picture in this context may reflect both difficult access to care and possible ethnic/geographic specificities. The impact on the growing public health problem of infertility in Africa is unknown. Dopamine agonists are the gold standard treatment of hyperprolactinemia, although associated with various adverse effects. Cabergoline is generally preferred due to better compliance, limited side effects and good therapeutic response [4, 5]. Bromocriptine widely and satisfactorily used in a context of limited availability of cabergoline [6]. Whether the more expensive cabergoline would be effective and potentially cost saving has not been reported. We sought to describe clinical manifestations of hyperprolactinemia and response to cabergoline in a SSA setting, as improving on the diagnosis and management for hyperprolactinemia is likely to improve infertility care in this context.

Methods     

We conducted a cross-sectional study over a period of 2 years. We describe the profile of all patients with a diagnosis of hyperprolactinaemia at the Endocrinology Department of Yaoundé Central Hospital, Yaoundé. Patients with physiological hyperprolactinemia including pregnant and lactating women were not considered. Baseline work up included clinical data collection using a pre-designed questionnaire, the assay of prolactinemia by electro-chemiluminescence, ultra-sensitive thyroid-stimulating hormone (TSH), blood urea nitrogen, serum creatinine and liver function panel. Hypothalamo-pituitary MRI or CT scan was performed in all participants. All patients were routinely started on cabergoline at 0.5mg/week or at 1mg/week in case of macroprolactinoma or desire to become pregnant. Patients were monitored on a monthly basis until 5 months after initiation of the treatment then every 3-months, to assess compliance and drug tolerance using a literature-derived checklist of possible adverse symptoms or physical signs. All participants gave their informed written consent.

Results     

Participants included 24 females and 1 male aged 24 to 58 years with a mean of 37.1±8.9 years. Clinical features at presentation included mainly infertility (20/25), galactorrhea (18/25), menstrual disturbances (16/24), visual defects (4/25), and erectile dysfunction in the only male patient. The most probable causes of hyperprolactinaemia were microadenoma in 13/25, macroprolactinoma in 4/25, non-secreting macroadenoma in 4/25. No cause was identified in 4/25 cases suggesting missed microadenoma or idiopathic hyperprolactinaemia. All patients were treated with cabergoline and one non-secreting macroadenoma with visual signs required additional surgical treatment. The duration of follow up was 8-16 months. After three months of treatment, 8 of 10 patients with amenorrhea had menses, 12/18 had no more galactorrhea. Prolactin levels normalized in 16/25. Fertility was restored with confirmed pregnancy in 7/17 by the 16th month of follow up. Serum prolactin levels decreased significantly at month 2-3 (p = 0.025). Table 1 shows temporal changes in clinical symptoms and signs under treatment. Concerning adverse effects, 5/25 patients had transient dizziness, and 4 complained of headache that subsided spontaneously after two weeks of treatment without dose change. The other reported symptoms included digestive tract disorder (4/25), asthenia (3/25), oedema (1/25), and alopecia (1/25).

Discussion     

In this case series in a SSA population with confirmed pathological hyperprolactinaemia and most of patients referred by gynaecologists, there was a clear female predominance with infertility and galactorrhea being the most frequent presenting complains. According to WHO, one in every four couple in developing countries have been found to be affected by infertility [7]. A study carried out in 2012 stated that the prevalence of infertility was highest in South Asia, Sub-Saharan Africa, North Africa/Middle East, Central/Eastern Europe and Central Asia [8]. In SSA, infertility is becoming a major public health problem with strong cultural and psychosocial implications. Infertility is multifactorial with the most frequent contributor to female infertility being tubopelvic diseases [5]. The role played by hyperprolactinemia remains unknown and there is paucity of data in sub Saharan populations. Dopamine agonists are the gold standard approach for the treatment of hyperprolactinemia with good therapeutic response in general. Cabergoline and Bromocriptine are the two major ones [9]. In SSA context; most studies reported results only with Bromocriptine for availability and access reasons. In studies comparing cabergoline and bromocriptine, side effects were less frequent and severe with cabergoline [5]. In our cohort we used solely cabergoline with one case requiring an additional surgical treatment. This treatment was associated with an excellent therapeutic response as from 2 to 3 months of use despite a few minor and transient side effects most of which subsided in about 12 weeks. The promising results on fertility within a very short term of 41% compared to 28% within an average of 26 months in a study in Thailand that used mostly bromocriptine [10], suggest a more prominent role of hyperprolactinaemia in infertility in our cohort, or a better response to cabergoline or both.

Conclusion     

Our study suggests that serum prolactin levels should be measured in all patients consulting for infertility or for menstrual cycle disorders, and that cabergoline yields an excellent therapeutic response in a short period of time and may thus be cost saving in sub Saharan context despite its unit price.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Martine Claude Etoa Etoga conducted the study and wrote the manuscript; Eugène Sobngwi designed the study; Pelagie Ngoune has conducted the study; Emmanuella Doh, Francine Mendane Mekobe, Eliane Ngassam, Mesmin Dehayem, Pascal Foumane and Jean Claude Mbanya read the manuscript; Jean Claude Mbanya supervised all the work. All authors have read and agreed to the final version of this manuscript.

Acknowledgments     

We gratefully acknowledge all the patients who have accepted to take part in this study.

Table     

Table 1: temporal changes in clinical characteristics under cabergoline treatment

References     

1. Brue T, Delemer B. Diagnosis and management of hyperprolactinemia: expert consensus-French Society of Endocrinology. Ann Endocrinol (Paris). 2007 Feb;68(1):58-64. PubMed | Google Scholar


2. P G Crosignani. Management of hyperprolactinemia in infertility. J Reprod Med. 1999 Dec;44(12 Suppl):1116-20. PubMed | Google Scholar


3. Colao A, Sarno AD, Cappabianca P, Briganti F, Pivonello R, Somma CD et al. Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol. 2003 Mar;148(3):325-31. PubMed | Google Scholar


4. Colao A, Savastano S. Medical treatment of prolactinomas. Nat Rev Endocrinol. 2011 May;7(5):267-78. PubMed | Google Scholar


5. Wang AT, Mullan RJ, Lane MA, Hazem A, Prasad C, Gathaiya NW et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012 Jul 24;1:33. PubMed | Google Scholar


6. Molitch ME, Elton RL, Blackwell RE, Caldwell B, Chang RJ, Jaffe R et al. Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study. J Clin Endocrinol Metab. 1985 Apr;60(4):698-705. PubMed | Google Scholar


7. WHO. Global prevalence of infertility, infecundity and childlessness. Accessed on 23^rd Dec 2016.


8. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLoS Med. 2012;9(12):e1001356. PubMed | Google Scholar


9. 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 Aug; 65(2):265-73. PubMed | Google Scholar


10. Saejong R, Dangrat C, Techatrisak K, Angsuwatthana S, Rattanachaiyanont M, Tanmahasamut P. Hyperprolactinemia: a 12-year retrospective study at gynecologic endocrinology unit, Siriraj Hospital. J Med Assoc Thai. 2013 Oct;96(10):1247-56. PubMed | Google Scholar