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:

endoscreen.org

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/

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

2

its involvement in motivation, reward,

pursuit, learning, behavior, and mood.

3

Emily Hilz: Yeah, great.

4

So the dopamine system is part of the

brain's reward and motivational system.

5

Dopamine neurons are primarily

located in the midbrain, which

6

is in the back of our brains.

7

And they send projections throughout

various regions of the brain,

8

including the nucleus, accumbens,

striatum, and the prefrontal cortex.

9

And dopamine does unique things

in different regions of the brain.

10

So in the nucleus accumbens, it's

involved in processing primary

11

rewards, and then that information is

integrated by our prefrontal cortex,

12

which is our executive control system

to make decisions about when and how

13

we seek rewards and exert control over

how intensely we seek those rewards.

14

It's a very integrated system that

impacts pretty much everything that we do.

15

Learning and memory and motivation.

16

Kelsy: One thing I have been

interested in is, of course, with

17

an audience of primarily women.

18

Are there any differences in how

the dopamine system affects the male

19

brain compared to the female brain?

20

Are there any sex differences

that you guys have seen?

21

Emily Hilz: I would say, in terms

of its basic function, it does work

22

the same way in males and females.

23

But an important, sex specific effect

about dopamine is that dopamine neurons

24

are very estrogen sensitive, which means

that when they're exposed to estrogens,

25

they fire a lot more rapidly, they release

more dopamine, that means that women are.

26

Kind of classically considered to be

more sensitive to rewarding stimuli

27

especially during phases of our cycle

where estrogens might be higher or,

28

we're taking estrogen replacement

therapies or something like that.

29

So we do see, more reward seeking

behavior in females compared to males.

30

Kelsy: That's interesting because one

of the things that caused me to search

31

out someone like you who's researching

this kind of thing and looking into

32

hormonal effects on our dopamine

system, was my own experience, I guess

33

with my own body and my own tracking

and just noticing, especially in that

34

like early phase of my cycle, after

my period was over, I noticed, okay,

35

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

36

I'm back at it.

37

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

motivated, way more disciplined, way more.

38

goal driven in that phase and I started

realizing, I was like, oh, hang on.

39

This is kind of happening cyclically.

40

So you mentioned a little bit how

estrogen and dopamine go hand in hand.

41

Explain a little bit more about

that, especially in regards to

42

like the menstrual cycle and how

different high hormone phases and

43

low hormone phases affect our ability

to be more goal-driven or be more

44

motivated or be more disciplined.

45

Emily Hilz: Sure.

46

So I study these things using rats.

47

And in rats have what is

called an est extra cycle.

48

It's very similar conceptually

to the human menstrual cycle.

49

And the main difference basically

is that rats don't menstruate.

50

They reabsorb their, you're lining up each

cycle and it only lasts four or five days,

51

which is great for a research context

because then you can study things in four

52

or five days instead of over months and

53

Kelsy: Right,

54

Emily Hilz: But things that are

pretty well accepted, I would say at

55

this point in science is that the.

56

Estro cycle influences how much females

will seek out rewarding stimuli.

57

So a rat that is in a high estrogen

phase of its cycle will drink a lot more

58

alcohol, or it will emit like pleasure

calls more rapidly and intensely in

59

response to what we would call like

dopaminergic or stimulant drugs.

60

That's what researchers use.

61

When we study reward, we use rewarding

stimuli, and the most rewarding

62

stimuli tend to be dopaminergic

drugs like amphetamine or cocaine.

63

and extra cycle will impact the

way that females will seek out.

64

Those rewards, how much

they will consume them.

65

when we talk about motivation, I think

there's sort of two types of motivation.

66

It would be essentially motivation

in maybe a positive context or

67

motivation, which could be maladaptive

compulsive rewards seeking.

68

Higher estrogen phases could be associated

with compulsive behaviors, depending

69

on a lot of factors going into that.

70

Kelsy: When we talk about being more

motivated or less motivated, or more

71

disciplined or less disciplined,

does any of that have to do with how

72

much more dopamine is released like

a delta between our baseline and our

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peak, or our baseline and our valley?

74

Like if we are someone who has.

75

I guess more estrogen in one of the

different phases of our cycle, does that

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necessarily equate to, I guess, more

dopamine released and more motivation?

77

Or where our baseline is, does that go

into play where if I am a naturally,

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like if my dopamine levels are naturally

a little higher and I happen to, you

79

know, have maybe a little bit more

estrogen in a certain phase with that,

80

like I guess the delta between the

two, does that play into it at all?

81

Emily Hilz: I'm not very familiar with

that kind of level of resolution, but I

82

think it's interesting that you bring up

the idea of sort of natural differences

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between people because there's a huge

amount of difference between individuals

84

in terms of how much estrogen we release.

85

Or, the activity of our dopamine systems.

86

That's why, some people have

a DHD and some people don't.

87

Not for estrogen, but for, dopamine

and other neuromodulators like that.

88

And I think that could go back

to early life development.

89

So maybe you are some body who has

been, through whatever reason, maybe,

90

just that's something that has emerged

along your genetic line or maybe, in

91

terms of endocrine disruptor exposure.

92

But either way, maybe you're somebody

who has higher estrogen levels or during

93

early life when the brain is developing.

94

That could certainly lead to, more, I

guess I'll go with activity or sensitivity

95

in the dopamine system, and that could

certainly impact the way that you.

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Experience the world across a huge

domain of areas, be it the way that

97

you learn how much, how easy it is for

you to pay attention to things, the

98

motivation that you feel your sensitivity

to, rewarding stimuli and how well you

99

can we call this top, top-down control.

100

So the prefrontal cortex exerts

top-down control over the striatal

101

tissues to stop you from engaging in

maladaptive reward seeking behaviors

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that could be like overeating or

drug abuse or anything like that.

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Or, and then the alternative to that

is bottom up control, where it's

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like the dopamine system is taking

control from the prefrontal cortex.

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And that's when you start getting

into compulsive behaviors.

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And, know, motivation in that

context would be compulsive.

107

Kelsy: So flipping gears a little

bit to from the menstrual cycle to

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something like menopause, I know

I told you I selfishly want more

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people to start thinking about that.

110

And I know our hormones

change in that period.

111

And I know this might not directly

correlate with your research, but

112

what would you say for when we as

women experience or go through the

113

phase of menopause, how might you

expect that to alter how our brains

114

and our dopamine systems function?

115

Emily Hilz: That's a great question.

116

Again, based on research that

has been performed in rodents,

117

rats don't go through menopause.

118

And so we use ectomy

models to model menopause.

119

This isn't research that I've done

myself, but I'm pretty familiar

120

with it because that's how we study.

121

When there are hormones and when there

aren't hormones, in regard to reward,

122

generally what you see an overpromised

rat, and this is like pretty well

123

corroborated in human data, is that

removal of endogenous estrogens.

124

Either via ectomy in a model or in human

women impairs reward signaling processes.

125

You'll see less motivation for reward.

126

You'll also see a lot

less behavior in general.

127

And then moving out of the

basic reward system into more

128

complex cognitive behavior.

129

A lot of women, report brain fog

during, menopause perimenopause period.

130

And that's.

131

Pretty well established to be due

to reduced estrogen availability.

132

You have this hormone that is

very synaptically exciting.

133

What it does is it stimulates a lot

of activity in the brain, not just

134

in the dopamine system, but across

a lot of different types of neurons.

135

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

huge change to go through cognitively.

136

And so I can't even think of, an

example that it wouldn't affect.

137

Kelsy: Yeah, totally.

138

I know you also mentioned that possibly

starting it earlier might offset

139

some of the maybe less desirable

impacts of this lower estrogen phase

140

in our life a little bit or so.

141

I guess question one is their benefit to.

142

Maybe not like waiting it out and letting

my body sort of try and regulate it

143

when it comes to how our body functions

in that perimenopause menopause phase

144

with that lower estrogen levels.

145

And then two, do you expect it to sort

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

146

a drastic change when we go through

something like this where all of a sudden

147

our body's used to functioning at this

certain level and then it, it drops.

148

And so do you guys see this change?

149

And I don't even know if this is

possible to study, I guess long term

150

after menopause and once your body

starts to reregulate at that, that

151

new normal, is there sort of this

fluctuation and change longer term too?

152

Emily Hilz: So to address your

first question, when you say

153

starting it earlier, you probably

mean like estrogen replacement

154

Kelsy: Yes, exactly.

155

Emily Hilz: Yeah.

156

And i'm not a physician,

157

Kelsy: Yes.

158

Emily Hilz: am not making any

physician type recommendations.

159

But there is certainly a pretty

prevalent theory in the field called

160

the, lifetime estrogen Exposure theory

which posits that taking, hormonally

161

active drugs that are meant to be

hormonally active, not things that

162

are not meant to be hormonally active.

163

I'm sure we'll get into

that a little bit later.

164

Can actually improve your

long-term cognitive function.

165

So women who have taken birth control

pills for longer in their lives, or

166

women who start estrogen replacement

therapies earlier, consistently

167

perform better on a host of cognitive

tests and, report better outcomes.

168

In terms of when you should start,

that's definitely a conversation

169

to have with your physician.

170

And I, hopefully there's some, a

physician that's, versed in that field.

171

Somebody who really does have

expertise in women's health would

172

be who I would wanna talk to.

173

But, speaking anecdotally, I have a

friend who is 35 and she was talking to

174

her doctor, who's a really great doctor,

and she was talking about the brain fog

175

and exhaustion that she's been feeling.

176

And the doctor prescribed her a low

level vaginal estrogen cream, and she

177

has just been raving about how great

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

178

So I think she's one of those

people who maybe has naturally lower

179

levels at an earlier point in life.

180

And, jury's out.

181

We're still in our thirties

right now, so we'll find out.

182

Hopefully it's gonna work

out really well for her.

183

It seems to be working well for her.

184

Now,

185

Kelsy: And then what about

part two, I guess, of these,

186

Emily Hilz: two,

187

Kelsy: Once your body re regulates on

this new level and gets used to that,

188

what effects do you guys see there?

189

Emily Hilz: I would say what we tend

to see when we over optimize a female

190

rat is that it starts responding

more similarly to a male rat.

191

So while I would say that it's gonna be

a change, it doesn't necessarily have to

192

be contextualized as maladaptive or bad.

193

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

194

I am speaking, informally, in that

regard from a human perspective.

195

But from an animal perspective,

that is what we tend to see is like

196

when we measure female rats in low

hormone phases, or we over optimize

197

them, we tend to see them performing

at levels that males perform.

198

So a female could be up higher in terms of

their cognitive flexibility or motivation,

199

and then we over optimize them.

200

And then they are a little lower, but

they're not, below the male population,

201

they're just lower than they were when

they were in the high estrogen phases.

202

Kelsy: Comparatively, like before and

after for that same rat or individual.

203

Emily Hilz: That's hard to say because

usually we do it between groups.

204

Kelsy: Okay.

205

Emily Hilz: Yeah, I've never really done

that type of study where we looked at

206

before and after in the same animal.

207

Instead it would be like this group

of animals was high estrogen, this

208

group of animals was over optimiz.

209

And then we also had a group of males and

we compared cognitive and motivational

210

outcomes in those types of animals to see

how estrogen levels impact different types

211

of behavior in the realm of cognitive

attentional function and motivation.

212

Kelsy: You also, I know a lot of

your research focuses on hormonal

213

contraceptives specifically, and we

kind of skipped over that part, but I

214

definitely wanna cover that as well too.

215

So, what role do hormonal contraceptives

play specifically for like younger

216

women, twenties, thirties, those who

might be on a hormonal contraceptive?

217

What role do those play within our brains

as it relates to the dopamine system?

218

Emily Hilz: Yeah, I will, caveat,

I studied hormonal contraception in

219

graduate school, and then I've moved on

to studying endocrine disruptors now.

220

So it's not really an active research

line that I'm continuing to pursue, but

221

I do hope to come back to it because it

was something I was always working for.

222

It's so relevant for women.

223

It's so interesting.

224

but not very predominantly studied

in women's health research or just,

225

in neuroscience research aiming to

characterize the, female neuroscientific

226

perspective, which there's a big

movement which has been going on for

227

decades of, sex as a biological variable

and including females in biomedical

228

research to improve our standards and

drug manufacturing and recommendations.

229

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

here, but I will say that initiative has

230

been in place at the NIH for decades.

231

And you still see tons of experiments

that are only done in males and

232

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

females because they're variable,

233

because they have est extra cycles.

234

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

235

And so that's an aside a

different conversation, but,

236

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

237

I do a lot of just education in general,

and I'm a women's health pt, so I do a lot

238

of women's health work and I try and get

on a lot of researchers and scientists and

239

people who are willing to go through the

hard efforts and study women specifically.

240

So, and given all of our phases, right?

241

I mean, it's so hard to study

women in general anyways, because

242

of our menstrual cycles and the

variability within that pregnancy.

243

Who knows whether or not, I'm sure like

the people that you might be studying if

244

you are doing human studies, are maybe

going to get pregnant and then all of

245

a sudden there's a new variable that.

246

You might not have been able, like

you might not have thought to exclude

247

early on and then add in hormonal

contraceptives and things like that too.

248

So it's, it's complex and complicated

and we are complicated and complex, but

249

we deserve to, to be studied and to be

incorporated in studies in all of our,

250

many phases of our lives so that we can

have better knowledge of our bodies.

251

And then yeah, subsequent better

care from a variety of, of

252

healthcare providers and industries.

253

Emily Hilz: Yeah, I definitely have a lot

of thoughts about this specifically that

254

I won't go into too much, but I'll say,

a part of the thing is like you have the

255

variation of hormones over the cycle.

256

So if you have an experimental

group, a lot of the reasons that

257

females get excluded from research

is because they're so variable, quote

258

unquote, because of their cycle.

259

But if you have a well powered

experiment, you could take these,

260

an animal experiment, let's say,

and you have enough animals in it,

261

then that creates an average, and

that would be your female average

262

from across all phases of the cycle.

263

So I think it's a cop out personally

in terms of, I think there's

264

nothing wrong with focusing on

one sex for a research question.

265

But I think if the only reason that

you're doing that is because you.

266

Don't want to with including the

other sex, then I don't think

267

that's a great reason to do it.

268

But we'll get back to hormonal

contraception cause that's what

269

we're talking about right now.

270

So you were asking me about motivation,

the dopamine system, contraceptives.

271

The thing with hormonal contraception

is that there's not a lot of preclinical

272

or even human epidemiological data

about its effects outside of, the

273

reproductive ones that it's used for.

274

And in the last, I would say maybe 10

years, realistically, like five years,

275

there've been a lot more researchers

studying hormonal contraception.

276

There's someone I know named Jesse

LACAs who is really spearheading

277

the neurobehavioral research in.

278

Hormonal contraceptive use, who's so

impressive and doing a bunch of stuff.

279

And we collaborated a little bit to

write a review of like how to study these

280

synthetic hormones in animal models.

281

But I wanted to study it specifically

because I was previously studying just

282

the general esra cycle phases and how

they contribute to how females learn.

283

And what I was studying was how the

female brain represents context.

284

So if you are of familiar with the

idea of let's say if you study in a

285

certain context like chew gum or you

study at the library, be able to recall

286

information better when you're tested on

it later if you're in that same context.

287

And that all happens in the hippocampus,

which is another region of the brain

288

that's very sensitive to estrogen.

289

And so I was interested to know how

estrogen levels across the cycle

290

impacted context representation.

291

And I found that female rats were

better at encoding context and

292

differentiating between context when

they were tested in high hormone

293

levels or when they learned in a high

hormone level and then were tested

294

in a different phase of their cycle.

295

So it was like the cycle was acting

as its own context basically, which

296

called this like an internal context.

297

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

suddenly I, stress is an internal

298

state, those types of things.

299

And so I started thinking about

hormonal contraception as this

300

internal context that we put

ourselves in for long periods of time.

301

What happens when that context changes is

the perspective I was taking when I was

302

first studying hormonal contraception was

does it create its own internal context?

303

Does that help learn or encode

information or how do changes in it

304

help us learn or encode information?

305

so I think I would say it's a dual

perspective in my research of one,

306

how does modulating our hormone levels

synthetically impact the way that

307

we encode and recall information?

308

And then two, does that hormone state

that is exogenously being manipulated,

309

create an internal context and

then how does that also influence

310

the way that we learn and recall?

311

and I found a couple

of interesting things.

312

One thing that I found was that the

rats on hormones, so I was comparing

313

basically a low phase estrogen.

314

Cycle rat to a high phase rat and then a

contraceptive rat having them go through

315

some reward learning and memory tests.

316

And I found that the hormonal

contraception rat was performing pretty

317

much at the same level that the low

estrogen phase rat was performing.

318

And they were both lower

than the high phase rat.

319

And what I was testing

them for was a memory of an

320

amphetamine associated context.

321

So I was testing how much they

preferred the amphetamine, how well they

322

remembered the context, they learned

it in, how well they extinguished

323

their preference for the amphetamine.

324

And then I also looked at dopamine

cell numbers and activity in their

325

brains after the study was finished.

326

And so the contraceptive rats were

performing similar to the low hormone

327

rats in terms of they didn't prefer the

amphetamine as much, they still preferred

328

it because it's still a pretty stimulating

drug, but not as much as the rats that

329

were in the high estrogen phase, which

sort of suggests that reduction in hormone

330

levels was impacting their preference

and then they extinguished easier.

331

And then at the end of the study,

when I was looking at their dopamine

332

activity, they also had lower dopamine

activity levels compared to the

333

high estrogen rat, but they were

similar to the low estrogen rat.

334

And this is something that I think,

we got into before where thinking

335

about the context that we talk about

hormonal contraception, because.

336

my research experience, I haven't

found it to be harmful necessarily.

337

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

to, perimenopause or something where

338

they're performing at the same level

as the rat and it's low estrogen phase.

339

They're not showing strong impairments.

340

They're just not as

the high estrogen base.

341

Kelsy: It's what you compare it to.

342

And I like how you said that.

343

'cause it's like, okay, positive versus

negative, you have to have a comparison

344

value anyways between, is this a positive

behavior due to it or is it a negative?

345

Well, we don't know unless we

have something to compare it to.

346

And I also like how you corrected me

as we were just kind of talking before

347

about how initially we can think of

hormonal contraceptives and their effect

348

on the dopamine system as maybe a.

349

You know, my words not

yours, negative thing.

350

And you had said, and correct me

saying, you know, it just depends on

351

the context that we talk about it in

where if we're talking about how we can

352

lower some of the pursuit or goal-driven

behaviors in someone who has more

353

maladaptive behaviors, like possibly

an addiction or things like that,

354

like that is a great context for that.

355

So I like how you, phrase different

things to let us know it's not a

356

good or bad thing, it's just how

our bodies are functioning in this

357

new state or in this new context.

358

Whether or not we are on hormonal

contraceptives or not, or whether we are

359

on estrogen replacement therapy or not.

360

Emily Hilz: Yeah.

361

I really had a great conversation with Dr.

362

Andrea Gore, who is my

mentor here at UT Austin.

363

When I was first joining her

lab, I was telling her, I kind

364

of wanna continue studying

hormonal contraception in the lab.

365

And she wasn't discouraging me from doing

it, but she did say something to me that

366

has stuck with me strongly ever since.

367

This is a politically

charged field in some ways.

368

And if you frame your research,

like a lot of people when they do

369

research, they here's the problem.

370

This is a problem, this is bad.

371

And we live in a climate where

there are parties who are interested

372

in skewing the things that you

say to say, okay, maybe if.

373

Hormonal contraception is so

bad that we shouldn't have it,

374

which is probably not great.

375

At least that's not the stance that I

take and then also talking, when you

376

were talking about substance use, like

that was actually a huge motivation

377

for me in studying it because I was

really interested in how contraceptives

378

would impact substance abuse treatment.

379

with the idea being that if you are

somebody who has like a substance use

380

disorder and maybe you are or are not

on hormonal contraception at the time

381

that you developed this disorder, how

would changes in your contraception

382

availability during treatment and then

later with your finished treatment

383

and go back into the world, how

might that impact your likelihood

384

of having a long-term successful

outcome with substance abuse disorder?

385

Thinking from the perspective that

maybe when you go for treatment, you

386

might not have it available anymore,

or maybe it becomes available and that

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creates a new internal context for you

that changes your treatment outcomes.

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And then if you go back out into the

world and whatever that availability

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is, goes back to how it used to

be, that could even act as like

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a internal trigger for relapse.

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Kelsy: Totally.

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And thinking of it not as like just

in the context of birth control, but

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also it affects a lot of other systems

positively within our bodies too.

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

have the research to back it up, but

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I have been told that a decreased risk

of a certain type of cancer, and I'm

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forgetting the type of cancer, but a

reproductive cancer and having hormonal

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contraceptives earlier on can reduce

your risk for that kind of thing.

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So just thinking of it, not always

in the context of what we are told,

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I guess it's for, and thinking

of it, like you said, for other.

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Ways to help people that are struggling

with other types of things, because

401

estrogen does affect a lot of systems

within our body, just like dopamine does.

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And if dopamine and estrogen are

related, how can we use the two

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to, to help people in other ways?

404

So I love that, that you

were looking into that.

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Emily Hilz: Yeah, I would say my career

is defined by thinking about things

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outside of the way that we were like.

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Educated early on to think about them.

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So I think of estrogen, not

as a reproductive hormone,

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but as a neuromodulator.

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And I think of it as an internal

context and I think of it, as

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something that drives development,

or, thinking of hormonal contraception

412

outside of their efficacy for birth

control, but also in the brain really

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and beyond in terms of behavior.

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But yeah, that positive spin is,

I think part of the misconception

415

around birth control use.

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I would say right now there's a big

conversation around endocrine disruptors.

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And so I think the natural progression

of thought is, oh, if you take

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something that impacts your hormone

levels, that has to be bad, right?

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But endocrine disruptors

are not pharmaceutical.

420

They're not designed to do that.

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And like you wouldn't take

hormonal contraception when

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you're actively pregnant.

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That would be a bad time to do it.

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But women who take them I think

about 10% of women who take hormonal

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contraception sort of mood disorders.

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But also a very appreciable

number of women report improved

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mood and various outcomes.

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

the one I've read the most about.

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so they're certainly helpful for

people and that's all down to

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individual differences and finding

right type of contraception for you.

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And maybe there isn't one.

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For some people it might

be better not to use it.

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It's got a little bit of a hurdle to

use, but once it gets working, it works

434

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

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No frill science forward I wasn't

trying to influence people's opinions.

436

I just wanted them to have

information when I made it.

437

So

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Kelsy: You get that it reads that way.

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And I will say, when you said, I forget

the words you used to describe it, but

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not basically not the most tech forward

platform and like being, what did you say?

441

Like old two thousands old, you

know, two thousands based computer,

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like it is a little bit nostalgic

and I actually really liked that.

443

So I liked using it that way.

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I liked logging on and being

like, oh my gosh, wait, this

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is so simple as a user to use.

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So I loved it.