Hormones, Drugs, and Pregnancy

Marsha Timmerman, LaSalle UniversityTracy Schatteman, Lincoln Land Community College

Gretchen A. Koch, Goucher CollegeAnton Weisstein, Truman State University

Goals

• Create a problem based learning module to teach students about hormones

• Three venues– Human A&P course: Reproductive system– Cell biology course: Cell signaling– Pharmacology course: Pharmacokinetics

Learning Objectives:Anatomy and Physiology

• Role of hormones in modulating female reproductive cycle

• Complexity of negative feedback mechanisms at the organismal level

• Pharmacology – intake, half-life, and excretion of medications

• Understand the public health implications of pregnancy and birth control

Learning Objectives:Cell Biology

• Structure and form of steroid molecules• Role/function of steroid hormones on

cellular level• Specificity of cells – what makes a cell a

target cell• Cell signaling receptors• Specificity of receptors – triggers and

outcomes• Applications to cancer on the cellular level

Problem Based Learning Concept Map

The Hook: Initial case history of woman who gets pregnant on birth control pills

Inquiry phase: students discuss and research into reproductive system, hormones and birth control pills. Students present what they have learned to the class.

Case history part 2: Provides more information

Investigative phase: students use tools such as Excel modules and AgentSheets to delve deeper into the subject. In this phase, each venue can move in the direction appropriate for the intent of their class.

Anatomy and Physiology ModuleInitial Case

Bill walks into the student lounge and sees Amy sitting in a corner looking very dejected. Bill approaches Amy.

Bill: “Hi Amy. You look upset. Is anything wrong?”Amy: “I guess. This morning I took a home pregnancy

test, and it came up positive. I’m really shocked that I’m pregnant. I need to think about it for a while.”

Bill: “Congratulations! I know that you and Ron have been talking about having a family. I did not realize that you had stopped using birth control.”

Amy: “That’s the problem. I am still taking birth control pills; I think the one I am on is called Aygestin. Ron and I were thinking about a family but were not quite ready to take the plunge. I guess we don’t need to make the decision any longer.”

Anatomy and Physiology ModuleStep 2

• Anticipated inquiries from initial student discussions– Can someone taking birth control get

pregnant?– How does the reproductive system work?– How does birth control work?– What are hormones?– What is Aygestin?

• Students should work on their own to obtain answers to the above questions.

• Students need to present what they have learned to their group.

Anatomy and Physiology ModuleStep 3

More of the case…

Amy goes to her doctor for a prenatal checkup.Amy: “I was taking my birth control pills as prescribed.

The only time I missed one was a couple of weeks ago when I was up very late studying for an exam. After exams, Ron and I went away for a weekend get away to enjoy ourselves before the summer semester started.”

Doctor: “Aygestin is a progesterone birth control pill. A woman’s reproductive system is controlled by a number of hormones that continually cycle.”

Female Reproductive Cycle

Feedback Mechanisms: Female Reproductive Hormones

http://www.vrp.com/graphics/fem_repro_homeo.jpg

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Assumptions of the Reproductive Hormone Model

• Average 28 day menstrual cycle

• Does not include: GnRH, LH, estrogen

• Birth control pills:– Progesterone only

(mini-pill) – Taken on days 1-21– Placebo days 22-28

• Progesterone – Suppresses FSH

levels– Small release in

follicular phase– Large release in luteal

phase – Day 26: levels decline

sharply• Pregnancy blocks

progesterone decline.

Pharmacokinetics• Study of how drugs move through the

body (1)• Enter via ingestion, injection,

absorption (1)• Exit via excretion, metabolism (1)• Possible Lesson: Birth control and

hormones– How many doses can one skip before you

get pregnant?– Must it correspond to the hormonal cycle?

A little mathematics…

• f(t): the dosage function (2)• Half-life rates: α and b• g(t): concentration of drug in GI tract• b(t): concentration of drug in bloodstream

GI Tract BloodIngestion

Decay in GI tract and

absorption into blood

Metabolism

( )f t ( )g t ( )b tb

Mathematical Equations

( ) ( )

( ) ( )

dg f t g tdtdb g t b tdt

b

b

Rate of change = Rate In – Rate Out The rate of change in the concentration of the drug in the GI tract is

equal to the amount being ingested minus the concentration that is decaying.

The rate of change in the concentration of the drug in the blood is equal to the concentration that is decaying from the GI tract minus the concentration decaying in the blood.

One Compartment Model

Ingestion

( )f tBlood

Metabolism

( )b t

• f(t): the dosage function (2)• Half-life rate: α• b(t): concentration of drug in bloodstream

Mathematical Equations

dbdt

f (t) b(t)

Rate of change = Rate In – Rate Out The rate of change in the concentration of the drug in the blood is

equal to the amount being ingested minus the concentration that is being metabolized.

Sliders to change

dosage functiondynamically.

User entry of drug

half-lives

Model descriptionand assumptions

Blood concentration versus GI concentration

Time is still independent variable.

Dosing Function Drug ConcentrationsVersus time

Comparisons of Steroids

Cholesterol Progesterone

TestosteroneEstrogen

Future directions

• Elaborate and improve Hormone Module• Public health applications

– GapMinder, CDC Website• Pharmacokinetics Modules

– Documentation, Case Study, Sample Labs• Model for cell signaling mechanisms

– AgentSheets

Acknowledgements

Tony Weisstein John JungckRaina RobevaMichael Garman, Sean Lonsdale, David Ludgin, Kelley Moran, and Katrina Ramirez-MeyerPrevious BioQUEST Participants

References1. Aygestin® Product Insert, Duramed Pharm., Inc., Pomona, NY, July 20072. Drugs@FDA, http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ 3. Conneely, O. and B. Jericevic. Progesterone Regulation of Reproductive Function

Through Functionally Distinct Progesterone Receptor Isoforms. Rev. in Endocrine & Metabolic Disorders 3:201, 2002

4. Menstrual cycle hormone animation, IAMSE http://www.healcentral.org/content/collections/McGill/MENSESANIMFINAL800x600.swf

5. Physician Information for Depo-Provera Pharmacia & Upjohn Company, Kalamazoo, MI, Feb. 2004

6. Shughrue, P., D. Lubahn, A. Negro-Vilar, K. Korach, and I. Merchenthaler. Responses in the brain of estrogen receptor a-disrupted mice. PNAS, 94:11008, 1997

7. Spitznagel, E. (Fall 1992) Two-Compartment Pharmacokinetic Models C-ODE-E. Harvey Mudd College, Claremont, CA.

8. Wierman, M. Sex steroid effects at target tissues: mechanisms of action, Advan. Physiol. Edu. 31: 26-33, 2007

9. Wierman, M. http://www.the-aps.org/education/refresher/Wierman%20talk/player.html

10. Yeargers, E.K., Shonkwiler, R.W., and Herod, J.V. (1996) An Introduction to the Mathematics of Biology. Birkhäuser.