J Mammary Gland Biol Neoplasia
DOI 10.1007/s10911-015-9330-7
Unsolved Mysteries of the Human Mammary Gland: Defining
and Redefining the Critical Questions from the Lactation
Consultant’s Perspective
Lisa Ann Marasco 1,2
Received: 16 March 2015 / Accepted: 8 June 2015
# Springer Science+Business Media New York 2015
Abstract Despite advances in knowledge about human lac-
tation, clinicians face many problems when advising mothers
who are experiencing breastfeeding difficulties that do not
respond to normal management strategies. Primary insuffi-
cient milk production is now being acknowledged, but inci-
dence rates have not been well studied. Many women have
known histories of infertility, polycystic ovary syndrome, obe-
sity, hypertension, insulin resistance, thyroid dysfunction,
hyperandrogenism or other hormonal imbalances, while
others have no obvious risk factors. Some present with obvi-
ously abnormal breasts that are pubescent, tuberous/tubular or
asymmetric in shape, raising the question of insufficient mam-
mary gland tissue. Other women have breasts that appear
within normal limits yet do not lactate normally. Endocrine
disruptors may underlie some of these cases but their impact
on human milk production has not been well explored. Simi-
larly, any problem with prolactin such as a deficiency in serum
prolactin or receptor number, receptor resistance, or poor bio-
availability or bioactivity could underlie some cases of insuf-
ficient lactation, yet these possibilities are rarely investigated.
A weak or suppressed milk ejection reflex, often assumed to
be psychosomatic, could be related to thyroid dysfunction or
caused by downstream post-receptor pathway problems. In
* Lisa Ann Marasco
LisaIBCLC@Marasco.US
1
Expressly Yours Lactation Service, Santa Maria, CA, USA
2
Santa Barbara County Public Health Department/ Nutrition
Services/Breastfeeding Program, Santa Maria, CA, USA
the absence of sufficient data regarding these situations, des-
perate mothers may turn to non-evidence-based remedies,
sometimes at considerable cost and unknown risk. Research
targeted to these clinical dilemmas is critical in order to devel-
op evidence-based strategies and increase breastfeeding dura-
tion and success rates.
Keywords Mammary hypoplasia . Lactation failure .
Hyperlactation . Macroprolactin . Connexin43 . Serotonin .
Galactogogues
Introduction
BSome women just can’t breastfeed^ is what some mothers
hear as they seek help from their health care provider while
experiencing difficulty in making enough milk. In what other
field of study would this be an acceptable response? Certainly
not the dairy industry, which cannot afford to invest in cows
that Bjust can’t make milk.^ Any mammalian species that fails
at lactation would soon become extinct.
On-going research continues to reaffirm the critical impor-
tance of species-specific milk for neonates, including human
babies. In light of now well-established science supporting
breastfeeding, campaigns have been waged to encourage all
mothers everywhere to breastfeed, and the messages have
been heard. In 1985, lactation consulting became an
internationally-accredited profession following the establish-
ment of a certifying and accrediting agency, the IBLCE, and
The Journal of Human Lactation1 was born. In 1991, the
World Health Organization-UNICEF Baby-Friendly Hospital
1
http://jhl.sagepub.com

Initiative (BFHI)2 spurred a revolution designed to eliminate
hospital-related obstacles to the initiation and continuance of
breastfeeding [1]. Three years later, the internationally-based
Academy of Breastfeeding Medicine3 was established. Its
contributions via its academic journal, Breastfeeding
Medicine, and ongoing, continually updated evidence-based
Clinical Protocols,4 have led to expansion of the unofficial
specialty of self-identified Breastfeeding Medicine Physi-
cians. These advances, along with government and non-
governmental organization support in various countries, con-
tinue to add to breastfeeding support efforts.
At the same time, while rates for the initiation of
breastfeeding have risen, breastfeeding duration rates have
not increased proportionally as women who intended to
breastfeed longer instead find themselves weaning premature-
ly, with Binsufficient milk^ frequently cited among the top
reasons by lactation consultants world-wide as well as in pub-
lished research [2–5]. Beyond the barrier of misperceived in-
sufficient milk production and subsequent detrimental man-
agement choices lies another challenge that is only more re-
cently being brought into the light: true, real or primary insuf-
ficient milk production [6–8]. This label, which lacks formal
diagnostic criteria, is applied by lactation consultants and/or
mothers when normal appropriate breastfeeding management
[9, 10] fails to yield sufficient milk to support the baby’s
developmental needs. While many organic causes are under-
stood, if not well-documented, there are still a troubling num-
ber of clinical cases that exhibit red flags, such as a history of
hormonal problems, but do not fit into known Bboxes^ for low
milk production etiologies. The end-result is care strategies
based on limited knowledge that are more proverbial shots-
in-the-dark than validated protocols. Mothers in turn feel
overwhelmed by the lack of solid answers, leading many to
simply give up breastfeeding efforts altogether [11].
A recent article highlighted a number of critical lactation
questions that researchers in the field of human lactation iden-
tified as unresolved and in need of further pursuit [12]. In turn,
the current article describes specific unresolved clinical prob-
lems faced by lactation consultants and the need for research
support to find answers for individual mothers.
Major Issues Requiring Attention
Documenting True Insufficient Milk Production
First and foremost, it is difficult to fund research into a prob-
lem that has not been well-documented. What exactly is the
current rate of real lactation failure in humans? This question
2
http://www.who.int/nutrition/topics/bfhi/en
3
http://www.bfmed.org
4
http://www.bfmed.org/Resources/Protocols.aspx
J Mammary Gland Biol Neoplasia
was pondered in 1938 by British physician J.C. Spence, who
speculated: BConcerning the normal mechanism of lactation
there remains one other question. What percentage of women
are incapable of breast-feeding because of physical abnor-
malities? Less than one cow in a thousand fails to
lactate….There remain a few, less than five per cent, in whom
it is physically impossible to establish lactation…^ [13].
Twenty years later in an observational study of almost 900
women, Deem and McGeorge estimated that four to five per-
cent of the mothers were bottle-feeding due to primary failure
of lactation [14]. More recently, a small-scale 1990 U.S. study
again posed this question, wherein the authors found an over-
all rate of 15 % lactation insufficiency [15]. In that survey it
was noted that previous breast surgery, minimal prenatal
breast enlargement and minimal postpartum breast engorge-
ment were risk factors for insufficient milk production as de-
fined by infants failing to gain appropriate weight. Co-author
Dr. Marianne Neifert later wrote that the actual rate was likely
around 5 % [16], and when interviewed in 2013 by the Chica-
go Tribune, she reiterated that the true rate was likely in the
range of 1–5 %. She noted that there still was no further re-
search on this question but that the number of afflicted Western
women in particular seemed significant and their rate was like-
ly closer to 4 % [17]. If just 1 % of mothers in the U.S. were
affected, 39,528 mothers would have suffered from primary
insufficient milk production in 2012,5 a significant number
indeed. As suggested by Dr. Neifert, the actual rate(s) of pri-
mary lactation insufficiency may vary internationally. For this
reason, the answer might best be sought in separate epidemio-
logical studies. If there are large variances, differences between
the populations may shed light on relevant modifying factors.
In the years succeeding the 1990 study, the advent of the
Internet allowed previously isolated lactation professionals to
share difficult clinical cases through venues such as Lactnet,
an international listserv for consultants established in 1995.
With this access came increasing awareness of primary lacta-
tion problems and an improved ability to explore causes and
possible solutions with more experienced colleagues. Formal
studies of these topics are lacking, however, and so concrete
help for mothers continues to lag. The remaining sections
below discuss different scenarios encountered by clinicians,
and what is known or theorized about their connection to
lactation problems.
Infertility
In the U.S., as many as 15 % of women experience infertility
[18–20]. When they finally overcome their personal health/
reproductive issues and deliver their baby, the last struggle
they expect to face is breastfeeding. It is commonly assumed
5
CDC reports that 3,952,841 babies were born in the U.S. in
2012 (http://www.cdc.gov/nchs/births.htm)
J Mammary Gland Biol Neoplasia

that if a woman can get pregnant and carry her baby to term, [32], and high testosterone during the immediate postpartum
then successful lactation should follow- Bif she can gestate, period due to a gestational ovarian theca-lutein cyst has been
she can lactate.^ This belief is now being questioned by documented to suppress lactogenesis II [33]. A Norwegian
mothers who are starting to clamor for help, both for the cur- study following a group of PCOS mothers matched with con-
rent nursling as well as proactively for future babies. We need trols found a Bweak relationship^ between mid-pregnancy
to start by studying the incidence of primary lactation prob- levels of dehydroepiandrosterone-sulphate (DHEAS) and
lems among infertility patients versus normal control mothers, breastfeeding rates early postpartum, leading to the conclusion
and then start looking at the particulars of each situation for that PCOS may negatively affect early lactation [34]. A
clues on what may be interfering with lactation. follow-up study by Carlsen et al. checked mid-pregnancy
levels of androgens in women likely to be hyperandrogenic,
matched them with controls, then observed the course of
Polycystic Ovary Syndrome: Obesity, Hyperandrogenism,
breastfeeding in both groups [35]. In the at-risk group,
and Insulin Resistance
breastfeeding was negatively correlated with DHEA levels,
while unexpectedly it was found that the free testosterone
Polycystic Ovary Syndrome (PCOS) is a leading cause of
index correlated negatively with breastfeeding in the control
infertility in women. The 2003 Rotterdam Consensus spec-
group. The authors concluded that mid-pregnancy androgen
ifies the diagnosis when at least two of three of the following
levels negatively affect breastfeeding, but were unable to iso-
are present: oligo- or anovulation; clinical6 or biochemical
late a pattern among the specific androgens.
evidence of hyperandrogenism7; polycystic ovaries [21]. The
It is important to keep in mind that not all hyperandrogenic
Androgen Excess and PCOS Society and the National Insti-
women have the masculine body shapes that Routh observed.
tutes of Health have similar criteria, requiring clinical or bio-
In addition, clinical symptoms such as hirsutism may not be
chemical evidence of hyperandrogenism as well as evidence
obvious as many women are diligent to hide such evidence
of menstrual dysfunction, and all three require exclusion of
with waxing, shaving or hair removal, while some women
other androgen excess or related disorders [22]. The classical-
exhibit no outward manifestations at all.
ly recognized presentation includes obesity, although approx-
Another major risk factor for lactation failure in mothers
imately 30–50 % of women with PCOS are not obese [23, 24].
with PCOS is insulin resistance, especially when it progresses
Failure to ovulate regularly results in low progesterone, an
to gestational diabetes or Type 2 diabetes [36, 37]. Ground-
important stimulator of mammary tissue, and insulin resis-
breaking research with gene sequencing is taking us from
tance is also common. Additional frequent co-morbidities in-
Bassociation^ with decreased milk synthesis to the mechanism
clude hypothyroidism [25, 26], metabolic syndrome, hyper-
of this effect via the protein tyrosine phosphatase, receptor
tension, glucose intolerance and diabetes [22]. Current re-
type F (PTPRF), directly linking insulin resistance with insuf-
search now suggests that poor metabolic health can have a
ficient milk supply for the first time [38, 39]. By extrapolation,
negative effect on lactation [27–29], a troublesome portent
this finding supports strategies such as metformin therapy to
for mothers with PCOS.
address impaired milk synthesis via treatment of the underly-
Among the common endocrinopathies of PCOS,
ing pathogenesis.
hyperandrogenism, an excess of one or more male hormones,
Two studies so far have examined PCOS, metformin and
stands out as a risk factor for problems associated with milk
milk production. Thatcher et al. [40] performed a single-center
production. As far back as 1879, British physician Charles
retrospective case study of the effects of metformin on preg-
Routh described women who were Brather masculine in form
nancy outcome wherein 188 mothers were prescribed 500–
and character^ in his third category of deficient lactation
2000 mg of metformin prior to conception in accordance with
types [30]. Androgens have an inhibitory effect on breast de-
individual maternal hormonal profiles; most discontinued the
velopment and play a limiting role in breast growth by oppos-
drug by the end of the first trimester. For those whom
ing the stimulatory effects of estrogen; an imbalance favoring
breastfeeding information was available, 22 % of the women
androgens can result in suppression of mammary develop-
who tried to breastfeed did not succeed, with only 4 citing
ment [31] along with other symptoms such as hirsutism (ex-
problems with milk. The author concluded that women with
cess body hair), alopecia (male-pattern balding) and adult acne.
PCOS did not differ from unaffected mothers in their ability to
Exogenous testosterone was once used to suppress lactation
breastfeed, but also did not account for the fact that all the
6
Clinical symptoms may include excess body hair (hirsut- mothers were under a treatment that could have influenced
ism), adult acne, and/or male-pattern balding (alopecia) breastfeeding outcome. Other reasons listed and not explored
7
Hyperandrogenism is the excess of one or more male hor- were multiple pregnancies and premature delivery.
mones and includes testosterone, dehydrotestosterone (DHT), In a prospective case control study, Vanky et al. [34] select-
dehydroepiandrosterone (DHEA), dehydroepiandrosterone ed 40 pregnant women diagnosed with PCOS using the Rot-
sulfate (DHEAS) and androstenedione. terdam Consensus 2003 criteria. All of the women were

randomized to 750 mg metformin BID and then matched with
controls. No relationship was found between metformin and
lactation outcome, but insulin resistance was not recorded or
tracked, raising the question of whether the women were ap-
propriate candidates for therapy.
Both of these studies have significant draw-backs, but are
currently the only reports available to inform physicians on
the use of metformin to assist lactation. As a result, very few
mothers find help from their health care providers despite the
fact that, anecdotally, a number of women have reported im-
provements in milk output with metformin treatment. For this
reason many mothers turn to botanical galactogogues such as
fenugreek (Trigonella foenum graecum) and goat’s rue
(Galega officinalis) [41] as alternate strategies, with some
reporting good results. Both of these herbs, interestingly, have
anti-diabetic as well as lactogenic properties.
Some mothers with PCOS clearly have abnormal breast
development. Irving Stein and Michael Leventhal, who in
1935 originally identified the syndrome now known as PCOS,
described unusual breast development among some of their
patients: Bin cases of prolonged amenorrhea…small, firm and
pale^ [42]; Bretarded breast development [43]; Bin many in-
stances, hypoplasia of the breasts^ [44] (Fig. 1). Not until
1972 did researchers look specifically at the breasts of women
with PCOS and observe five distinct types of abnormal
breasts, commenting that some had Bevidence of marked de-
creases in the glandular parenchyma… even where large
breasts with much fatty tissue simulate hypertrophy.^ [45]
(Fig. 5a and b) The findings of the deceptive hypertrophic
breasts were echoed in 2002 by Cruz et al., who found signif-
icantly less glandular tissue than normal among 25 women
presenting for surgery due to macromastia [46]. Despite these
alarming observations and their implications for lactation, the
possibility that PCOS endocrinopathy could negatively affect
lactation was not broached until a case study of three mothers
was published in 2000 [47].
Obesity is a significant risk factor for women both with and
without PCOS [48]. Obese women are more likely to develop
insulin resistance and diabetes, which can stimulate further
androgen production [49]. They are less likely to experience
normal breast changes during pregnancy, which may lead to
reduced lactation capacity postpartum [28]. These women al-
so have higher rates of hypertension as well as lower prolactin
(PRL) responses to suckling [50], the latter of which may
interfere with the maintenance of sufficient milk production.
Despite compelling research and theories, solutions for
PCOS mothers with primary lactation problems are sorely
lacking. Complicating progress on this topic is the heteroge-
neous nature of the syndrome. When symptoms and presen-
tations vary, it is more difficult to pinpoint causes of lactation
problems. One interesting approach that PCOS researchers are
using to assess risk is categorizing women by combinations of
the Rotterdam consensus phenotypes to see if there are some
J Mammary Gland Biol Neoplasia
combinations that result in poorer health outcomes than others
[51]. Palomba et al. explored the risk of PCOS phenotype
combinations on pregnancy and neonatal health (ie, miscar-
riage, pregnancy hypertension, gestational diabetes mellitus,
premature delivery, small or large fetal size, etc.), and discov-
ered that the risk of adverse outcome was highest when ovar-
ian dysfunction or biochemical hyperandrogenism were pres-
ent, and lowest with clinical hyperandrogenism and polycystic
ovaries [52]. If one additional outcome had been added to the
list of adverse events—primary lactation problems— we
might have learned something important that could have been
applied as a screening tool for lactation risks. A collaboration
between lactation and PCOS researchers has the potential to
illuminate this question not only for women with PCOS, but
more broadly for any woman with one or more of the pheno-
types, regardless of diagnosis.
Most physicians are reluctant to pursue testing or treat-
ments when there is no specific published evidence to suggest
or support it, even in the presence of strong hypotheses. Thus,
we need research that looks at the overall rate of lactation
insufficiency among PCOS mothers, and further studies that
delve deeper into what is not working well in the subset of
PCOS mothers who appear to have primary lactation
insufficiency.
Maternal Age
While female fertility peaks in the mid- to late twenties
[53], the rate of women bearing children at an advanced
maternal age (generally 35 years and older) has risen con-
siderably in industrialized countries, with associated in-
creases in infertility and pregnancy outcome risks [54,
55]. Routh listed advanced maternal age in one of his
three categories of causes of Bdeficient lactation^ [30].
Yet, there has been little formal exploration of the impact
of advanced maternal age on milk output even as lactation
consultants field questions from mothers wondering if
their age is the reason for their milk production struggles.
A study on breastfeeding during an overlap of pregnancy
made a peripheral finding that milk intake by infants de-
creased by 25 g for each 5-year increment of maternal age
[56]. Another study on factors for delayed onset of lacta-
tion among first-time mothers discovered a relationship
between older maternal age and delayed onset of lactation
[57]. A recent study of Japanese mothers noted that the
rate of exclusive breastfeeding in women 40 years of age
or older was significantly lower independent of other var-
iables [58] while a second study of Japanese mothers
found a Bmarginal association^ between older maternal
age and lower milk volume on day 4 [59].
For older mothers struggling to exclusively breastfeed their
infants, these observations may validate their experience but
fall short of providing an explanation or further guidance.
J Mammary Gland Biol Neoplasia
Fig. 1 PCOS Mothers with underdeveloped/abnormal breast tissue and
low milk production. a. Extremely underdeveloped breast tissue and
coarse hairs on areolae of a mother with early onset of PCOS. No
noticeable breast growth occurred during pregnancy; only a walnut
amount of glandular tissue was palpable and she produced only a few
milliliters per nursing session. b. Pubescent breasts with scant palpable
breast tissue, no visible veining, and no pregnancy breast changes. c.
34 years. old woman with PCOS and a history of 3 pregnancy losses over
10 years. No reported pregnancy breast growth or visible veining,
Affected mothers are encouraged to feed more often, express
milk after feedings for additional stimulation, and perhaps
explore galactogogues. Unfortunately, these measures do not
always compensate for the deficit. Given that mammary tissue
regresses and is gradually displaced by fat after age 35 [60], it
is possible that some women may not enter pregnancy with a
good complement of viable glandular tissue, as hypothesized
by Dewey et al. in 1986 [61]. Another possibility is that the
decline in insulin function—synthesis and/or resistance—typ-
ically seen with aging [62] may result in a more sluggish
breast response and milk synthesis. Clearly many older
mothers lactate successfully, but humans age at different rates
that are influenced by variables such as genetics, nutrition and
exercise, which may account for the lack of predictability in
impact. Further research is needed to confirm these
delivered at 36 weeks gestation. Baby was put to breast often without
measureable milk transfer. Mother pumped q2 h for 1 oz (30 mls) total
yield over 24 h. d. Small, fatty breasts with little glandular tissue as
demonstrated by palpation. e. Complete lactation failure in a PCOS
mother with clinical and biochemical hyperandrogenism; only a drop
could be expressed. Numerous coarse hairs dot the areolae. f. Gravida 2
mother with a history of unsuccessful breastfeeding. No visible veining;
nipple-areola complex is moderately herniated
observations, identify the mechanism(s) underlying the prob-
lem, and if possible develop targeted treatments to improve
milk production for affected mothers.
Mammary Hypoplasia
Only a handful of articles in the past few decades [63–66]
have addressed the problem of primary lactation problems
due to inadequate mammary gland tissue. Recently, however,
groups have sprung up on social media sites dedicated to
mothers struggling with low milk production that is suspected
to be caused by mammary hypoplasia, also referred to as in-
sufficient glandular tissue (IGT). A book has now even been
published on this phenomenon [67]. Missing from the picture
are any in-depth studies of what is happening with these
 J Mammary Gland Biol Neoplasia

Fig 5 Normal-appearing breasts

that did not lactate normally;
desperate measures to make more
milk. a. BClassic^ PCOS mother
with hyperandrogenism, large,
fatty breasts and low milk
production. PCOS symptoms
were apparent in her early teens.
b. Side view of same Bclassic^
PCOS mother. Note fatty shelf of
breast tissue that extends under
the axilla. c. Severe engorgement
and intractable milk stasis in a
woman diagnosed with
hyperthyroidism (TSH of .0006 at
18 weeks gestation) that was still
poorly controlled at delivery. d.
Long, pendulous breasts of a
mother whose milk flow was
slow, and required long pumping
sessions with extensive
compressions and Bwringing^ to
reach and maintain full
production. e. BGalactogogue
stash^ picture posted by a mother
on Facebook. e. The burden and
desperation of mothers with
insufficient milk production

under-performing breasts. In some cases, hypoplasia is clearly
evident visually, while in others the Bdiagnosis^ is made, ac-
curate or not, based on lack of breast growth during pregnancy
and postpartum, scant palpable glandular tissue (Fig. 1), wide
spacing between breasts (Figs. 1a, b, c and 2c, d), asymmetric
or abnormal shape (Fig. 3a, b, c and d), and/or lack of signif-
icant veining (Figs. 1a, b, c, d, f and 2b, d), the latter presum-
ably signifying the presence or absence of active glandular
tissue in pregnancy/lactation [7, 64, 67].
Although there is a lack of research into lactation prob-
lems due to mammary hypoplasia, plastic surgery litera-
ture certainly validates the existence of abnormal breasts.
Women with unusually small breasts (Fig. 4a), or women
with noticeable asymmetry (Fig. 3a, b, c and d), frequent-
ly seek out breast augmentation or reduction. Women with
abnormally droopy breasts, also known as ptosis (Fig. 4b,
c and d) may become breast lift (mastopexy) patients. The
occurrence of lactation problems among women with a
prior history of such breast surgeries is well known [68,
69], yet lactation literature focuses largely on the contrib-
uting factor of the surgical technique rather than any pre-
existing glandular pathology.
Tubular or tuberous breasts, sometimes also referred to as
Snoopy deformity, are well known to plastic surgeons [70].
They have previously been described as having Bnormal func-
tion but abnormal morphology^ [60], but a histological study
discovered abnormalities in the arrangement and quantity of
collagen fibers [71], suggesting that perhaps tuberous breasts
may not be so functionally normal after all. Developmentally
they are described as Ba hypoplastic breast with constricting
ring around the base of the breast, breast tissue herniation
into the areola, deficient skin envelope and inframammary
fold malposition^ [60]. A common resulting feature is a dis-
proportionately large and protrusive areola (Fig. 2a and b).
Tubular breasts can occur unilaterally or bilaterally; in the case
of asymmetric tissue, anecdotally the smaller breast is often
more tubular in shape.
The difficult question regarding hypoplasia is that many of
these breasts fail to elicit appropriate growth in response to
endogenous pregnancy hormones, and milk synthesis also re-
sponds poorly to infant demand. In mammary biology the
breast is considered to be plastic and responsive to changes
in demand. Why, then, do some women’s breasts simply not
respond in the natural fashion? What is different about them?
J Mammary Gland Biol Neoplasia

Fig. 2 Variations of tubular/

tuberous breasts in women with
insufficient milk production. a.
BSnoopy^ tuberous breast shape
with constricted base and
herniated areolae. Photo courtesy
of Joan Fisher, IBCLC. b. Bra cup
size AA, herniated areola, no
breast growth during pregnancy,
produced less than 10 mls per
feeding. c. Wide-set breasts with
continuous shelf of soft, puffy
tissue in between and golf ball-
sized glandular tissue. Milk
transfer was less than 5 ml per
feeding. Her own mother had
normal breasts and successful
lactations. d. Extremely widely
spaced breasts; her left is more
tubular than right

Aberrant maternal hormone levels, such as hyperandrogenism
during critical fetal and pubertal mammary development win-
dows may be responsible for some of these breasts [31]. An-
other seldom-discussed possible etiology is problems with
mammary hormone receptors rather than hormone levels. In
a case study of a young woman with nipples but no breast bud,
a biopsy of the mammary gland area revealed a severe defi-
ciency in both estrogen and progesterone receptors [72].
While such cases are rare, we neglect to consider that prob-
lems can occur on a continuum of severity, and so mammary
hormone receptor deficiencies have not been explored in
women with poorly performing breasts. To be fair, suspected
mammary hypoplasia is difficult to study in human mothers
because of the need to obtain tissue samples through invasive
biopsies. On the other hand, new technology utilizing epithe-
lial cells from milk fat would make this research easier to
conduct.
Obvious mammary hypoplasia seems to be less common
than the more frequent clinical presentation of ambiguous
breasts that have suspected, but not severe, appearance of
hypoplasia. Anecdotally, these breasts have more subtle
markers of abnormality, such as high inframammary folds

Fig. 3 Variations of asymmetric

breast development in women
with primary low milk
production. Many of these
women may seek correction
through plastic surgery. a.
BClassic^ asymmetrical
presentation. Photo courtesy of
Anna Swisher, IBCLC. b.
Extreme asymmetry with most
production from left breast. c.
Markedly different breast shapes
in a mother with chronic low milk
production. d. Mild asymmetry in
a gravida 3 mother at 4 months
postpartum producing 6–9 oz
(180-270 mls) per day. Menarche
did not commence until she was
placed on birth control pills at age
19; PCOS was diagnosed at age
23

Fig 4 Various types of hypoplastic breasts that often become candidates
for augmentation or breast Blift^ surgery. a. Pre-augmentation photo of a
woman at age 20 with poorly developed breast tissue and bulbous areolae.
Over three children she was finally able to produce a maximum of 16 oz
(480 mls) with the last baby. b. Overweight and bulimic during puberty,
this mother had no breast changes during pregnancy and sought help
when her baby failed to regain birth weight. A breastfeeding medicine
physician diagnosed low prolactin and hypoplastic breasts. Milk
and deficiencies in the medial portions of the breast only [64,
67].
Endocrine Disruptors: Are They Causing More Problems
than we Know?
Some cases of low milk production defy explanation, as
was the case of a registered dietitian who herself provided
breastfeeding education and counseling to pregnant and
new mothers. She had a clean health history, no insulin
resistance, and normal appearing breast tissue with report-
ed prenatal breast growth of at least one bra cup size.
However, lactogenesis II occurred so sluggishly that it
was difficult to tell when it happened. During the first
consult at 2 weeks postpartum, the baby consumed just
12 g. If the mother pumped in lieu of breastfeeding, the
yield was the same. Her health care provider agreed to
check serum PRL, and then prescribed domperidone.
The mother’s baseline PRL was 30 ng/mL, and after
3 weeks of domperidone therapy titrated to 80 mg/day,
J Mammary Gland Biol Neoplasia
production increased to 75 % of baby’s needs with domperidone,
galactogogue herbs, and post-feed pumping stimulation. c. Side view of
a mother with breast ptosis and poor milk production. Some mothers refer
to this variation as Ba tennis-ball-in-a-sock^ shape. Photo courtesy of
Linda Anderegg, IBCLC. d. Front view of same mother with
deficiencies of glandular tissue in upper and medial areas. Photo courtesy
of Linda Anderegg, IBCLC
had risen to 82 ng/mL. Her milk output, however, topped
out at just 22 mls per session. Upon further questioning,
the mother shared that her own migrant worker mother
toiled in the strawberry fields while pregnant with her,
and that she herself grew up Bacross the street^ from ag-
ricultural fields. An intriguing study of Yaqui women in
Mexico found troubling anomalies in mammary growth in
young girls growing up in a modern agricultural environ-
ment versus those from a nearby mountainous traditional
ranching environment [73]. While the breasts of the girls
appeared the same externally, upon palpation it was dis-
covered that a significant number of those who dwelled in
the farm lands had deficiencies in the volume of their
glandular tissue. No follow-up research regarding future
lactation for these girls has been published, but one sub-
sequent article predicted future lactation problems [74].
Animal research has certainly validated negative impacts
of various chemicals upon both maternal and off-spring
mammary development as well as lactation, but human
research into whether chemicals in the environment are
J Mammary Gland Biol Neoplasia
disrupting mammogenesis and milk synthesis continues to
lag [75] despite the alarm raised by one lactation research-
er as far back as 1995 [76].
Prolactin
Given that PRL is critical for mammary gland development
and milk synthesis, scant information exists regarding the re-
lationship between PRL and low milk production in human
mothers. Cox et al. did not find a direct correlation between
serum PRL levels and milk output [77], but a more recent
retrospective longitudinal study by O’Brien et al. observed a
significant positive correlation between maternal PRL levels
and milk transfer at both 5 and 7 months postpartum, as well
as a weaker correlation between PRL at 2 weeks and milk
transfer at 7 months [78]. Interestingly, an old study in cows
noted correlations between serum PRL and milk output at one
hour post-milking, suggesting that PRL response to milking
stimulation may be more significant than baseline PRL [79].
Primary PRL deficiency is considered rare, but serum PRL
levels that are inappropriately low for lactation may have other
etiologies.
Lower PRL response to suckling—which would result in
lower baseline levels– has been reported in women who had a
family (but not personal) history of alcoholism, raising ques-
tions regarding what type of epigenetic mechanism might be
at play [80]. Obese women also have been documented to
have lower PRL surges during breastfeeding than their unaf-
fected counterparts [50]. What other factors might inhibit the
normal PRL surges in nursing women?
One enigmatic case involved a primiparous mother of nor-
mal BMI with a clean health history and no problems during
pregnancy or delivery. Lactation commenced normally with
excellent management; nevertheless, at 2 weeks postpartum
the mother sought help because her baby seemed less satisfied
and she believed that her production was dropping. Pre- and
post-feeding weights on a sensitive electronic scale indicated a
moderate (less than 90 mls) amount of milk transfer to the
baby. Because this sounded like a simple case of perceived
insufficient milk, suggested therapies included breast com-
pression, frequent feeds and an herbal galactogogue in the
hopes of bolstering production and maternal confidence. Nev-
ertheless, 1 week later the diligent mother reported softer
breasts, shorter duration of active feeding at the breast, and
increased infant fussiness with a need for formula supplemen-
tation. The test feed revealed a milk transfer significantly less
than the first visit. By 1 month the mother could only express
drops and a baseline serum PRL test came back at 5 ng/mL, on
the low side even for non-pregnant, non-lactating females of
childbearing age. Clearly she had PRL to initiate lactation in
the beginning, but what happened after that?
Clinically, this author has worked with mothers whose milk
production was insufficient from the start of lactation, where
their PRL levels at 3 to 8 weeks postpartum ranged from 5 to
30 ng/mL. In some cases there were confounding factors such
as infant suck problems, but in all cases production failed to
respond to increased feedings, the addition of pumping, or the
addition of galactogogues. If a woman can induce lactation
with simple breast stimulation, why are the breasts of these
pregnancy-primed mothers unable to lactate normally or re-
spond to stimulation? One possibility that deserves further
study is a recently identified phenomenon of autoantibodies
that specifically target PRL-secreting cells [81, 82]. With the
increased revised rates for autoimmune illnesses [83], this
may eventually explain some cases of lactation failure.
The level of circulating PRL rises gradually during preg-
nancy in response to estrogenic stimulation. Successful
lactogenesis II is dependent upon sufficiently high levels of
PRL, insulin and cortisol at the time of birth [84]. There is a
tendency to assume that a mother’s PRL level has increased
normally during the pregnancy and that the problem com-
menced after birth. Might some women have been set up for
failure even before birth due to inadequate increases in PRL?
It might prove illuminating to study women with a history of
unexplained lactation problems to see if their estrogen and
PRL levels rise to appropriate ranges during pregnancy [85,
86], and then how well they respond to the stimulation of
nursing thereafter. How robust are their pregnancy breast
changes [87]? What would their PRL and milk output curves
look like?
It is easy to understand why a breast isn’t making milk when
serum PRL is low, but we also see women who appear to have
normal breast tissue and changes during pregnancy, normal
thyroid function, appropriate PRL levels for stage of lactation
[88] and no other apparent risk factors. Yet, they cannot pro-
duce enough milk to support their infant even with increased
milk removal and stimulation. This scenario begs the question
of whether a problem might exist with their PRL bioavailabil-
ity or bioactivity. Currently, PRL is measured in total and there
are no routine clinical tests that measure PRL binding as is
possible with androgens. Are there variations in bound versus
free circulating PRL? If so, is there an approximate ratio that is
associated with good milk production? Relatedly, PRL has
been identified as occurring in at least 3 forms: monomeric
(small, most common), big prolactin and big-big prolactin
(macroprolactin) [89]. Macroprolactin in particular appears to
have lower bioactivity; might some women with apparently
appropriate PRL levels actually have too much macroprolactin
and not enough monomeric PRL? Fortunately, a new study
will soon be the first to explore this question.8
Another curious issue is the role of extra-pituitary PRL. In
mice the production of autocrine PRL by mammary epithelial
8
T. Hale, personal communication. http://www.infantrisk.
com/content/presence-macroprolactinemia-mothers-
insufficient-milk-syndrome

cells is required for differentiation of the epithelium in late
pregnancy as well as for the initiation of lactation [90]. Does
this apply to humans as well? Is there ever a human scenario in
which there is inadequate autocrine PRL production, resulting
in failure of lactation in the face of normal measurable serum
PRL levels?
History of hyperprolactinemia prior to pregnancy - with its
many potential etiologies - poses an enigma for women who
do not produce sufficient milk for their babies [91]. Case stud-
ies suggest that the type of treatment, i.e., radiotherapy, sur-
gery or medication, may permanently affect PRL response and
lactation outcomes [92, 93], yet this has not been sufficiently
explored and both mothers and their doctors remain largely in
the dark regarding the impact of various treatments on lacta-
tion. Guidelines for management and prognoses of these con-
ditions among women who wish to breastfeed are desperately
needed.
Prolactin Receptors
Another possible explanation for lactation problems is the
status of PRL receptors (PRLR) within the breast. Did the
mother start lactation with a sufficient complement of normal-
ly functioning receptors? Did these receptors respond to feed-
ing stimulation and upregulate normally? Ingram et al. noted
that higher levels of circulating progesterone and PRL during
pregnancy were associated with greater milk output at 1 week.
They also noted that primiparous women had higher serum
PRL levels than did multiparous women, and hypothesized
that the latter group may have more PRLR to bind PRL,
resulting in lower measureable serum PRL [94]. In rats, PRLR
in mammary tissue declined when hormones were altered fol-
lowing ovariectomy, adrenalectomy and hypophysectomy
[95]. In another, hyperthyroid rats experienced diminishment
of long and short PRLRs in the early postpartum, leading the
authors to speculate about the potential for lactation failure
[96]. How might various hormonal imbalances in women af-
fect PRLRs and the course of lactation? Beyond the adequacy
of receptor numbers and their ability to up-regulate appropri-
ately is the question of how much the type of receptor- long,
intermediate or short—matters, and if so, whether these vary
in women with low milk production. There also is the question
of receptor affinity/resistance; one study theorized that PRL
resistance was the cause of a mother’s lactation failure [97]. In
the face of unexplained lactation failure, these issues are ripe
for exploration.
Prolactin Replacement Therapy
Currently, women with low PRL who do not respond to phys-
ical stimulation or pharmaceutical galactogogues such as
domperidone have no further therapeutic options. Iwama
et al. documented a case in which the mother had almost no
J Mammary Gland Biol Neoplasia
PRL due to destruction of pituitary lactotrophs by auto-
antibodies; the mother subsequently was enrolled in a PRL
replacement study and successfully lactated while receiving
recombinant human PRL. Once the study ended and the drug
was withdrawn, lactation ceased [81]. Further research and
development efforts have stalled due to the loss of the one
source of the drug, as well as research funding. It is ironic that
hypothyroidism is treated with replacement hormone, not
thyroid-stimulating drugs, yet PRL replacement has been
overlooked and dismissed as an unprofitable treatment for a
rare condition. If all unexplained low milk production cases
were tested and serum baseline and rise (response to feeding
stimulation) PRL levels documented, perhaps PRL deficiency
during lactation might be found to occur more often than is
currently believed, paving the way to justifying funding and
development of treatments such as PRL replacement therapy.
Thyroid Hormones
The thyroid gland influences a number of other hormones,
including some involved with mammary development and
lactation [98]. A small study of 16 mothers observed a signif-
icant positive relationship between thyroid hormones and milk
production [99]. At present, however, research into the impact
of thyroid dysfunction on human lactation is scant [100–103]
and most of what we currently know comes from animal stud-
ies [101, 104–106]. Significant hypothyroidism during preg-
nancy in rats affects mammary development, postpartum se-
rum oxytocin concentrations/milk ejection, and lipid content
of the milk [107–109] with resultant poor growth of pups.
Clinically, a number of women have reported reduced milk
production associated with hypothyroidism, and in many
cases milk yield improved with thyroid hormone replacement
treatment or adjustments. However, a glaring gap in the
identification of thyroid dysfunction is the unsettled question
of appropriate ranges for thyroid function [110, 111]. Many
reproductive endocrinologists believe that reproductive capa-
bility is optimal when thyroid function is kept in a tighter
range (TSH 0.5–2.5 mIU/l), including during pregnancy
[112], and indeed at least one study showed that the rate of
miscarriages increased when TSH was between 2.5 and
5.0 mIU/l [113]. An older study noted that lactation problems
may be an early indicator of trouble before thyroid dysfunc-
tion becomes evident [114], providing credence to the idea
that perhaps lactation may also be negatively affected in bor-
derline or subclinical thyroid dysfunction cases. In the ab-
sence of specific human research, however, most physicians
are not aware of any connections between thyroid function
and lactation and so rarely share a mother or lactation consul-
tant’s sense of urgency in wanting to rule this possible cause
out.
Induction of hyperthyroidism during pregnancy in rats
accelerated mammary development and early onset of
J Mammary Gland Biol Neoplasia
lactation, but reduced serum oxytocin release and milk ejec-
tion, thereby limiting milk transfer and pup growth, leading to
early involution [115]. This author and another clinician have
documented cases in which women had poorly controlled hy-
perthyroidism during pregnancy, followed by an early and
dramatic onset of lactogenesis II, failure of milk ejection, pain-
ful engorgement from milk stasis and then mastitis, paralleling
the rat study (Fig. 5c). The application of a breast pump and all
the usual treatment measures failed to resolve the crisis,
resulting in the abandonment of breastfeeding. These mothers
have yet to be studied formally and so there are no treatment
guidelines. While the induction of milk ejection using exoge-
nous oxytocin (ie, nasal spray) would seem a logical ap-
proach, the lack of anything formal in the literature precludes
the consideration of this type of proactive treatment.
Complicating the thyroid dysfunction and lactation picture
are apparently contradictory reports of hyperlactation with
hyperthyroidism. This author has documented a case in which
a mother’s hyperthyroidism was brought under control prior
to conception and continued to be well-controlled during the
pregnancy. After the first month postpartum, however, she
began to experience her earlier symptoms and then problem-
atic oversupply of milk developed that, when tested, paralleled
a drop in her TSH. Why did she not experience suppression of
the milk ejection reflex as happened to mothers whose hyper-
thyroidism onset during pregnancy? The high rate of milk
secretion itself is supported by the rat studies; it is the ability
to still eject milk that sets these women apart. The answer may
lie in the timing of onset and/or the degree of severity of the
hyperthyroidism, but only research can illuminate this
paradox.
In the absence of research outlining the impact of thyroid
dysfunction on lactation, many physicians are not aware of the
potential implications of postpartum thyroiditis, clinical, and
even subclinical problems for breastfeeding. As a result, sad
tales abound of mother’s requests for testing/treatment being
dismissed as unnecessary; one mother was even told by a
reproductive endocrinologist that the thyroid has nothing to
do with lactation! These cases need to be documented and
hormone levels studied in order to understand what is happen-
ing so that we can generate strategies for timely treatment.
Milk Ejection Problems
Milk removal is central to the continuation of lactation; when
milk ejection does not function well, lactation does not sustain
well [116]. Inadequate milk removal leads to down-regulation
of milk synthesis. In bovines, a higher percentage of residual
milk correlates with a lower persistency of lactation [117],
reinforcing the importance of a robust milk ejection reflex.
The ability of stress to inhibit the milk ejection reflex has
been studied and is well recognized [118, 119]. Beyond stress
and thyroid dysfunction, other cases of impaired milk ejection
do not seem to line up with any recognizable pathology. A
mother of two with long pendulous breasts (Fig. 5d) was un-
able to provide enough milk for her first child, who also had
low muscle tone problems. When her next child was born, she
was diligent to pump after all feedings in order to establish
better lactation her second time around. This baby also had
low muscle tone, but with aggressive pumping and the use of
galactogogues, the mother worked her production up to 36 oz
(1080 mls) per day. One key issue that emerged was a very
sluggish milk ejection reflex. Her ability to maintain her milk
volume required 30 min double-pumping sessions with breast
compression and Bwringing out^ of the tissue to extract milk.
The role of the baby’s suck was explored through an unortho-
dox experiment in which the mother and a close friend with
normal lactation switched babies to see how each child fared
with the other’s milk ejection. It was noted that the friend’s
baby fed much slower from the client mother than from her
own mother, and that the client’s baby fed better from her
friend’s breast, though they both had breasts full of milk at
the time.
In clinical practice it is not uncommon to see long pendu-
lous breasts drain slowly, more so when milk production is
low and there is less volume to propel milk down lengthy
ducts to the nipple. However, this did not seem an adequate
explanation given the mother’s generous milk production. An
exploration of the literature for other causes of milk ejection
problems revealed intriguing information regarding problems
with connexin43, a gap junction protein expressed in
myoepithelial cells and in the stroma, and impaired mammary
development and milk ejection [120–123]. High glucose
levels are known to alter Connexin43 expression in the rat,
contributing to diabetic retinopathy [124]. Given the current
obesity and diabetes epidemic in western countries such as the
U.S., could the same mechanism play a role in milk ejection
problems for some women?
Serotonin
Perinatal and postpartum depression afflict many women in
western societies [125]. Selective Serotonin Reuptake Inhibi-
tor (SSRI) medications are widely used to treat depression in
this population. Most lactation research is largely focused on
the passage of these drugs into breastmilk and safety of the
infant. However, bovine and rat research demonstrates that
serotonin plays a role in mammary gland regulation, with
disruption of normal serotonin levels leading to accelerated
decreases in milk synthesis and glandular involution
[126–128]. Hernandez et al. added the discovery that rat dams
fed high-fat diets have abnormal mammary gland morphology
with few, small alveoli and delayed lactogenesis II [129] as-
sociated with increased serotonin production in the gland,
leading to the theory that this may be an underlying mecha-
nism for delayed lactation in some obese women. Marshall

and colleagues conducted a parallel study of mice and human
mothers to examine the effects of an SSRI medication
(fluoxetine) during pregnancy on mammary gland tissue and
lactation. Almost all of the SSRI mothers experienced signif-
icant delays in secretory activation, leading the authors to call
for more research with larger numbers of women and different
types of SSRI medications while urging extra support be ex-
tended to mothers taking SSRIs. Given the high number of
women expressing concern about their milk production and
the widespread use of SSRIs in pregnant and lactating women,
it is critical that the research continue in order to identify the
medications that will be least harmful to milk production as
well as the infant.
Hypertension
Hypertensive disorders, including chronic, pregnancy-
induced and pre-eclampsia, affect 5–10 % of all pregnancies
[130]. While the negative impact on lactation is recognized [6,
9, 131, 132], formal research into the possible mechanisms of
interference in human mothers has lagged. One study compar-
ing the placentas in normal and hypertensive pregnancies
found smaller placentas with abnormal shape, calcifications
and vascular insufficiency in the latter group [133]. Rat re-
search suggests that persistent hypertension during pregnancy
may affect placental development, in turn impacting mamma-
ry development in the dam and milk available to the pups
[134, 135]. Clinically, lactation consultants see women who
were hypertensive during pregnancy or who have persistent
hypertension post-delivery presenting with inadequate
lactogenesis II. A single-case report suggested a relationship
between magnesium sulfate therapy and delayed lactation in a
mother with pregnancy-induced lactation [136], but no further
research has been conducted to confirm or disprove the theory.
Some mothers with histories of hypertensive pregnancies re-
port scant breast changes during the pregnancy, while others
report noticeable breast growth. Despite intensive efforts with
increased feeds, additional pumping and/or galactogogues,
not all of these women reach 100 % milk production. Further
research is needed in order to understand the underlying inter-
ferences and develop treatment plans that address the problem
specifically.
Maternal Nutrition: Does it Matter?
It is well known that proper nutrition is important to good milk
production in dairy cows. Inadequate levels of protein, zinc,
selenium, vitamins A and E increase the risk of subclinical or
clinical mastitis, which in turn causes gap junctions to open
and milk synthesis to drop. Severe or persistent anemia, which
may be caused by deficiencies in protein, iron, copper, cobalt
or selenium, may cause lower milk output. Inadequate fiber
impacts rumen function, gut health and nutrient uptake.
J Mammary Gland Biol Neoplasia
Vitamin B-12 deficiency more rarely may underlie declines
in milk production [137].
Current western wisdom dictates that unless a mother is
severely malnourished, her diet will not significantly impact
the quantity of her milk. Concerned mothers are routinely
reassured that a poor diet will not affect their infant. But can
it affect their milk production? Humans are not cows, but they
still share mammalian roots and traditional wisdom has held a
different view, as echoed by Routh, who commented over a
century ago that Binsufficiency of food must produce insuffi-
ciency of milk [30].^ Jelliffe and Jelliffe wrote one of the best
examinations of this question in 1978, noting a large range of
milk outputs recorded in various countries among populations
of women with differing levels of income and nutrition. They
concluded that while the volume and composition of milk in
poorly nourished women was Bsurprisingly good,^ it was also
often Bsuboptimal in quantity and in quality…^ and noted that
limited studies that supplemented such women resulted in
improved milk output [138]. A recent overview of
galactogogues published in a veterinary journal stated
matter-of-factly that BBreastfeeding is influenced by nutrition-
al and nonnutritional factors… that affect milk synthesis and
secretion [139].^ The idea that diet can make a difference in
milk production seems much more acceptable in the animal
lactation world than in the human lactation world.
Despite receiving little support to investigate nutritional
factors, some mothers looking for answers to their unex-
plained low milk production do explore nutrition. Hilary
Jacobson wrote Mother Food as a compilation of her research
into traditional nutrition wisdom for breastfeeding mothers as
she sought answers to her own struggles with milk production
[140]. The MOBI Motherhood listserv9 that she co-founded
chronicles the struggles and experiences of mothers, with
many compelling anecdotes. One mother described an acci-
dental discovery that on the days she ingested either beans or
psyllium fiber for her constipation, her supply was more abun-
dant and she did not need to supplement her baby. Another
mother with severe chronic low production discovered by
chance that when she ate a certain store-bought carrot muffin,
her pumped milk output would increase for the day. After
several attempts to recreate the muffins at home, she deter-
mined that almond meal was the pivotal ingredient for her.
Almonds are high in calcium, which plays a role in PRL
release [141, 142]. Lactation consultants also report multiple
cases of women who experienced dips in milk production
during menses that improved with calcium-magnesium
supplements.
Other MOBI mothers found Bgreen^ or chlorophyll drinks
containing ingredients such as barley-grass and alfalfa leaf to
be helpful. Such drinks are higher in iron and B-vitamins, and
9
http://www.mobimotherhood.org/mobi-support-group.html
J Mammary Gland Biol Neoplasia
anemia is a known risk factor for lower milk production in
both rats and human mothers [143–145].
A mother with a history of gastric bypass surgery had her
nutritional status checked when she had difficulty making
enough milk for her new baby. Tests revealed that her zinc
was low, and once supplementation was initiated, her produc-
tion soon stabilized. Rat dams who were marginally zinc de-
ficient pre-conception through mid-lactation showed greater
mammary cell apoptosis and decreased milk secretion [146].
A trial of zinc supplementation for normal women did not
increase milk production, but the authors speculated that re-
sults might differ in zinc-deficient mothers [78].
It is easier to believe that nutrition can be a factor for wom-
en in developing countries than it is for women in the western
world, where obesity is epidemic. But in the U.S. especially,
high-fat and low-nutrition foods are cheap and easy to obtain.
When pregnant women were given customized nutritional ad-
vice and treatment, they had fewer adverse perinatal outcomes
than control groups from private practice and community
clinics [147]. Might such targeted nutritional intervention im-
prove lactation for some mothers as well? The anecdotes
above represent individual cases that did not fall into common
boxes for low milk production etiologies. How many more
cases exist that have not been recognized because nutrition
has not been on our radar? Screening women with unex-
plained lactation problems for nutritional deficiencies may
uncover new etiologies that would be easy to address. But
without supportive research, the role of nutrition may continue
to be overlooked.
Methods to Increase Milk Production
Desperate mothers look to their peers and on the internet for
ideas and answers when the gold standard Bfeed-more-often,
pump-more-often, add breast compression^ recommendation
falls short for their situation. Botanical galactogogues, both
food and herbs, are popular despite the lack of scientific evi-
dence to support their use [148]. Women are frequently dis-
couraged by their health care providers from pursuing thera-
pies that have not been proven by studies, while at the same
time there seems to be little academic interest in, let alone
funding for, conducting such research. Thus, mothers such
as the online members of MOBI listserv and the Facebook
IGT and Low Milk Supply Group take matters into their own
hands and create their own files of anecdotal reports to assist
each other. Not knowing for sure what might help, and not
wanting to wait for weeks to trial remedies one by one, many
mothers resort to simultaneously ingesting numerous reputed
galactogogues via capsules, tinctures, teas and foods in a quest
to increase milk production as quickly as possible (Fig. 5e).
We need to determine which herbs and foods might be
most helpful, in what forms they work best, in what dosages
and under what circumstances [149]. For instance, a rat study
of shatavari as a galactogogue tested an aqueous decoction
versus a milk decoction of shatavari as based on traditional
usage and discovered that the milk decoction was 27 % more
effective [150]. Does this mean that a powdered herb capsule
of shatavari, a form favored by western women, may not be
very effective? Clearly, a comprehensive understanding of
each herb or food is necessary when designing such research,
and scientists would be wise to include an expert in botany
with specialized knowledge of the specific plant on their re-
search team. Of equal importance is understanding how a
galactogogue may work as some stimulate milk synthesis di-
rectly while others may work indirectly by addressing an
inhibiting problem such as hyperandrogenism or insulin resis-
tance [151–153]. Underlying etiologies vary, and thus what
works for one mother does not necessarily work for another.
Animal studies would be a good starting point for investigat-
ing these questions. The costs are much lower, making it more
feasible to test multiple forms and dosages of an herb.
While galactogogues are popular and have historic prece-
dent as a potential answer to deficient lactation, there are other
hypothesized avenues for stimulating lactation that are severe-
ly lacking in scientific examination. These include the inges-
tion of placenta (placentophagy) [154, 155], chiropractics/
manual manipulation [156], homeopathy, Transcutaneous
Electrical Nerve Stimulation [157–159], ultrasound [160],
breast massage [161, 162], hypnosis/imagery/relaxation
[163–165] and antenatal expression [166]. Acupuncture has
been studied more extensively [167–170] but the researchers
rarely address the etiology of lactation problems in each case,
or criteria for when acupuncture may or may not be appropri-
ate. Mothers need research-based guidance regarding the ap-
propriate choices, effectiveness and relative benefits and risks
of such alternative therapies.
Summary
The dilemma of primary lactation problems is real, but an-
swers are lacking.10 Mothers seeking help from their health
care providers are frequently pointed to endocrinologists and
reproductive endocrinologists, most of whom are simply not
interested in dealing with lactation concerns, as described in
this recent media posting by one frustrated mother:
I’m super disappointed. I’ve been struggling for over a
month with low milk supply. I made an appointment
with a reproductive endocrinologist 3 weeks ago and
my appointment was supposed to be tomorrow. When
I made the appointment, I specifically asked if they
10
Quinn, E. A. (2014). Who manages the mammaries? http://
biomarkersandmilk.blogspot.com/2013/01/who-manages-
mammaries.html

would take me as a patient because I’m not trying to get
pregnant - but I want to understand what is going on
with my hormones (PCOS) and why my milk supply
is low. Then, today, the day before my appointment, I
got this message: BWe need to cancel your appointment.
In reviewing your information, the doctor didn’t feel he
could address the issues that you are having with your
PCOS in regards to breastfeeding. Our physicians focus
is really on helping patients achieve pregnancy. …He
apologizes for the inconvenience but truly feels your
issues would be better addressed by your OB/GYN.^
If the obstetrician and the reproductive endocrinologist
can’t help her, who can? Mothers who understand the
importance of breastfeeding face insurmountable obsta-
cles in their quest to give their baby the milk that should
be their birthright (Fig. 5f). The gap between current hu-
man lactation knowledge and the complex cases that lac-
tation consultants face with disturbingly increased fre-
quency needs to be closed. Without research-based guid-
ance, mothers are left to experimentation, sometimes at
great expense and unknown risks. Priority research into
these lactation mysteries will help both lactation consul-
tants and medical professionals to better identify and ad-
dress these problems and increase breastfeeding success
rates.
Acknowledgments I would like to thank the mothers of the Low Milk
Supply and IGT Facebook group and the Mothers Overcoming
Breastfeeding Issues (MOBI) listserv for their generosity in sharing their
stories and photos for this article. I would also like to express my gratitude
to Dr. Russ Hovey for help with the preparation of this manuscript as well
as his many insights into individual situations that have helped sharpen
my understanding of the physiology of lactation; progress cannot be made
without such collaboration across the fields and disciplines.
Conflict of interest The author declare that they have no conflict of
interest.
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