Shownotes
Dopamine plays a central role in motivation, reward, learning, and goal pursuit — and in women, it’s deeply influenced by hormones. In this Goalchella episode, we break down the science of the dopamine system and how fluctuations in estrogen and progesterone across the menstrual cycle shape motivation, focus, mood, and behavior.
We explore sex differences in the dopamine system, why many women feel more driven during certain phases of their cycle, and what research shows about estrogen’s powerful role as a neuromodulator. We also touch on how dopamine function changes during perimenopause and menopause, and why lifetime estrogen exposure may be protective for cognition and brain health as we age.
This episode also tackles one of the most misunderstood topics in women’s health: hormonal birth control. We discuss how hormonal contraceptives influence dopamine, reward sensitivity, learning, and mood — why they aren’t inherently “good” or “bad” — and how individual differences determine each woman’s experience. You’ll learn what signs may indicate dopamine dysregulation, how to recognize patterns across your cycle, and practical steps to advocate for yourself with your healthcare provider.
If you’ve ever wondered why your motivation, focus, or reward-seeking behaviors feel cyclical, this conversation will help you understand your brain — and work with it, not against it.
Links/Research Articles:
https://www.sciencedirect.com/science/article/abs/pii/S0091302222000668?via%3Dihub
https://psycnet.apa.org/record/2021-67755-001
https://psycnet.apa.org/record/2022-66870-001
https://pmc.ncbi.nlm.nih.gov/articles/PMC11698485/
https://pmc.ncbi.nlm.nih.gov/articles/PMC10372431/
https://pmc.ncbi.nlm.nih.gov/articles/PMC11908942/
loving the pod? click the follow button, & we'd love if you could leave a review! thank you x 1000 :)
sign up for the free Smart Girl Newspaper!
insta:: @dr.kelsyvickdpt & @wellnessbigsispod
youtube:: @dr.kelsyvickdpt
tiktok:: @dr.kelsyvickdpt & @wellnessbigsispod
Transcripts
Let's start with just an overview of the dopamine system, zooming in on
2
00:01:48,925 --> 00:01:53,215
its involvement in motivation, reward,
pursuit, learning, behavior, and mood.
3
00:01:53,715 --> 00:01:54,675
Emily Hilz: Yeah, great.
4
00:01:55,035 --> 00:02:00,585
So the dopamine system is part of the
brain's reward and motivational system.
5
00:02:00,865 --> 00:02:05,035
Dopamine neurons are primarily
located in the midbrain, which
6
00:02:05,035 --> 00:02:06,355
is in the back of our brains.
7
00:02:06,685 --> 00:02:10,664
And they send projections throughout
various regions of the brain,
8
00:02:10,965 --> 00:02:16,065
including the nucleus, accumbens,
striatum, and the prefrontal cortex.
9
00:02:16,065 --> 00:02:19,954
And dopamine does unique things
in different regions of the brain.
10
00:02:19,954 --> 00:02:23,945
So in the nucleus accumbens, it's
involved in processing primary
11
00:02:23,945 --> 00:02:28,475
rewards, and then that information is
integrated by our prefrontal cortex,
12
00:02:28,475 --> 00:02:33,035
which is our executive control system
to make decisions about when and how
13
00:02:33,035 --> 00:02:38,675
we seek rewards and exert control over
how intensely we seek those rewards.
14
00:02:39,045 --> 00:02:43,695
It's a very integrated system that
impacts pretty much everything that we do.
15
00:02:43,795 --> 00:02:46,285
Learning and memory and motivation.
16
00:02:46,785 --> 00:02:51,225
Kelsy: One thing I have been
interested in is, of course, with
17
00:02:51,235 --> 00:02:52,915
an audience of primarily women.
18
00:02:53,635 --> 00:02:58,615
Are there any differences in how
the dopamine system affects the male
19
00:02:58,615 --> 00:02:59,755
brain compared to the female brain?
20
00:02:59,785 --> 00:03:01,855
Are there any sex differences
that you guys have seen?
21
00:03:01,905 --> 00:03:05,520
Emily Hilz: I would say, in terms
of its basic function, it does work
22
00:03:05,700 --> 00:03:08,310
the same way in males and females.
23
00:03:08,310 --> 00:03:14,170
But an important, sex specific effect
about dopamine is that dopamine neurons
24
00:03:14,170 --> 00:03:19,810
are very estrogen sensitive, which means
that when they're exposed to estrogens,
25
00:03:19,810 --> 00:03:25,850
they fire a lot more rapidly, they release
more dopamine, that means that women are.
26
00:03:26,350 --> 00:03:30,820
Kind of classically considered to be
more sensitive to rewarding stimuli
27
00:03:31,240 --> 00:03:36,040
especially during phases of our cycle
where estrogens might be higher or,
28
00:03:36,140 --> 00:03:39,350
we're taking estrogen replacement
therapies or something like that.
29
00:03:39,720 --> 00:03:45,970
So we do see, more reward seeking
behavior in females compared to males.
30
00:03:46,470 --> 00:03:50,610
Kelsy: That's interesting because one
of the things that caused me to search
31
00:03:50,610 --> 00:03:55,200
out someone like you who's researching
this kind of thing and looking into
32
00:03:55,320 --> 00:03:59,520
hormonal effects on our dopamine
system, was my own experience, I guess
33
00:03:59,520 --> 00:04:03,630
with my own body and my own tracking
and just noticing, especially in that
34
00:04:03,630 --> 00:04:08,460
like early phase of my cycle, after
my period was over, I noticed, okay,
35
00:04:08,460 --> 00:04:09,840
I'm, you know, I'm ready to go again.
36
00:04:09,840 --> 00:04:10,470
I'm back at it.
37
00:04:10,470 --> 00:04:14,760
Let's get, you know, I was way more
motivated, way more disciplined, way more.
38
00:04:15,260 --> 00:04:19,250
goal driven in that phase and I started
realizing, I was like, oh, hang on.
39
00:04:19,310 --> 00:04:21,350
This is kind of happening cyclically.
40
00:04:21,560 --> 00:04:26,810
So you mentioned a little bit how
estrogen and dopamine go hand in hand.
41
00:04:26,840 --> 00:04:30,080
Explain a little bit more about
that, especially in regards to
42
00:04:30,080 --> 00:04:33,850
like the menstrual cycle and how
different high hormone phases and
43
00:04:33,850 --> 00:04:38,760
low hormone phases affect our ability
to be more goal-driven or be more
44
00:04:38,760 --> 00:04:40,230
motivated or be more disciplined.
45
00:04:40,730 --> 00:04:41,060
Emily Hilz: Sure.
46
00:04:41,480 --> 00:04:44,890
So I study these things using rats.
47
00:04:44,950 --> 00:04:47,710
And in rats have what is
called an est extra cycle.
48
00:04:47,760 --> 00:04:51,360
It's very similar conceptually
to the human menstrual cycle.
49
00:04:51,690 --> 00:04:54,720
And the main difference basically
is that rats don't menstruate.
50
00:04:54,720 --> 00:04:59,840
They reabsorb their, you're lining up each
cycle and it only lasts four or five days,
51
00:05:00,080 --> 00:05:04,190
which is great for a research context
because then you can study things in four
52
00:05:04,190 --> 00:05:06,050
or five days instead of over months and
53
00:05:06,208 --> 00:05:06,718
Kelsy: Right,
54
00:05:06,768 --> 00:05:10,238
Emily Hilz: But things that are
pretty well accepted, I would say at
55
00:05:10,238 --> 00:05:13,128
this point in science is that the.
56
00:05:13,508 --> 00:05:19,628
Estro cycle influences how much females
will seek out rewarding stimuli.
57
00:05:19,628 --> 00:05:24,908
So a rat that is in a high estrogen
phase of its cycle will drink a lot more
58
00:05:24,908 --> 00:05:30,618
alcohol, or it will emit like pleasure
calls more rapidly and intensely in
59
00:05:30,618 --> 00:05:35,488
response to what we would call like
dopaminergic or stimulant drugs.
60
00:05:35,488 --> 00:05:37,258
That's what researchers use.
61
00:05:37,258 --> 00:05:40,408
When we study reward, we use rewarding
stimuli, and the most rewarding
62
00:05:40,408 --> 00:05:45,448
stimuli tend to be dopaminergic
drugs like amphetamine or cocaine.
63
00:05:45,948 --> 00:05:50,718
and extra cycle will impact the
way that females will seek out.
64
00:05:51,138 --> 00:05:53,868
Those rewards, how much
they will consume them.
65
00:05:54,188 --> 00:05:57,878
when we talk about motivation, I think
there's sort of two types of motivation.
66
00:05:57,878 --> 00:06:02,868
It would be essentially motivation
in maybe a positive context or
67
00:06:02,868 --> 00:06:07,678
motivation, which could be maladaptive
compulsive rewards seeking.
68
00:06:07,678 --> 00:06:12,058
Higher estrogen phases could be associated
with compulsive behaviors, depending
69
00:06:12,058 --> 00:06:15,578
on a lot of factors going into that.
70
00:06:16,078 --> 00:06:21,123
Kelsy: When we talk about being more
motivated or less motivated, or more
71
00:06:21,123 --> 00:06:25,293
disciplined or less disciplined,
does any of that have to do with how
72
00:06:25,293 --> 00:06:29,883
much more dopamine is released like
a delta between our baseline and our
73
00:06:29,883 --> 00:06:32,673
peak, or our baseline and our valley?
74
00:06:32,678 --> 00:06:34,423
Like if we are someone who has.
75
00:06:35,008 --> 00:06:39,748
I guess more estrogen in one of the
different phases of our cycle, does that
76
00:06:39,748 --> 00:06:45,388
necessarily equate to, I guess, more
dopamine released and more motivation?
77
00:06:45,388 --> 00:06:49,938
Or where our baseline is, does that go
into play where if I am a naturally,
78
00:06:49,938 --> 00:06:54,438
like if my dopamine levels are naturally
a little higher and I happen to, you
79
00:06:54,438 --> 00:06:59,238
know, have maybe a little bit more
estrogen in a certain phase with that,
80
00:06:59,238 --> 00:07:03,228
like I guess the delta between the
two, does that play into it at all?
81
00:07:03,728 --> 00:07:09,628
Emily Hilz: I'm not very familiar with
that kind of level of resolution, but I
82
00:07:09,628 --> 00:07:14,338
think it's interesting that you bring up
the idea of sort of natural differences
83
00:07:14,338 --> 00:07:18,568
between people because there's a huge
amount of difference between individuals
84
00:07:18,568 --> 00:07:21,658
in terms of how much estrogen we release.
85
00:07:21,758 --> 00:07:23,588
Or, the activity of our dopamine systems.
86
00:07:23,588 --> 00:07:26,738
That's why, some people have
a DHD and some people don't.
87
00:07:27,108 --> 00:07:32,258
Not for estrogen, but for, dopamine
and other neuromodulators like that.
88
00:07:32,707 --> 00:07:36,098
And I think that could go back
to early life development.
89
00:07:36,098 --> 00:07:41,758
So maybe you are some body who has
been, through whatever reason, maybe,
90
00:07:41,758 --> 00:07:46,308
just that's something that has emerged
along your genetic line or maybe, in
91
00:07:46,308 --> 00:07:48,468
terms of endocrine disruptor exposure.
92
00:07:48,468 --> 00:07:52,848
But either way, maybe you're somebody
who has higher estrogen levels or during
93
00:07:52,848 --> 00:07:54,828
early life when the brain is developing.
94
00:07:54,828 --> 00:08:01,138
That could certainly lead to, more, I
guess I'll go with activity or sensitivity
95
00:08:01,138 --> 00:08:05,458
in the dopamine system, and that could
certainly impact the way that you.
96
00:08:05,958 --> 00:08:10,598
Experience the world across a huge
domain of areas, be it the way that
97
00:08:10,598 --> 00:08:14,108
you learn how much, how easy it is for
you to pay attention to things, the
98
00:08:14,108 --> 00:08:20,528
motivation that you feel your sensitivity
to, rewarding stimuli and how well you
99
00:08:20,528 --> 00:08:23,913
can we call this top, top-down control.
100
00:08:23,913 --> 00:08:28,893
So the prefrontal cortex exerts
top-down control over the striatal
101
00:08:28,993 --> 00:08:34,643
tissues to stop you from engaging in
maladaptive reward seeking behaviors
102
00:08:34,643 --> 00:08:39,263
that could be like overeating or
drug abuse or anything like that.
103
00:08:39,323 --> 00:08:42,743
Or, and then the alternative to that
is bottom up control, where it's
104
00:08:42,743 --> 00:08:46,523
like the dopamine system is taking
control from the prefrontal cortex.
105
00:08:46,523 --> 00:08:49,433
And that's when you start getting
into compulsive behaviors.
106
00:08:49,793 --> 00:08:53,773
And, know, motivation in that
context would be compulsive.
107
00:08:54,273 --> 00:08:58,353
Kelsy: So flipping gears a little
bit to from the menstrual cycle to
108
00:08:58,353 --> 00:09:01,683
something like menopause, I know
I told you I selfishly want more
109
00:09:01,683 --> 00:09:03,063
people to start thinking about that.
110
00:09:03,063 --> 00:09:05,613
And I know our hormones
change in that period.
111
00:09:05,613 --> 00:09:08,973
And I know this might not directly
correlate with your research, but
112
00:09:09,153 --> 00:09:13,413
what would you say for when we as
women experience or go through the
113
00:09:13,413 --> 00:09:19,923
phase of menopause, how might you
expect that to alter how our brains
114
00:09:19,923 --> 00:09:21,843
and our dopamine systems function?
115
00:09:22,343 --> 00:09:23,618
Emily Hilz: That's a great question.
116
00:09:23,718 --> 00:09:26,958
Again, based on research that
has been performed in rodents,
117
00:09:26,958 --> 00:09:28,778
rats don't go through menopause.
118
00:09:28,808 --> 00:09:34,868
And so we use ectomy
models to model menopause.
119
00:09:35,078 --> 00:09:37,628
This isn't research that I've done
myself, but I'm pretty familiar
120
00:09:37,628 --> 00:09:39,458
with it because that's how we study.
121
00:09:39,508 --> 00:09:44,218
When there are hormones and when there
aren't hormones, in regard to reward,
122
00:09:44,248 --> 00:09:50,248
generally what you see an overpromised
rat, and this is like pretty well
123
00:09:50,248 --> 00:09:57,098
corroborated in human data, is that
removal of endogenous estrogens.
124
00:09:57,128 --> 00:10:05,728
Either via ectomy in a model or in human
women impairs reward signaling processes.
125
00:10:05,728 --> 00:10:07,903
You'll see less motivation for reward.
126
00:10:07,903 --> 00:10:11,098
You'll also see a lot
less behavior in general.
127
00:10:11,098 --> 00:10:14,368
And then moving out of the
basic reward system into more
128
00:10:14,368 --> 00:10:16,258
complex cognitive behavior.
129
00:10:16,528 --> 00:10:22,878
A lot of women, report brain fog
during, menopause perimenopause period.
130
00:10:23,268 --> 00:10:24,438
And that's.
131
00:10:24,938 --> 00:10:29,868
Pretty well established to be due
to reduced estrogen availability.
132
00:10:30,108 --> 00:10:34,108
You have this hormone that is
very synaptically exciting.
133
00:10:34,708 --> 00:10:37,828
What it does is it stimulates a lot
of activity in the brain, not just
134
00:10:37,828 --> 00:10:41,038
in the dopamine system, but across
a lot of different types of neurons.
135
00:10:41,398 --> 00:10:46,328
And so when it's not there it's a
huge change to go through cognitively.
136
00:10:46,468 --> 00:10:50,418
And so I can't even think of, an
example that it wouldn't affect.
137
00:10:50,451 --> 00:10:51,446
Kelsy: Yeah, totally.
138
00:10:51,896 --> 00:10:57,446
I know you also mentioned that possibly
starting it earlier might offset
139
00:10:57,446 --> 00:11:05,606
some of the maybe less desirable
impacts of this lower estrogen phase
140
00:11:05,606 --> 00:11:07,886
in our life a little bit or so.
141
00:11:07,946 --> 00:11:11,786
I guess question one is their benefit to.
142
00:11:12,286 --> 00:11:16,936
Maybe not like waiting it out and letting
my body sort of try and regulate it
143
00:11:17,266 --> 00:11:22,606
when it comes to how our body functions
in that perimenopause menopause phase
144
00:11:22,606 --> 00:11:24,256
with that lower estrogen levels.
145
00:11:24,316 --> 00:11:28,096
And then two, do you expect it to sort
of level out, like, like you said, it's
146
00:11:28,096 --> 00:11:31,096
a drastic change when we go through
something like this where all of a sudden
147
00:11:31,096 --> 00:11:36,076
our body's used to functioning at this
certain level and then it, it drops.
148
00:11:36,106 --> 00:11:38,836
And so do you guys see this change?
149
00:11:38,836 --> 00:11:42,076
And I don't even know if this is
possible to study, I guess long term
150
00:11:42,076 --> 00:11:47,626
after menopause and once your body
starts to reregulate at that, that
151
00:11:47,626 --> 00:11:53,236
new normal, is there sort of this
fluctuation and change longer term too?
152
00:11:53,736 --> 00:11:57,226
Emily Hilz: So to address your
first question, when you say
153
00:11:57,226 --> 00:12:00,496
starting it earlier, you probably
mean like estrogen replacement
154
00:12:00,679 --> 00:12:01,909
Kelsy: Yes, exactly.
155
00:12:02,506 --> 00:12:02,926
Emily Hilz: Yeah.
156
00:12:02,926 --> 00:12:04,806
And i'm not a physician,
157
00:12:05,019 --> 00:12:05,499
Kelsy: Yes.
158
00:12:06,036 --> 00:12:10,296
Emily Hilz: am not making any
physician type recommendations.
159
00:12:10,606 --> 00:12:16,006
But there is certainly a pretty
prevalent theory in the field called
160
00:12:16,006 --> 00:12:22,811
the, lifetime estrogen Exposure theory
which posits that taking, hormonally
161
00:12:22,836 --> 00:12:26,766
active drugs that are meant to be
hormonally active, not things that
162
00:12:26,766 --> 00:12:28,506
are not meant to be hormonally active.
163
00:12:28,506 --> 00:12:30,846
I'm sure we'll get into
that a little bit later.
164
00:12:31,326 --> 00:12:34,806
Can actually improve your
long-term cognitive function.
165
00:12:35,016 --> 00:12:40,676
So women who have taken birth control
pills for longer in their lives, or
166
00:12:40,676 --> 00:12:44,876
women who start estrogen replacement
therapies earlier, consistently
167
00:12:44,876 --> 00:12:50,496
perform better on a host of cognitive
tests and, report better outcomes.
168
00:12:50,996 --> 00:12:54,356
In terms of when you should start,
that's definitely a conversation
169
00:12:54,356 --> 00:12:56,336
to have with your physician.
170
00:12:56,336 --> 00:13:00,916
And I, hopefully there's some, a
physician that's, versed in that field.
171
00:13:01,016 --> 00:13:04,706
Somebody who really does have
expertise in women's health would
172
00:13:04,706 --> 00:13:07,016
be who I would wanna talk to.
173
00:13:07,316 --> 00:13:15,496
But, speaking anecdotally, I have a
friend who is 35 and she was talking to
174
00:13:15,496 --> 00:13:20,936
her doctor, who's a really great doctor,
and she was talking about the brain fog
175
00:13:20,936 --> 00:13:22,886
and exhaustion that she's been feeling.
176
00:13:22,886 --> 00:13:28,436
And the doctor prescribed her a low
level vaginal estrogen cream, and she
177
00:13:28,616 --> 00:13:32,756
has just been raving about how great
it's been and how helpful it's been.
178
00:13:32,756 --> 00:13:35,516
So I think she's one of those
people who maybe has naturally lower
179
00:13:35,516 --> 00:13:37,406
levels at an earlier point in life.
180
00:13:37,796 --> 00:13:38,906
And, jury's out.
181
00:13:38,906 --> 00:13:41,696
We're still in our thirties
right now, so we'll find out.
182
00:13:41,696 --> 00:13:43,976
Hopefully it's gonna work
out really well for her.
183
00:13:44,476 --> 00:13:45,736
It seems to be working well for her.
184
00:13:45,736 --> 00:13:46,096
Now,
185
00:13:46,596 --> 00:13:49,686
Kelsy: And then what about
part two, I guess, of these,
186
00:13:50,121 --> 00:13:50,271
Emily Hilz: two,
187
00:13:50,771 --> 00:13:54,165
Kelsy: Once your body re regulates on
this new level and gets used to that,
188
00:13:54,596 --> 00:13:55,926
what effects do you guys see there?
189
00:13:56,426 --> 00:13:59,540
Emily Hilz: I would say what we tend
to see when we over optimize a female
190
00:13:59,540 --> 00:14:05,581
rat is that it starts responding
more similarly to a male rat.
191
00:14:05,881 --> 00:14:10,991
So while I would say that it's gonna be
a change, it doesn't necessarily have to
192
00:14:10,991 --> 00:14:15,671
be contextualized as maladaptive or bad.
193
00:14:16,091 --> 00:14:19,111
It's just what is the new normal for you.
194
00:14:19,651 --> 00:14:24,151
I am speaking, informally, in that
regard from a human perspective.
195
00:14:24,551 --> 00:14:28,061
But from an animal perspective,
that is what we tend to see is like
196
00:14:28,061 --> 00:14:32,471
when we measure female rats in low
hormone phases, or we over optimize
197
00:14:32,471 --> 00:14:38,040
them, we tend to see them performing
at levels that males perform.
198
00:14:38,161 --> 00:14:44,851
So a female could be up higher in terms of
their cognitive flexibility or motivation,
199
00:14:44,851 --> 00:14:46,741
and then we over optimize them.
200
00:14:46,741 --> 00:14:51,951
And then they are a little lower, but
they're not, below the male population,
201
00:14:51,951 --> 00:14:55,551
they're just lower than they were when
they were in the high estrogen phases.
202
00:14:56,074 --> 00:15:01,264
Kelsy: Comparatively, like before and
after for that same rat or individual.
203
00:15:01,764 --> 00:15:04,254
Emily Hilz: That's hard to say because
usually we do it between groups.
204
00:15:04,467 --> 00:15:05,067
Kelsy: Okay.
205
00:15:05,567 --> 00:15:08,777
Emily Hilz: Yeah, I've never really done
that type of study where we looked at
206
00:15:08,777 --> 00:15:11,087
before and after in the same animal.
207
00:15:11,137 --> 00:15:14,137
Instead it would be like this group
of animals was high estrogen, this
208
00:15:14,137 --> 00:15:15,757
group of animals was over optimiz.
209
00:15:15,757 --> 00:15:19,807
And then we also had a group of males and
we compared cognitive and motivational
210
00:15:19,807 --> 00:15:26,217
outcomes in those types of animals to see
how estrogen levels impact different types
211
00:15:26,217 --> 00:15:30,567
of behavior in the realm of cognitive
attentional function and motivation.
212
00:15:31,067 --> 00:15:33,982
Kelsy: You also, I know a lot of
your research focuses on hormonal
213
00:15:33,982 --> 00:15:36,922
contraceptives specifically, and we
kind of skipped over that part, but I
214
00:15:36,922 --> 00:15:38,632
definitely wanna cover that as well too.
215
00:15:38,632 --> 00:15:44,092
So, what role do hormonal contraceptives
play specifically for like younger
216
00:15:44,092 --> 00:15:48,202
women, twenties, thirties, those who
might be on a hormonal contraceptive?
217
00:15:48,202 --> 00:15:53,692
What role do those play within our brains
as it relates to the dopamine system?
218
00:15:54,192 --> 00:15:58,762
Emily Hilz: Yeah, I will, caveat,
I studied hormonal contraception in
219
00:15:58,762 --> 00:16:02,482
graduate school, and then I've moved on
to studying endocrine disruptors now.
220
00:16:02,482 --> 00:16:07,222
So it's not really an active research
line that I'm continuing to pursue, but
221
00:16:07,222 --> 00:16:11,692
I do hope to come back to it because it
was something I was always working for.
222
00:16:11,692 --> 00:16:13,222
It's so relevant for women.
223
00:16:13,222 --> 00:16:14,602
It's so interesting.
224
00:16:15,102 --> 00:16:22,032
but not very predominantly studied
in women's health research or just,
225
00:16:22,032 --> 00:16:29,122
in neuroscience research aiming to
characterize the, female neuroscientific
226
00:16:29,122 --> 00:16:32,982
perspective, which there's a big
movement which has been going on for
227
00:16:32,982 --> 00:16:38,462
decades of, sex as a biological variable
and including females in biomedical
228
00:16:38,462 --> 00:16:44,642
research to improve our standards and
drug manufacturing and recommendations.
229
00:16:45,142 --> 00:16:50,292
And I'm going try not to get on a tangent
here, but I will say that initiative has
230
00:16:50,292 --> 00:16:53,292
been in place at the NIH for decades.
231
00:16:53,292 --> 00:16:57,582
And you still see tons of experiments
that are only done in males and
232
00:16:57,582 --> 00:17:01,182
they'll say, oh, we didn't wanna use
females because they're variable,
233
00:17:01,182 --> 00:17:02,802
because they have est extra cycles.
234
00:17:02,802 --> 00:17:04,722
And it's that's not even always true.
235
00:17:05,222 --> 00:17:09,031
And so that's an aside a
different conversation, but,
236
00:17:09,734 --> 00:17:11,720
Kelsy: Hey, I'm in the same mindset.
237
00:17:11,720 --> 00:17:17,190
I do a lot of just education in general,
and I'm a women's health pt, so I do a lot
238
00:17:17,190 --> 00:17:22,740
of women's health work and I try and get
on a lot of researchers and scientists and
239
00:17:22,740 --> 00:17:27,300
people who are willing to go through the
hard efforts and study women specifically.
240
00:17:27,300 --> 00:17:29,870
So, and given all of our phases, right?
241
00:17:29,870 --> 00:17:33,650
I mean, it's so hard to study
women in general anyways, because
242
00:17:33,650 --> 00:17:36,950
of our menstrual cycles and the
variability within that pregnancy.
243
00:17:36,950 --> 00:17:41,330
Who knows whether or not, I'm sure like
the people that you might be studying if
244
00:17:41,330 --> 00:17:44,780
you are doing human studies, are maybe
going to get pregnant and then all of
245
00:17:44,780 --> 00:17:46,430
a sudden there's a new variable that.
246
00:17:46,670 --> 00:17:50,060
You might not have been able, like
you might not have thought to exclude
247
00:17:50,060 --> 00:17:53,840
early on and then add in hormonal
contraceptives and things like that too.
248
00:17:53,840 --> 00:17:58,490
So it's, it's complex and complicated
and we are complicated and complex, but
249
00:17:58,700 --> 00:18:02,540
we deserve to, to be studied and to be
incorporated in studies in all of our,
250
00:18:02,540 --> 00:18:08,060
many phases of our lives so that we can
have better knowledge of our bodies.
251
00:18:08,060 --> 00:18:11,600
And then yeah, subsequent better
care from a variety of, of
252
00:18:11,600 --> 00:18:13,550
healthcare providers and industries.
253
00:18:14,050 --> 00:18:19,070
Emily Hilz: Yeah, I definitely have a lot
of thoughts about this specifically that
254
00:18:19,570 --> 00:18:23,010
I won't go into too much, but I'll say,
a part of the thing is like you have the
255
00:18:23,010 --> 00:18:25,320
variation of hormones over the cycle.
256
00:18:25,320 --> 00:18:28,380
So if you have an experimental
group, a lot of the reasons that
257
00:18:28,380 --> 00:18:33,750
females get excluded from research
is because they're so variable, quote
258
00:18:33,750 --> 00:18:36,150
unquote, because of their cycle.
259
00:18:36,150 --> 00:18:39,750
But if you have a well powered
experiment, you could take these,
260
00:18:39,780 --> 00:18:43,230
an animal experiment, let's say,
and you have enough animals in it,
261
00:18:43,230 --> 00:18:46,020
then that creates an average, and
that would be your female average
262
00:18:46,020 --> 00:18:47,970
from across all phases of the cycle.
263
00:18:47,970 --> 00:18:52,915
So I think it's a cop out personally
in terms of, I think there's
264
00:18:52,915 --> 00:18:56,035
nothing wrong with focusing on
one sex for a research question.
265
00:18:56,445 --> 00:18:59,575
But I think if the only reason that
you're doing that is because you.
266
00:19:00,075 --> 00:19:03,725
Don't want to with including the
other sex, then I don't think
267
00:19:03,725 --> 00:19:05,315
that's a great reason to do it.
268
00:19:05,555 --> 00:19:08,965
But we'll get back to hormonal
contraception cause that's what
269
00:19:08,965 --> 00:19:10,705
we're talking about right now.
270
00:19:11,205 --> 00:19:16,845
So you were asking me about motivation,
the dopamine system, contraceptives.
271
00:19:17,145 --> 00:19:23,145
The thing with hormonal contraception
is that there's not a lot of preclinical
272
00:19:23,295 --> 00:19:28,485
or even human epidemiological data
about its effects outside of, the
273
00:19:28,485 --> 00:19:30,845
reproductive ones that it's used for.
274
00:19:31,185 --> 00:19:37,985
And in the last, I would say maybe 10
years, realistically, like five years,
275
00:19:38,135 --> 00:19:42,145
there've been a lot more researchers
studying hormonal contraception.
276
00:19:42,195 --> 00:19:47,055
There's someone I know named Jesse
LACAs who is really spearheading
277
00:19:47,175 --> 00:19:50,145
the neurobehavioral research in.
278
00:19:50,580 --> 00:19:55,250
Hormonal contraceptive use, who's so
impressive and doing a bunch of stuff.
279
00:19:55,380 --> 00:20:00,510
And we collaborated a little bit to
write a review of like how to study these
280
00:20:00,610 --> 00:20:03,040
synthetic hormones in animal models.
281
00:20:03,660 --> 00:20:09,110
But I wanted to study it specifically
because I was previously studying just
282
00:20:09,110 --> 00:20:15,290
the general esra cycle phases and how
they contribute to how females learn.
283
00:20:15,770 --> 00:20:20,840
And what I was studying was how the
female brain represents context.
284
00:20:21,140 --> 00:20:28,860
So if you are of familiar with the
idea of let's say if you study in a
285
00:20:28,860 --> 00:20:35,030
certain context like chew gum or you
study at the library, be able to recall
286
00:20:35,030 --> 00:20:38,905
information better when you're tested on
it later if you're in that same context.
287
00:20:39,778 --> 00:20:42,688
And that all happens in the hippocampus,
which is another region of the brain
288
00:20:42,718 --> 00:20:45,388
that's very sensitive to estrogen.
289
00:20:45,448 --> 00:20:49,628
And so I was interested to know how
estrogen levels across the cycle
290
00:20:49,748 --> 00:20:52,118
impacted context representation.
291
00:20:52,178 --> 00:20:56,338
And I found that female rats were
better at encoding context and
292
00:20:56,338 --> 00:21:00,238
differentiating between context when
they were tested in high hormone
293
00:21:00,238 --> 00:21:03,788
levels or when they learned in a high
hormone level and then were tested
294
00:21:03,838 --> 00:21:05,448
in a different phase of their cycle.
295
00:21:05,448 --> 00:21:10,278
So it was like the cycle was acting
as its own context basically, which
296
00:21:10,278 --> 00:21:11,928
called this like an internal context.
297
00:21:11,928 --> 00:21:15,248
It's oh, when I'm stressed out,
suddenly I, stress is an internal
298
00:21:15,248 --> 00:21:17,408
state, those types of things.
299
00:21:17,828 --> 00:21:22,658
And so I started thinking about
hormonal contraception as this
300
00:21:23,158 --> 00:21:28,018
internal context that we put
ourselves in for long periods of time.
301
00:21:28,518 --> 00:21:34,048
What happens when that context changes is
the perspective I was taking when I was
302
00:21:34,048 --> 00:21:39,538
first studying hormonal contraception was
does it create its own internal context?
303
00:21:39,538 --> 00:21:43,938
Does that help learn or encode
information or how do changes in it
304
00:21:44,028 --> 00:21:46,098
help us learn or encode information?
305
00:21:46,598 --> 00:21:50,828
so I think I would say it's a dual
perspective in my research of one,
306
00:21:51,188 --> 00:21:55,958
how does modulating our hormone levels
synthetically impact the way that
307
00:21:55,958 --> 00:21:58,688
we encode and recall information?
308
00:21:58,688 --> 00:22:04,438
And then two, does that hormone state
that is exogenously being manipulated,
309
00:22:04,708 --> 00:22:07,768
create an internal context and
then how does that also influence
310
00:22:07,768 --> 00:22:10,168
the way that we learn and recall?
311
00:22:10,668 --> 00:22:13,248
and I found a couple
of interesting things.
312
00:22:13,318 --> 00:22:17,128
One thing that I found was that the
rats on hormones, so I was comparing
313
00:22:17,128 --> 00:22:19,918
basically a low phase estrogen.
314
00:22:20,418 --> 00:22:26,198
Cycle rat to a high phase rat and then a
contraceptive rat having them go through
315
00:22:26,198 --> 00:22:29,088
some reward learning and memory tests.
316
00:22:29,328 --> 00:22:34,618
And I found that the hormonal
contraception rat was performing pretty
317
00:22:34,618 --> 00:22:38,458
much at the same level that the low
estrogen phase rat was performing.
318
00:22:38,698 --> 00:22:41,098
And they were both lower
than the high phase rat.
319
00:22:41,098 --> 00:22:44,158
And what I was testing
them for was a memory of an
320
00:22:44,158 --> 00:22:46,228
amphetamine associated context.
321
00:22:46,258 --> 00:22:49,318
So I was testing how much they
preferred the amphetamine, how well they
322
00:22:49,318 --> 00:22:53,068
remembered the context, they learned
it in, how well they extinguished
323
00:22:53,068 --> 00:22:55,018
their preference for the amphetamine.
324
00:22:55,018 --> 00:22:59,618
And then I also looked at dopamine
cell numbers and activity in their
325
00:22:59,618 --> 00:23:02,138
brains after the study was finished.
326
00:23:02,638 --> 00:23:08,408
And so the contraceptive rats were
performing similar to the low hormone
327
00:23:08,408 --> 00:23:13,828
rats in terms of they didn't prefer the
amphetamine as much, they still preferred
328
00:23:13,828 --> 00:23:18,078
it because it's still a pretty stimulating
drug, but not as much as the rats that
329
00:23:18,078 --> 00:23:22,688
were in the high estrogen phase, which
sort of suggests that reduction in hormone
330
00:23:22,688 --> 00:23:28,328
levels was impacting their preference
and then they extinguished easier.
331
00:23:28,568 --> 00:23:32,668
And then at the end of the study,
when I was looking at their dopamine
332
00:23:33,028 --> 00:23:37,438
activity, they also had lower dopamine
activity levels compared to the
333
00:23:37,438 --> 00:23:40,708
high estrogen rat, but they were
similar to the low estrogen rat.
334
00:23:41,008 --> 00:23:45,438
And this is something that I think,
we got into before where thinking
335
00:23:45,438 --> 00:23:49,268
about the context that we talk about
hormonal contraception, because.
336
00:23:49,768 --> 00:23:55,858
my research experience, I haven't
found it to be harmful necessarily.
337
00:23:55,858 --> 00:24:00,628
It's just, it's the same as getting used
to, perimenopause or something where
338
00:24:00,628 --> 00:24:03,988
they're performing at the same level
as the rat and it's low estrogen phase.
339
00:24:03,988 --> 00:24:06,478
They're not showing strong impairments.
340
00:24:06,478 --> 00:24:08,808
They're just not as
the high estrogen base.
341
00:24:09,308 --> 00:24:10,268
Kelsy: It's what you compare it to.
342
00:24:10,268 --> 00:24:11,408
And I like how you said that.
343
00:24:11,408 --> 00:24:14,768
'cause it's like, okay, positive versus
negative, you have to have a comparison
344
00:24:14,768 --> 00:24:20,438
value anyways between, is this a positive
behavior due to it or is it a negative?
345
00:24:20,438 --> 00:24:22,478
Well, we don't know unless we
have something to compare it to.
346
00:24:22,568 --> 00:24:26,828
And I also like how you corrected me
as we were just kind of talking before
347
00:24:26,828 --> 00:24:31,168
about how initially we can think of
hormonal contraceptives and their effect
348
00:24:31,168 --> 00:24:34,108
on the dopamine system as maybe a.
349
00:24:34,823 --> 00:24:37,433
You know, my words not
yours, negative thing.
350
00:24:37,523 --> 00:24:41,363
And you had said, and correct me
saying, you know, it just depends on
351
00:24:41,363 --> 00:24:45,743
the context that we talk about it in
where if we're talking about how we can
352
00:24:45,773 --> 00:24:51,463
lower some of the pursuit or goal-driven
behaviors in someone who has more
353
00:24:51,613 --> 00:24:54,463
maladaptive behaviors, like possibly
an addiction or things like that,
354
00:24:54,463 --> 00:24:56,373
like that is a great context for that.
355
00:24:56,373 --> 00:25:01,203
So I like how you, phrase different
things to let us know it's not a
356
00:25:01,203 --> 00:25:03,983
good or bad thing, it's just how
our bodies are functioning in this
357
00:25:03,983 --> 00:25:06,623
new state or in this new context.
358
00:25:06,813 --> 00:25:10,053
Whether or not we are on hormonal
contraceptives or not, or whether we are
359
00:25:10,053 --> 00:25:11,973
on estrogen replacement therapy or not.
360
00:25:12,473 --> 00:25:12,893
Emily Hilz: Yeah.
361
00:25:12,893 --> 00:25:16,433
I really had a great conversation with Dr.
362
00:25:16,433 --> 00:25:20,003
Andrea Gore, who is my
mentor here at UT Austin.
363
00:25:20,103 --> 00:25:23,023
When I was first joining her
lab, I was telling her, I kind
364
00:25:23,023 --> 00:25:27,333
of wanna continue studying
hormonal contraception in the lab.
365
00:25:27,333 --> 00:25:31,233
And she wasn't discouraging me from doing
it, but she did say something to me that
366
00:25:31,233 --> 00:25:34,523
has stuck with me strongly ever since.
367
00:25:34,573 --> 00:25:38,743
This is a politically
charged field in some ways.
368
00:25:38,773 --> 00:25:43,833
And if you frame your research,
like a lot of people when they do
369
00:25:43,833 --> 00:25:45,513
research, they here's the problem.
370
00:25:45,513 --> 00:25:47,553
This is a problem, this is bad.
371
00:25:48,053 --> 00:25:53,353
And we live in a climate where
there are parties who are interested
372
00:25:53,353 --> 00:25:56,623
in skewing the things that you
say to say, okay, maybe if.
373
00:25:57,238 --> 00:26:01,138
Hormonal contraception is so
bad that we shouldn't have it,
374
00:26:01,708 --> 00:26:04,248
which is probably not great.
375
00:26:04,748 --> 00:26:08,998
At least that's not the stance that I
take and then also talking, when you
376
00:26:08,998 --> 00:26:12,718
were talking about substance use, like
that was actually a huge motivation
377
00:26:12,718 --> 00:26:17,718
for me in studying it because I was
really interested in how contraceptives
378
00:26:17,718 --> 00:26:22,885
would impact substance abuse treatment.
379
00:26:23,385 --> 00:26:27,405
with the idea being that if you are
somebody who has like a substance use
380
00:26:27,405 --> 00:26:33,855
disorder and maybe you are or are not
on hormonal contraception at the time
381
00:26:33,855 --> 00:26:38,895
that you developed this disorder, how
would changes in your contraception
382
00:26:38,895 --> 00:26:42,945
availability during treatment and then
later with your finished treatment
383
00:26:42,945 --> 00:26:46,635
and go back into the world, how
might that impact your likelihood
384
00:26:46,635 --> 00:26:51,555
of having a long-term successful
outcome with substance abuse disorder?
385
00:26:51,965 --> 00:26:55,355
Thinking from the perspective that
maybe when you go for treatment, you
386
00:26:55,355 --> 00:26:59,435
might not have it available anymore,
or maybe it becomes available and that
387
00:26:59,435 --> 00:27:03,815
creates a new internal context for you
that changes your treatment outcomes.
388
00:27:03,815 --> 00:27:07,225
And then if you go back out into the
world and whatever that availability
389
00:27:07,225 --> 00:27:09,865
is, goes back to how it used to
be, that could even act as like
390
00:27:09,865 --> 00:27:12,925
a internal trigger for relapse.
391
00:27:13,425 --> 00:27:13,695
Kelsy: Totally.
392
00:27:13,695 --> 00:27:19,545
And thinking of it not as like just
in the context of birth control, but
393
00:27:19,545 --> 00:27:24,285
also it affects a lot of other systems
positively within our bodies too.
394
00:27:24,465 --> 00:27:28,605
And I'm saying this now and I don't
have the research to back it up, but
395
00:27:28,605 --> 00:27:32,955
I have been told that a decreased risk
of a certain type of cancer, and I'm
396
00:27:32,955 --> 00:27:36,795
forgetting the type of cancer, but a
reproductive cancer and having hormonal
397
00:27:36,795 --> 00:27:39,705
contraceptives earlier on can reduce
your risk for that kind of thing.
398
00:27:39,705 --> 00:27:45,135
So just thinking of it, not always
in the context of what we are told,
399
00:27:45,675 --> 00:27:48,465
I guess it's for, and thinking
of it, like you said, for other.
400
00:27:48,965 --> 00:27:53,375
Ways to help people that are struggling
with other types of things, because
401
00:27:53,375 --> 00:27:57,695
estrogen does affect a lot of systems
within our body, just like dopamine does.
402
00:27:57,695 --> 00:28:00,065
And if dopamine and estrogen are
related, how can we use the two
403
00:28:00,065 --> 00:28:02,645
to, to help people in other ways?
404
00:28:02,645 --> 00:28:04,505
So I love that, that you
were looking into that.
405
00:28:05,005 --> 00:28:08,735
Emily Hilz: Yeah, I would say my career
is defined by thinking about things
406
00:28:08,965 --> 00:28:10,935
outside of the way that we were like.
407
00:28:11,435 --> 00:28:13,895
Educated early on to think about them.
408
00:28:13,895 --> 00:28:17,015
So I think of estrogen, not
as a reproductive hormone,
409
00:28:17,015 --> 00:28:18,515
but as a neuromodulator.
410
00:28:18,515 --> 00:28:22,135
And I think of it as an internal
context and I think of it, as
411
00:28:22,175 --> 00:28:26,405
something that drives development,
or, thinking of hormonal contraception
412
00:28:26,405 --> 00:28:30,755
outside of their efficacy for birth
control, but also in the brain really
413
00:28:30,810 --> 00:28:33,160
and beyond in terms of behavior.
414
00:28:33,550 --> 00:28:40,590
But yeah, that positive spin is,
I think part of the misconception
415
00:28:40,590 --> 00:28:42,015
around birth control use.
416
00:28:42,515 --> 00:28:47,545
I would say right now there's a big
conversation around endocrine disruptors.
417
00:28:47,545 --> 00:28:51,025
And so I think the natural progression
of thought is, oh, if you take
418
00:28:51,025 --> 00:28:54,385
something that impacts your hormone
levels, that has to be bad, right?
419
00:28:54,385 --> 00:28:56,635
But endocrine disruptors
are not pharmaceutical.
420
00:28:56,635 --> 00:28:58,255
They're not designed to do that.
421
00:28:58,525 --> 00:29:00,955
And like you wouldn't take
hormonal contraception when
422
00:29:00,955 --> 00:29:02,215
you're actively pregnant.
423
00:29:02,245 --> 00:29:05,155
That would be a bad time to do it.
424
00:29:05,655 --> 00:29:09,245
But women who take them I think
about 10% of women who take hormonal
425
00:29:09,245 --> 00:29:13,171
contraception sort of mood disorders.
426
00:29:13,281 --> 00:29:17,511
But also a very appreciable
number of women report improved
427
00:29:17,511 --> 00:29:20,011
mood and various outcomes.
428
00:29:20,011 --> 00:29:22,771
I'm gonna focus on mood 'cause that's
the one I've read the most about.
429
00:29:22,871 --> 00:29:25,361
so they're certainly helpful for
people and that's all down to
430
00:29:25,361 --> 00:29:29,531
individual differences and finding
right type of contraception for you.
431
00:29:29,531 --> 00:29:30,761
And maybe there isn't one.
432
00:29:31,181 --> 00:29:33,636
For some people it might
be better not to use it.
433
00:29:38,886 --> 00:29:42,546
It's got a little bit of a hurdle to
use, but once it gets working, it works
434
00:29:42,546 --> 00:29:44,916
great, I think, and it's just very.
435
00:29:45,666 --> 00:29:50,616
No frill science forward I wasn't
trying to influence people's opinions.
436
00:29:50,616 --> 00:29:53,826
I just wanted them to have
information when I made it.
437
00:29:53,916 --> 00:29:54,366
So
438
00:29:54,979 --> 00:29:56,974
Kelsy: You get that it reads that way.
439
00:29:56,974 --> 00:30:01,414
And I will say, when you said, I forget
the words you used to describe it, but
440
00:30:01,414 --> 00:30:06,784
not basically not the most tech forward
platform and like being, what did you say?
441
00:30:06,784 --> 00:30:10,024
Like old two thousands old, you
know, two thousands based computer,
442
00:30:10,024 --> 00:30:13,024
like it is a little bit nostalgic
and I actually really liked that.
443
00:30:13,024 --> 00:30:15,274
So I liked using it that way.
444
00:30:15,274 --> 00:30:17,524
I liked logging on and being
like, oh my gosh, wait, this
445
00:30:17,524 --> 00:30:20,134
is so simple as a user to use.
446
00:30:20,134 --> 00:30:21,184
So I loved it.
