Goalchella:: Motivation, learning, and the female brain with Dr. Emily Hilz (A deep dive into reward systems & hormonal influences)

Kelsy: 00:01:44

Let's start with just an overview of the dopamine system, zooming in on

2

: 00:01:48

its involvement in motivation, reward,

pursuit, learning, behavior, and mood.

3

: 00:01:53

Emily Hilz: Yeah, great.

4

: 00:01:55

So the dopamine system is part of the

brain's reward and motivational system.

5

: 00:02:00

Dopamine neurons are primarily

located in the midbrain, which

6

: 00:02:05

is in the back of our brains.

7

: 00:02:06

And they send projections throughout

various regions of the brain,

8

: 00:02:10

including the nucleus, accumbens,

striatum, and the prefrontal cortex.

9

: 00:02:16

And dopamine does unique things

in different regions of the brain.

10

: 00:02:19

So in the nucleus accumbens, it's

involved in processing primary

11

: 00:02:23

rewards, and then that information is

integrated by our prefrontal cortex,

12

: 00:02:28

which is our executive control system

to make decisions about when and how

13

: 00:02:33

we seek rewards and exert control over

how intensely we seek those rewards.

14

: 00:02:39

It's a very integrated system that

impacts pretty much everything that we do.

15

: 00:02:43

Learning and memory and motivation.

16

: 00:02:46

Kelsy: One thing I have been

interested in is, of course, with

17

: 00:02:51

an audience of primarily women.

18

: 00:02:53

Are there any differences in how

the dopamine system affects the male

19

: 00:02:58

brain compared to the female brain?

20

: 00:02:59

Are there any sex differences

that you guys have seen?

21

: 00:03:01

Emily Hilz: I would say, in terms

of its basic function, it does work

22

: 00:03:05

the same way in males and females.

23

: 00:03:08

But an important, sex specific effect

about dopamine is that dopamine neurons

24

: 00:03:14

are very estrogen sensitive, which means

that when they're exposed to estrogens,

25

: 00:03:19

they fire a lot more rapidly, they release

more dopamine, that means that women are.

26

: 00:03:26

Kind of classically considered to be

more sensitive to rewarding stimuli

27

: 00:03:31

especially during phases of our cycle

where estrogens might be higher or,

28

: 00:03:36

we're taking estrogen replacement

therapies or something like that.

29

: 00:03:39

So we do see, more reward seeking

behavior in females compared to males.

30

: 00:03:46

Kelsy: That's interesting because one

of the things that caused me to search

31

: 00:03:50

out someone like you who's researching

this kind of thing and looking into

32

: 00:03:55

hormonal effects on our dopamine

system, was my own experience, I guess

33

: 00:03:59

with my own body and my own tracking

and just noticing, especially in that

34

: 00:04:03

like early phase of my cycle, after

my period was over, I noticed, okay,

35

: 00:04:08

I'm, you know, I'm ready to go again.

36

: 00:04:09

I'm back at it.

37

: 00:04:10

Let's get, you know, I was way more

motivated, way more disciplined, way more.

38

: 00:04:15

goal driven in that phase and I started

realizing, I was like, oh, hang on.

39

: 00:04:19

This is kind of happening cyclically.

40

: 00:04:21

So you mentioned a little bit how

estrogen and dopamine go hand in hand.

41

: 00:04:26

Explain a little bit more about

that, especially in regards to

42

: 00:04:30

like the menstrual cycle and how

different high hormone phases and

43

: 00:04:33

low hormone phases affect our ability

to be more goal-driven or be more

44

: 00:04:38

motivated or be more disciplined.

45

: 00:04:40

Emily Hilz: Sure.

46

: 00:04:41

So I study these things using rats.

47

: 00:04:44

And in rats have what is

called an est extra cycle.

48

: 00:04:47

It's very similar conceptually

to the human menstrual cycle.

49

: 00:04:51

And the main difference basically

is that rats don't menstruate.

50

: 00:04:54

They reabsorb their, you're lining up each

cycle and it only lasts four or five days,

51

: 00:05:00

which is great for a research context

because then you can study things in four

52

: 00:05:04

or five days instead of over months and

53

: 00:05:06

Kelsy: Right,

54

: 00:05:06

Emily Hilz: But things that are

pretty well accepted, I would say at

55

: 00:05:10

this point in science is that the.

56

: 00:05:13

Estro cycle influences how much females

will seek out rewarding stimuli.

57

: 00:05:19

So a rat that is in a high estrogen

phase of its cycle will drink a lot more

58

: 00:05:24

alcohol, or it will emit like pleasure

calls more rapidly and intensely in

59

: 00:05:30

response to what we would call like

dopaminergic or stimulant drugs.

60

: 00:05:35

That's what researchers use.

61

: 00:05:37

When we study reward, we use rewarding

stimuli, and the most rewarding

62

: 00:05:40

stimuli tend to be dopaminergic

drugs like amphetamine or cocaine.

63

: 00:05:45

and extra cycle will impact the

way that females will seek out.

64

: 00:05:51

Those rewards, how much

they will consume them.

65

: 00:05:54

when we talk about motivation, I think

there's sort of two types of motivation.

66

: 00:05:57

It would be essentially motivation

in maybe a positive context or

67

: 00:06:02

motivation, which could be maladaptive

compulsive rewards seeking.

68

: 00:06:07

Higher estrogen phases could be associated

with compulsive behaviors, depending

69

: 00:06:12

on a lot of factors going into that.

70

: 00:06:16

Kelsy: When we talk about being more

motivated or less motivated, or more

71

: 00:06:21

disciplined or less disciplined,

does any of that have to do with how

72

: 00:06:25

much more dopamine is released like

a delta between our baseline and our

73

: 00:06:29

peak, or our baseline and our valley?

74

: 00:06:32

Like if we are someone who has.

75

: 00:06:35

I guess more estrogen in one of the

different phases of our cycle, does that

76

: 00:06:39

necessarily equate to, I guess, more

dopamine released and more motivation?

77

: 00:06:45

Or where our baseline is, does that go

into play where if I am a naturally,

78

: 00:06:49

like if my dopamine levels are naturally

a little higher and I happen to, you

79

: 00:06:54

know, have maybe a little bit more

estrogen in a certain phase with that,

80

: 00:06:59

like I guess the delta between the

two, does that play into it at all?

81

: 00:07:03

Emily Hilz: I'm not very familiar with

that kind of level of resolution, but I

82

: 00:07:09

think it's interesting that you bring up

the idea of sort of natural differences

83

: 00:07:14

between people because there's a huge

amount of difference between individuals

84

: 00:07:18

in terms of how much estrogen we release.

85

: 00:07:21

Or, the activity of our dopamine systems.

86

: 00:07:23

That's why, some people have

a DHD and some people don't.

87

: 00:07:27

Not for estrogen, but for, dopamine

and other neuromodulators like that.

88

: 00:07:32

And I think that could go back

to early life development.

89

: 00:07:36

So maybe you are some body who has

been, through whatever reason, maybe,

90

: 00:07:41

just that's something that has emerged

along your genetic line or maybe, in

91

: 00:07:46

terms of endocrine disruptor exposure.

92

: 00:07:48

But either way, maybe you're somebody

who has higher estrogen levels or during

93

: 00:07:52

early life when the brain is developing.

94

: 00:07:54

That could certainly lead to, more, I

guess I'll go with activity or sensitivity

95

: 00:08:01

in the dopamine system, and that could

certainly impact the way that you.

96

: 00:08:05

Experience the world across a huge

domain of areas, be it the way that

97

: 00:08:10

you learn how much, how easy it is for

you to pay attention to things, the

98

: 00:08:14

motivation that you feel your sensitivity

to, rewarding stimuli and how well you

99

: 00:08:20

can we call this top, top-down control.

100

: 00:08:23

So the prefrontal cortex exerts

top-down control over the striatal

101

: 00:08:28

tissues to stop you from engaging in

maladaptive reward seeking behaviors

102

: 00:08:34

that could be like overeating or

drug abuse or anything like that.

103

: 00:08:39

Or, and then the alternative to that

is bottom up control, where it's

104

: 00:08:42

like the dopamine system is taking

control from the prefrontal cortex.

105

: 00:08:46

And that's when you start getting

into compulsive behaviors.

106

: 00:08:49

And, know, motivation in that

context would be compulsive.

107

: 00:08:54

Kelsy: So flipping gears a little

bit to from the menstrual cycle to

108

: 00:08:58

something like menopause, I know

I told you I selfishly want more

109

: 00:09:01

people to start thinking about that.

110

: 00:09:03

And I know our hormones

change in that period.

111

: 00:09:05

And I know this might not directly

correlate with your research, but

112

: 00:09:09

what would you say for when we as

women experience or go through the

113

: 00:09:13

phase of menopause, how might you

expect that to alter how our brains

114

: 00:09:19

and our dopamine systems function?

115

: 00:09:22

Emily Hilz: That's a great question.

116

: 00:09:23

Again, based on research that

has been performed in rodents,

117

: 00:09:26

rats don't go through menopause.

118

: 00:09:28

And so we use ectomy

models to model menopause.

119

: 00:09:35

This isn't research that I've done

myself, but I'm pretty familiar

120

: 00:09:37

with it because that's how we study.

121

: 00:09:39

When there are hormones and when there

aren't hormones, in regard to reward,

122

: 00:09:44

generally what you see an overpromised

rat, and this is like pretty well

123

: 00:09:50

corroborated in human data, is that

removal of endogenous estrogens.

124

: 00:09:57

Either via ectomy in a model or in human

women impairs reward signaling processes.

125

: 00:10:05

You'll see less motivation for reward.

126

: 00:10:07

You'll also see a lot

less behavior in general.

127

: 00:10:11

And then moving out of the

basic reward system into more

128

: 00:10:14

complex cognitive behavior.

129

: 00:10:16

A lot of women, report brain fog

during, menopause perimenopause period.

130

: 00:10:23

And that's.

131

: 00:10:24

Pretty well established to be due

to reduced estrogen availability.

132

: 00:10:30

You have this hormone that is

very synaptically exciting.

133

: 00:10:34

What it does is it stimulates a lot

of activity in the brain, not just

134

: 00:10:37

in the dopamine system, but across

a lot of different types of neurons.

135

: 00:10:41

And so when it's not there it's a

huge change to go through cognitively.

136

: 00:10:46

And so I can't even think of, an

example that it wouldn't affect.

137

: 00:10:50

Kelsy: Yeah, totally.

138

: 00:10:51

I know you also mentioned that possibly

starting it earlier might offset

139

: 00:10:57

some of the maybe less desirable

impacts of this lower estrogen phase

140

: 00:11:05

in our life a little bit or so.

141

: 00:11:07

I guess question one is their benefit to.

142

: 00:11:12

Maybe not like waiting it out and letting

my body sort of try and regulate it

143

: 00:11:17

when it comes to how our body functions

in that perimenopause menopause phase

144

: 00:11:22

with that lower estrogen levels.

145

: 00:11:24

And then two, do you expect it to sort

of level out, like, like you said, it's

146

: 00:11:28

a drastic change when we go through

something like this where all of a sudden

147

: 00:11:31

our body's used to functioning at this

certain level and then it, it drops.

148

: 00:11:36

And so do you guys see this change?

149

: 00:11:38

And I don't even know if this is

possible to study, I guess long term

150

: 00:11:42

after menopause and once your body

starts to reregulate at that, that

151

: 00:11:47

new normal, is there sort of this

fluctuation and change longer term too?

152

: 00:11:53

Emily Hilz: So to address your

first question, when you say

153

: 00:11:57

starting it earlier, you probably

mean like estrogen replacement

154

: 00:12:00

Kelsy: Yes, exactly.

155

: 00:12:02

Emily Hilz: Yeah.

156

: 00:12:02

And i'm not a physician,

157

: 00:12:05

Kelsy: Yes.

158

: 00:12:06

Emily Hilz: am not making any

physician type recommendations.

159

: 00:12:10

But there is certainly a pretty

prevalent theory in the field called

160

: 00:12:16

the, lifetime estrogen Exposure theory

which posits that taking, hormonally

161

: 00:12:22

active drugs that are meant to be

hormonally active, not things that

162

: 00:12:26

are not meant to be hormonally active.

163

: 00:12:28

I'm sure we'll get into

that a little bit later.

164

: 00:12:31

Can actually improve your

long-term cognitive function.

165

: 00:12:35

So women who have taken birth control

pills for longer in their lives, or

166

: 00:12:40

women who start estrogen replacement

therapies earlier, consistently

167

: 00:12:44

perform better on a host of cognitive

tests and, report better outcomes.

168

: 00:12:50

In terms of when you should start,

that's definitely a conversation

169

: 00:12:54

to have with your physician.

170

: 00:12:56

And I, hopefully there's some, a

physician that's, versed in that field.

171

: 00:13:01

Somebody who really does have

expertise in women's health would

172

: 00:13:04

be who I would wanna talk to.

173

: 00:13:07

But, speaking anecdotally, I have a

friend who is 35 and she was talking to

174

: 00:13:15

her doctor, who's a really great doctor,

and she was talking about the brain fog

175

: 00:13:20

and exhaustion that she's been feeling.

176

: 00:13:22

And the doctor prescribed her a low

level vaginal estrogen cream, and she

177

: 00:13:28

has just been raving about how great

it's been and how helpful it's been.

178

: 00:13:32

So I think she's one of those

people who maybe has naturally lower

179

: 00:13:35

levels at an earlier point in life.

180

: 00:13:37

And, jury's out.

181

: 00:13:38

We're still in our thirties

right now, so we'll find out.

182

: 00:13:41

Hopefully it's gonna work

out really well for her.

183

: 00:13:44

It seems to be working well for her.

184

: 00:13:45

Now,

185

: 00:13:46

Kelsy: And then what about

part two, I guess, of these,

186

: 00:13:50

Emily Hilz: two,

187

: 00:13:50

Kelsy: Once your body re regulates on

this new level and gets used to that,

188

: 00:13:54

what effects do you guys see there?

189

: 00:13:56

Emily Hilz: I would say what we tend

to see when we over optimize a female

190

: 00:13:59

rat is that it starts responding

more similarly to a male rat.

191

: 00:14:05

So while I would say that it's gonna be

a change, it doesn't necessarily have to

192

: 00:14:10

be contextualized as maladaptive or bad.

193

: 00:14:16

It's just what is the new normal for you.

194

: 00:14:19

I am speaking, informally, in that

regard from a human perspective.

195

: 00:14:24

But from an animal perspective,

that is what we tend to see is like

196

: 00:14:28

when we measure female rats in low

hormone phases, or we over optimize

197

: 00:14:32

them, we tend to see them performing

at levels that males perform.

198

: 00:14:38

So a female could be up higher in terms of

their cognitive flexibility or motivation,

199

: 00:14:44

and then we over optimize them.

200

: 00:14:46

And then they are a little lower, but

they're not, below the male population,

201

: 00:14:51

they're just lower than they were when

they were in the high estrogen phases.

202

: 00:14:56

Kelsy: Comparatively, like before and

after for that same rat or individual.

203

: 00:15:01

Emily Hilz: That's hard to say because

usually we do it between groups.

204

: 00:15:04

Kelsy: Okay.

205

: 00:15:05

Emily Hilz: Yeah, I've never really done

that type of study where we looked at

206

: 00:15:08

before and after in the same animal.

207

: 00:15:11

Instead it would be like this group

of animals was high estrogen, this

208

: 00:15:14

group of animals was over optimiz.

209

: 00:15:15

And then we also had a group of males and

we compared cognitive and motivational

210

: 00:15:19

outcomes in those types of animals to see

how estrogen levels impact different types

211

: 00:15:26

of behavior in the realm of cognitive

attentional function and motivation.

212

: 00:15:31

Kelsy: You also, I know a lot of

your research focuses on hormonal

213

: 00:15:33

contraceptives specifically, and we

kind of skipped over that part, but I

214

: 00:15:36

definitely wanna cover that as well too.

215

: 00:15:38

So, what role do hormonal contraceptives

play specifically for like younger

216

: 00:15:44

women, twenties, thirties, those who

might be on a hormonal contraceptive?

217

: 00:15:48

What role do those play within our brains

as it relates to the dopamine system?

218

: 00:15:54

Emily Hilz: Yeah, I will, caveat,

I studied hormonal contraception in

219

: 00:15:58

graduate school, and then I've moved on

to studying endocrine disruptors now.

220

: 00:16:02

So it's not really an active research

line that I'm continuing to pursue, but

221

: 00:16:07

I do hope to come back to it because it

was something I was always working for.

222

: 00:16:11

It's so relevant for women.

223

: 00:16:13

It's so interesting.

224

: 00:16:15

but not very predominantly studied

in women's health research or just,

225

: 00:16:22

in neuroscience research aiming to

characterize the, female neuroscientific

226

: 00:16:29

perspective, which there's a big

movement which has been going on for

227

: 00:16:32

decades of, sex as a biological variable

and including females in biomedical

228

: 00:16:38

research to improve our standards and

drug manufacturing and recommendations.

229

: 00:16:45

And I'm going try not to get on a tangent

here, but I will say that initiative has

230

: 00:16:50

been in place at the NIH for decades.

231

: 00:16:53

And you still see tons of experiments

that are only done in males and

232

: 00:16:57

they'll say, oh, we didn't wanna use

females because they're variable,

233

: 00:17:01

because they have est extra cycles.

234

: 00:17:02

And it's that's not even always true.

235

: 00:17:05

And so that's an aside a

different conversation, but,

236

: 00:17:09

Kelsy: Hey, I'm in the same mindset.

237

: 00:17:11

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

of women's health work and I try and get

on a lot of researchers and scientists and

239

: 00:17:22

people who are willing to go through the

hard efforts and study women specifically.

240

: 00:17:27

So, and given all of our phases, right?

241

: 00:17:29

I mean, it's so hard to study

women in general anyways, because

242

: 00:17:33

of our menstrual cycles and the

variability within that pregnancy.

243

: 00:17:36

Who knows whether or not, I'm sure like

the people that you might be studying if

244

: 00:17:41

you are doing human studies, are maybe

going to get pregnant and then all of

245

: 00:17:44

a sudden there's a new variable that.

246

: 00:17:46

You might not have been able, like

you might not have thought to exclude

247

: 00:17:50

early on and then add in hormonal

contraceptives and things like that too.

248

: 00:17:53

So it's, it's complex and complicated

and we are complicated and complex, but

249

: 00:17:58

we deserve to, to be studied and to be

incorporated in studies in all of our,

250

: 00:18:02

many phases of our lives so that we can

have better knowledge of our bodies.

251

: 00:18:08

And then yeah, subsequent better

care from a variety of, of

252

: 00:18:11

healthcare providers and industries.

253

: 00:18:14

Emily Hilz: Yeah, I definitely have a lot

of thoughts about this specifically that

254

: 00:18:19

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

variation of hormones over the cycle.

256

: 00:18:25

So if you have an experimental

group, a lot of the reasons that

257

: 00:18:28

females get excluded from research

is because they're so variable, quote

258

: 00:18:33

unquote, because of their cycle.

259

: 00:18:36

But if you have a well powered

experiment, you could take these,

260

: 00:18:39

an animal experiment, let's say,

and you have enough animals in it,

261

: 00:18:43

then that creates an average, and

that would be your female average

262

: 00:18:46

from across all phases of the cycle.

263

: 00:18:47

So I think it's a cop out personally

in terms of, I think there's

264

: 00:18:52

nothing wrong with focusing on

one sex for a research question.

265

: 00:18:56

But I think if the only reason that

you're doing that is because you.

266

: 00:19:00

Don't want to with including the

other sex, then I don't think

267

: 00:19:03

that's a great reason to do it.

268

: 00:19:05

But we'll get back to hormonal

contraception cause that's what

269

: 00:19:08

we're talking about right now.

270

: 00:19:11

So you were asking me about motivation,

the dopamine system, contraceptives.

271

: 00:19:17

The thing with hormonal contraception

is that there's not a lot of preclinical

272

: 00:19:23

or even human epidemiological data

about its effects outside of, the

273

: 00:19:28

reproductive ones that it's used for.

274

: 00:19:31

And in the last, I would say maybe 10

years, realistically, like five years,

275

: 00:19:38

there've been a lot more researchers

studying hormonal contraception.

276

: 00:19:42

There's someone I know named Jesse

LACAs who is really spearheading

277

: 00:19:47

the neurobehavioral research in.

278

: 00:19:50

Hormonal contraceptive use, who's so

impressive and doing a bunch of stuff.

279

: 00:19:55

And we collaborated a little bit to

write a review of like how to study these

280

: 00:20:00

synthetic hormones in animal models.

281

: 00:20:03

But I wanted to study it specifically

because I was previously studying just

282

: 00:20:09

the general esra cycle phases and how

they contribute to how females learn.

283

: 00:20:15

And what I was studying was how the

female brain represents context.

284

: 00:20:21

So if you are of familiar with the

idea of let's say if you study in a

285

: 00:20:28

certain context like chew gum or you

study at the library, be able to recall

286

: 00:20:35

information better when you're tested on

it later if you're in that same context.

287

: 00:20:39

And that all happens in the hippocampus,

which is another region of the brain

288

: 00:20:42

that's very sensitive to estrogen.

289

: 00:20:45

And so I was interested to know how

estrogen levels across the cycle

290

: 00:20:49

impacted context representation.

291

: 00:20:52

And I found that female rats were

better at encoding context and

292

: 00:20:56

differentiating between context when

they were tested in high hormone

293

: 00:21:00

levels or when they learned in a high

hormone level and then were tested

294

: 00:21:03

in a different phase of their cycle.

295

: 00:21:05

So it was like the cycle was acting

as its own context basically, which

296

: 00:21:10

called this like an internal context.

297

: 00:21:11

It's oh, when I'm stressed out,

suddenly I, stress is an internal

298

: 00:21:15

state, those types of things.

299

: 00:21:17

And so I started thinking about

hormonal contraception as this

300

: 00:21:23

internal context that we put

ourselves in for long periods of time.

301

: 00:21:28

What happens when that context changes is

the perspective I was taking when I was

302

: 00:21:34

first studying hormonal contraception was

does it create its own internal context?

303

: 00:21:39

Does that help learn or encode

information or how do changes in it

304

: 00:21:44

help us learn or encode information?

305

: 00:21:46

so I think I would say it's a dual

perspective in my research of one,

306

: 00:21:51

how does modulating our hormone levels

synthetically impact the way that

307

: 00:21:55

we encode and recall information?

308

: 00:21:58

And then two, does that hormone state

that is exogenously being manipulated,

309

: 00:22:04

create an internal context and

then how does that also influence

310

: 00:22:07

the way that we learn and recall?

311

: 00:22:10

and I found a couple

of interesting things.

312

: 00:22:13

One thing that I found was that the

rats on hormones, so I was comparing

313

: 00:22:17

basically a low phase estrogen.

314

: 00:22:20

Cycle rat to a high phase rat and then a

contraceptive rat having them go through

315

: 00:22:26

some reward learning and memory tests.

316

: 00:22:29

And I found that the hormonal

contraception rat was performing pretty

317

: 00:22:34

much at the same level that the low

estrogen phase rat was performing.

318

: 00:22:38

And they were both lower

than the high phase rat.

319

: 00:22:41

And what I was testing

them for was a memory of an

320

: 00:22:44

amphetamine associated context.

321

: 00:22:46

So I was testing how much they

preferred the amphetamine, how well they

322

: 00:22:49

remembered the context, they learned

it in, how well they extinguished

323

: 00:22:53

their preference for the amphetamine.

324

: 00:22:55

And then I also looked at dopamine

cell numbers and activity in their

325

: 00:22:59

brains after the study was finished.

326

: 00:23:02

And so the contraceptive rats were

performing similar to the low hormone

327

: 00:23:08

rats in terms of they didn't prefer the

amphetamine as much, they still preferred

328

: 00:23:13

it because it's still a pretty stimulating

drug, but not as much as the rats that

329

: 00:23:18

were in the high estrogen phase, which

sort of suggests that reduction in hormone

330

: 00:23:22

levels was impacting their preference

and then they extinguished easier.

331

: 00:23:28

And then at the end of the study,

when I was looking at their dopamine

332

: 00:23:33

activity, they also had lower dopamine

activity levels compared to the

333

: 00:23:37

high estrogen rat, but they were

similar to the low estrogen rat.

334

: 00:23:41

And this is something that I think,

we got into before where thinking

335

: 00:23:45

about the context that we talk about

hormonal contraception, because.

336

: 00:23:49

my research experience, I haven't

found it to be harmful necessarily.

337

: 00:23:55

It's just, it's the same as getting used

to, perimenopause or something where

338

: 00:24:00

they're performing at the same level

as the rat and it's low estrogen phase.

339

: 00:24:03

They're not showing strong impairments.

340

: 00:24:06

They're just not as

the high estrogen base.

341

: 00:24:09

Kelsy: It's what you compare it to.

342

: 00:24:10

And I like how you said that.

343

: 00:24:11

'cause it's like, okay, positive versus

negative, you have to have a comparison

344

: 00:24:14

value anyways between, is this a positive

behavior due to it or is it a negative?

345

: 00:24:20

Well, we don't know unless we

have something to compare it to.

346

: 00:24:22

And I also like how you corrected me

as we were just kind of talking before

347

: 00:24:26

about how initially we can think of

hormonal contraceptives and their effect

348

: 00:24:31

on the dopamine system as maybe a.

349

: 00:24:34

You know, my words not

yours, negative thing.

350

: 00:24:37

And you had said, and correct me

saying, you know, it just depends on

351

: 00:24:41

the context that we talk about it in

where if we're talking about how we can

352

: 00:24:45

lower some of the pursuit or goal-driven

behaviors in someone who has more

353

: 00:24:51

maladaptive behaviors, like possibly

an addiction or things like that,

354

: 00:24:54

like that is a great context for that.

355

: 00:24:56

So I like how you, phrase different

things to let us know it's not a

356

: 00:25:01

good or bad thing, it's just how

our bodies are functioning in this

357

: 00:25:03

new state or in this new context.

358

: 00:25:06

Whether or not we are on hormonal

contraceptives or not, or whether we are

359

: 00:25:10

on estrogen replacement therapy or not.

360

: 00:25:12

Emily Hilz: Yeah.

361

: 00:25:12

I really had a great conversation with Dr.

362

: 00:25:16

Andrea Gore, who is my

mentor here at UT Austin.

363

: 00:25:20

When I was first joining her

lab, I was telling her, I kind

364

: 00:25:23

of wanna continue studying

hormonal contraception in the lab.

365

: 00:25:27

And she wasn't discouraging me from doing

it, but she did say something to me that

366

: 00:25:31

has stuck with me strongly ever since.

367

: 00:25:34

This is a politically

charged field in some ways.

368

: 00:25:38

And if you frame your research,

like a lot of people when they do

369

: 00:25:43

research, they here's the problem.

370

: 00:25:45

This is a problem, this is bad.

371

: 00:25:48

And we live in a climate where

there are parties who are interested

372

: 00:25:53

in skewing the things that you

say to say, okay, maybe if.

373

: 00:25:57

Hormonal contraception is so

bad that we shouldn't have it,

374

: 00:26:01

which is probably not great.

375

: 00:26:04

At least that's not the stance that I

take and then also talking, when you

376

: 00:26:08

were talking about substance use, like

that was actually a huge motivation

377

: 00:26:12

for me in studying it because I was

really interested in how contraceptives

378

: 00:26:17

would impact substance abuse treatment.

379

: 00:26:23

with the idea being that if you are

somebody who has like a substance use

380

: 00:26:27

disorder and maybe you are or are not

on hormonal contraception at the time

381

: 00:26:33

that you developed this disorder, how

would changes in your contraception

382

: 00:26:38

availability during treatment and then

later with your finished treatment

383

: 00:26:42

and go back into the world, how

might that impact your likelihood

384

: 00:26:46

of having a long-term successful

outcome with substance abuse disorder?

385

: 00:26:51

Thinking from the perspective that

maybe when you go for treatment, you

386

: 00:26:55

might not have it available anymore,

or maybe it becomes available and that

387

: 00:26:59

creates a new internal context for you

that changes your treatment outcomes.

388

: 00:27:03

And then if you go back out into the

world and whatever that availability

389

: 00:27:07

is, goes back to how it used to

be, that could even act as like

390

: 00:27:09

a internal trigger for relapse.

391

: 00:27:13

Kelsy: Totally.

392

: 00:27:13

And thinking of it not as like just

in the context of birth control, but

393

: 00:27:19

also it affects a lot of other systems

positively within our bodies too.

394

: 00:27:24

And I'm saying this now and I don't

have the research to back it up, but

395

: 00:27:28

I have been told that a decreased risk

of a certain type of cancer, and I'm

396

: 00:27:32

forgetting the type of cancer, but a

reproductive cancer and having hormonal

397

: 00:27:36

contraceptives earlier on can reduce

your risk for that kind of thing.

398

: 00:27:39

So just thinking of it, not always

in the context of what we are told,

399

: 00:27:45

I guess it's for, and thinking

of it, like you said, for other.

400

: 00:27:48

Ways to help people that are struggling

with other types of things, because

401

: 00:27:53

estrogen does affect a lot of systems

within our body, just like dopamine does.

402

: 00:27:57

And if dopamine and estrogen are

related, how can we use the two

403

: 00:28:00

to, to help people in other ways?

404

: 00:28:02

So I love that, that you

were looking into that.

405

: 00:28:05

Emily Hilz: Yeah, I would say my career

is defined by thinking about things

406

: 00:28:08

outside of the way that we were like.

407

: 00:28:11

Educated early on to think about them.

408

: 00:28:13

So I think of estrogen, not

as a reproductive hormone,

409

: 00:28:17

but as a neuromodulator.

410

: 00:28:18

And I think of it as an internal

context and I think of it, as

411

: 00:28:22

something that drives development,

or, thinking of hormonal contraception

412

: 00:28:26

outside of their efficacy for birth

control, but also in the brain really

413

: 00:28:30

and beyond in terms of behavior.

414

: 00:28:33

But yeah, that positive spin is,

I think part of the misconception

415

: 00:28:40

around birth control use.

416

: 00:28:42

I would say right now there's a big

conversation around endocrine disruptors.

417

: 00:28:47

And so I think the natural progression

of thought is, oh, if you take

418

: 00:28:51

something that impacts your hormone

levels, that has to be bad, right?

419

: 00:28:54

But endocrine disruptors

are not pharmaceutical.

420

: 00:28:56

They're not designed to do that.

421

: 00:28:58

And like you wouldn't take

hormonal contraception when

422

: 00:29:00

you're actively pregnant.

423

: 00:29:02

That would be a bad time to do it.

424

: 00:29:05

But women who take them I think

about 10% of women who take hormonal

425

: 00:29:09

contraception sort of mood disorders.

426

: 00:29:13

But also a very appreciable

number of women report improved

427

: 00:29:17

mood and various outcomes.

428

: 00:29:20

I'm gonna focus on mood 'cause that's

the one I've read the most about.

429

: 00:29:22

so they're certainly helpful for

people and that's all down to

430

: 00:29:25

individual differences and finding

right type of contraception for you.

431

: 00:29:29

And maybe there isn't one.

432

: 00:29:31

For some people it might

be better not to use it.

433

: 00:29:38

It's got a little bit of a hurdle to

use, but once it gets working, it works

434

: 00:29:42

great, I think, and it's just very.

435

: 00:29:45

No frill science forward I wasn't

trying to influence people's opinions.

436

: 00:29:50

I just wanted them to have

information when I made it.

437

: 00:29:53

So

438

: 00:29:54

Kelsy: You get that it reads that way.

439

: 00:29:56

And I will say, when you said, I forget

the words you used to describe it, but

440

: 00:30:01

not basically not the most tech forward

platform and like being, what did you say?

441

: 00:30:06

Like old two thousands old, you

know, two thousands based computer,

442

: 00:30:10

like it is a little bit nostalgic

and I actually really liked that.

443

: 00:30:13

So I liked using it that way.

444

: 00:30:15

I liked logging on and being

like, oh my gosh, wait, this

445

: 00:30:17

is so simple as a user to use.

446

: 00:30:20

So I loved it.