Macroprolactinemia in hyperprolactinemic infertile women Krithika ThirunavakkarasuPinaki DuttaSubbiah SridharLakhbir Dhaliwal • G. R. V. PrashadShalini GainderNaresh SachdevaAnil Bhansali

Abstract Hyperprolactinemia occurs in 15–20 % ofwomen withmenstrual disturbances and 30–40 % ofinfertilewomen and it can adversely affect the fertility. High molec-ular weight prolactin (macroprolactin) has long been knownin hyperprolactinemic fertile women. However, the preva-lence of macroprolactinemia in hyperprolactinemic infertilewomen is not known. This cross-sectional study was carriedout during the period of June 2010 and June 2011 at a singletertiary care centre. All women who attended the infertilityclinic during this period were screened for hyperprolactine-mia and only women with hyperprolactinemia and infertilitywere further studied for the presence of macroprolactin bypolyethylene glycol precipitation assay. We compared theclinical, hormonal profile and fertility outcome of infertilewomenwithtruehyperprolactinemiaandmacroprolacinemiausing appropriate statistical tests. Of 1,163 infertile women,183 (15.7 %) had hyperprolactinemia [134 (73 %) had pri-mary infertility and 49 (27 %) had secondary infertility]. Outof these 183 women with hyperprolactinemia, one hadmicroadenoma, 161 had true idiopathic hyperprolactinemiaand 21 (11.5 %) women had macroprolactinemia. The prev-alenceofoligomenorrheaand galactorrheaweresignificantlyhigher in patients with true hyperprolactinemia than mac-roprolactinemia (46 vs. 14 %, p\0.008 and 30 vs. 5 %,p = 0.01respectively).Twenty-twopatients(13.5 %)oftruehyperprolactinemia and two (9 %) in macroprolactinemiabecame pregnant during the study period. Prolactin mea-surement should be a part of routine evaluation of couplesreferred to infertility clinics. Macroprolactin screening ismandatory when clinical features and serum PRL assayresults are conflicting. Patients with macroprolactinemiashould be investigated for causes of infertility other thanhyperprolactinemia.Keywords Hyperprolactinemia Macroprolactin Infertility GalactorrheaIntroductionHyperprolactinemia is associated with suppression ofhypothalamic–pituitary–gonadal axis through the inhibitionof the pulsatile secretion of gonadotropin releasing hor-mone (GnRH) [1]. It is one of the most common endocrinedisorders causing female infertility [2] and occurs in30–40 % of infertile women [3].Human PRL (PRL) circulates in three different forms inthe blood. Monomeric PRL (23.5 kDa—free form), whichaccounts for 85 % of the PRL, dimeric PRL (50 kDa)contributes 5–10 % and in the remaining higher molecularweight ([100 kDa) form [4, 5] contributes a small andvariable amount. The high molecular weight form (big–bigPRL) consists of an antigen antibody complex of mono-meric PRL and immunoglobulin (IgG) [6]. When the pre-dominant form of circulating PRL is [100 kDa, thecondition is termed as macroprolactinemia [7].The above three forms of PRL are indistinguishable byroutine assays and the excessive requirement of PRLdetermination led to an important laboratory pitfall [8]. The