Abstract
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Case 1 was a 32-year-old woman who attended for secondary infertility. Her medical history was significant for polycystic ovary syndrome and hypoplastic tubular breasts supplemented by implants at 17 years of age through an axillary approach. She achieved pregnancy while on metformin and reported lack of breast growth and engorgement, impaired milk secretion, and inability to breastfeed her first child. On examination, glandular breast tissue and implants were palpated bilaterally. Her prolactin level was 1.7 ng/mL (normal, 3–30 ng/mL) (repeat level, 2.9 ng/mL), with a normal thyrotropin level. She ovulated on clomiphene and became pregnant on a subsequent cycle while on metformin only. A second-trimester prolactin level was 21.8 ng/mL, with a third-trimester prolactin level of 119.6 ng/mL. After her second delivery there was some colostrum, but she was unable to lactate.
Case 2 was a 24-year-old woman without significant medical history who was evaluated for amenorrhea. Menarche was followed by infrequent menses. Examination revealed normal breasts and mild hirsutism. Laboratory tests were consistent with polycystic ovary syndrome. Her prolactin was undetectable, and on repeat testing levels were <0.1 ng/mL and 1 ng/mL, with a mildly elevated thyrotropin level and negative thyroid antibodies. Further workup showed normal pituitary function. She was unsuccessful in achieving pregnancy despite follicular development with letrozole. In vitro fertilization resulted in pregnancy. The prolactin level was 3.6 ng/mL in the first trimester, 8.7 ng/mL in the second trimester, and 9.7 ng/mL in the third trimester. She produced some colostrum but was unable to lactate.
Isolated prolactin deficiency is rare and apparent clinically as lack of puerperal lactogenesis. The diagnosis is established with a low prolactin level and failure of the levels to increase after administration of thyrotropin-releasing hormone or antidopaminergic medications. 3
Seven cases of isolated prolactin deficiency have previously been reported, 3 and only one subject had abnormal breast development. 2 In both our patients the prepregnancy prolactin levels were low. Despite a low-normal prolactin response to pregnancy, Case 1 failed to lactate after two pregnancies. Case 2 had a minimal prolactin response to pregnancy.
The growth and differentiation of the mammary gland are under control of various growth factors and hormones.1,4 Studies of mammary gland morphogenesis in murine models show that terminal bud formation during puberty is under the control of various factors, including estrogen, epidermal growth factor, insulin-like growth factor-2, and transforming growth factor-β, but not prolactin or its receptor.1,5 However, these studies suggest a role for prolactin in ductal side branching and alveolar bud formation. This may possibly explain the inability to lactate in Case 1; despite a prolactin over 100 ng/mL, she was unable to lactate after two deliveries, suggesting that adequate breast development before pregnancy may also be a prerequisite for lactation. Although she had implants, these were through an axillary approach, which is thought not to affect milk supply.