Hormonal Drugs Flashcards

Question

Adverse effects of AAS

Answer 1

Selective Androgen Receptor Modulators (SARMs): androgen receptor agonists but are not steroids stimulate muscle growth developed to treat muscle wasting and osteoporosis of ageing None have been approved for medical use but they’ve been hijacked for their androgenic effects found in ‘dietary supplements’ athletes - Shayna Jack in 2019, GB 4x100m relay Tokyo

Answer 2

1. To describe how the human reproductive cycle works, including the function of pre -Pill contraceptive interventions. 2. To identify key individuals and events in the development of an effective hormonal -based form of contraception. 3. To identify issues around the FDA approval and post -marketing impact of the Pill to the present day. 4. To describe new directions in hormonal contraceptive development.

Answer 3

 Penis into vagina – with or without male orgasm.  Any live sperm can reach a viable egg if the woman is ovulating.  Fertilisation can take place within minutes -> up to five days later.  Sperm can live up to five days in the uterus and fallopian tubes.

Answer 4

 Reproduction is a major drive in any species.  Dimorphic sexual intercourse is the normal means by which the human species reproduces.  Timing of intercourse is not determined by oestrus cycle (as in animals): choices.  Sexual intercourse is specifically designed to produce new human beings.  This is why no form of contraception is 100% effective.  This is why there should be no such thing as a surprise pregnancy!

Answer 5

 Most ancient cultures believed that men and women both contributed to baby-making.  However, only women were believed to be infertile – like a field or a tree.  Most ancient cultures were desperate to have more children to maintain and increase their populations.  High infant mortality, early mortality, death in childbirth, risk of invasion.  Cultures with sick or disabled children exposed them at birth or sacrificed them.  Contraceptive attempts very often found in records relating to prostitution.

Answer 6

Barrier methods: vaginal suppositories - inserted plugs of gum or fibre.  Breast-feeding: suppresses ovulation.  Coitus interruptus/withdrawal = fewer sperm present.  Douching = highly risky; can push sperm further into the uterus.  Abstinence = 100% effective. Fallback:  Use of abortifacients and infanticide.

Answer 7

 Not all unplanned pregnancies are unwanted!  When and why is a pregnancy unwanted?  Physical reasons:  Women: 9 months, discomfort, painful birth, need to provide for child afterwards.  Cultural/social reasons: Women: shame, embarrassment, child is not the putative father’s, public humiliation, financial inconvenience, evidence of infidelity, possible death sentence in some cultures. Men: financial obligation to raise child; child is not putative father’s, evidence of infidelity

Answer 8

 First used as early as 15th century?  Used primarily to prevent transmission of STDs such as syphilis.  Made from linen, animal intestines or bladder, thin leather.  First rubber condom produced mid19th century.  Latex used 1930s onwards. Fallback: Use of abortifacients and infanticide.

Answer 9

 Ancient and medieval world:  Herbal preparations which would induce uterine cramping and expel a pregnancy.  Traditional herbs included rue, pennyroyal, ergot, nutmeg.  Use of alcohol to kill foetus.  Hot baths, jumping, falls.  Induced abortions using sharp objects.  Not always considered immoral if the pregnancy had not ‘quickened’ = mother had not felt child moving

Answer 10

Industrialisation - rubber, latex.  Popular press and advertising.  Cervical caps, vaginal sponges, primitive intra-uterine devices (IUDs), diaphragms, douching.  Use of elaborate language in advertising to conceal effects: ‘menstrual regulation’, ‘hygiene’.  1873: US Comstock Law declared contraception to be both obscene and illegal.  1803: Britain first passed anti-abortion laws, which then became stricter throughout the century

Answer 11

Early feminist thinkers opposed contraception and abortion as ‘male solutions’.  Argued that they damaged women, destroyed children, but liberated men from financial and moral responsibility.  Asked: what is so wrong with pregnancy?  Identified male domination/fear as factor that led women to seek dangerous illegal abortions.  Female power seen as linked to motherhood and family.  Envisioned a radical future where any woman could welcome any child in safety and comfort.

Answer 12

Dr Marie Stopes (1880-1958)  Palaeobotanist  1919: A Letter to Working Mothers on how to have healthy children and avoid weakening pregnancies.  1921: first Mothers’ Clinic opened in London – provided contraceptive advice.  Stopes did not support abortion.

Answer 13

 Katherine McCormick (1875- 1967) - husband developed schizophrenia.  Decided not to have any children because of fears of heritable disease.  Upon husband’s death, McCormick inherited around US$15 million.  Financed early Pill research.

Answer 14

Margaret Sanger (1879-1966) – mother died after 11 children  "I associated poverty, toil, unemployment, drunkenness, cruelty, quarreling, fighting, debts, jails with large families."  Published Birth Control Review.  founded the American Birth Control League in 1921.  Later known as Planned Parenthood.

Answer 15

The 'Pro Race' diaphragm/cervical cap - designed by Marie Stopes and manufactured and sold in London at her Mothers' Clinic.

Answer 16

Margaret Sanger and Marie Stopes were both eugenicists  Both targeted working-class women - ‘too fertile’.  Other pro-contraception pioneers such as Havelock Ellis (sexologist) criticised Stopes’ anti-Semitism.  Today: contraceptive rollout in developing countries still raises Issues of class, race, medical imperialism, neo-colonialism.  2020: Margaret Sanger’s name removed from Manhattan Planned Parenthood clinic  https://time.com/5869743/planned-parenthood-margaretsanger/

Answer 17

 Calendar-based methods had long history but were unreliable.  little accurate physiological knowledge of women’s bodies.  1905: Dutch physician Dr Theodore van der Velde = women ovulate once per cycle.  1920s: Ogino and Knaus pinpointed ovulation as most commonly occurring 14 days before next menstrual period.  1930: Drs John Smulders, Knaus and Ogino developed first calendarbased method of birth control.

Answer 18

 US doctor and researcher Gregory Pincus (1903- 1967)  Began studying hormonal biology and steroidal hormones  1934: produced successful in-vitro fertilization in rabbits  1951: Margaret Sanger approached Pincus to undertake research into oral contraception  Pincus confirmed that progesterone inhibits ovulation  First product called Enovid - 5 and 10 milligram dose

Answer 19

Human trials conducted in Massachusetts, US, and Puerto Rico  In Puerto Rico, women were not initially told what the Pill was meant to do  Women dropped out of the study due to severe side effects, but testing continued  Once women were told what the Pill was designed to do, they volunteered freely  However, they were not told they were part of a clinical trial of an experimental treatment  17% of participants reported serious side effects  3 women died, but were not autopsied to check for correlation with Pill use  Dr. Edris Rice-Wray, medical director of the Puerto Rico Family Planning Association, said that Pill was not safe to use in its current formula  Pill was nonetheless released by Searle & Co.

Answer 20

 Most oral contraceptive formulations contain a combination of synthetic oestrogen and progestogen (ethinylestradiol and progestin/s).  The quantities and proportions can vary, and some contain progestin only.  Progestins are steroids, and bind to steroid receptors in the brain, as well as to the sex hormone binding globuline (SHG).  They can affect blood glucose levels, lipid levels, and can stimulate other hormone production in the body.  Older progestins could stimulate androgens (masculinising hormones), whereas modern progestins are anti-androgenic.  However, research into hormonal contraception’s effects on the brain is still scanty.

Answer 21

Oestrogen inhibits the pituitary gland’s secretion of FollicleStimulating Hormone (FSH), and so suppresses the development of follicles containing eggs on the ovary.  Meanwhile, progestogen works at the same time to inhibit the pituitary gland’s production of luteinising hormone (LH), another hormone which helps to produce egg follicles.  Progestogen also changes the cervical mucus, which impedes sperm movement.  Because no modern hormonal contraceptive formula completely suppresses ovulation 100% of the time, hormonal contraception also works to prevent implantation.  Both oestrogen and progestogen work together to affect the ability of the Fallopian tubes to collect and move a fertilised gamete  They change the womb lining (endometrium) so that a fertilised gamete will not attach or implant.

Answer 22

 1962: G D Searle & Co (manufacturer) received reports of 132 cases of blood clots in Pill users  11 cases resulted in death  Searle denied that the Pill caused deaths  Food and Drug Administration (FDA) assured doctors the drug was safe

Answer 23

Some doctors were not fully informed of the Pill’s dangers.  Some doctors did not consider it necessary to inform female patients about risks of Pill.  1970 US Gallup poll: two-thirds of the women surveyed said that their doctors had never warned them about risks of the Pill.  Complications arising from the Pill were rare enough for some doctors to believe that the benefit was worth the risk for their female patients.

Answer 24

Anecdotally, women’s health complaints were brushed aside or trivialised  Multiple health providers: eg. depression = psychiatrist; stroke = neurologist  Lack of proper medical history-taking and information-sharing  Took 10 years from Pill's initial approval to prove the statistical link between serious health risks and oral contraceptives

Answer 25

Pill approved by FDA on the grounds of ‘safety’ – but the ‘danger’ in this case was pregnancy  The Pill only met the FDA safety requirement because it was so effective at preventing pregnancy  This was considered sufficient to offset possible risk factors such as blood clots, strokes and death  Pill was approved prior to revelations about the dangers of thalidomide and prior to passage of the 1962 Drug Amendments in US  By 1960, Searle making $37 million a year from prescriptions

Answer 26

Women disrupted the hearings in protest at the lack of evidence taken directly from Pill users  Also angry at the consistent presentation of evidence that the Pill had known risks which were not explained to women prescribed it  Outcome: U.S. government introduced the ‘patient information sheet’, with complete information on side effects in every package of birth control pills sold.

Answer 27

Post-1970: hormone levels in the Pill were lowered to a fraction of the original doses  Discontinued 1998  Smaller hormone doses meant fewer side-effects  Also increased risk of unplanned pregnancy

Answer 28

 Metal intrauterine devices – IUDs - had been used as contraceptive inserts since the early 1900s.  Stimulate an immune response which makes uterus averse to implantation; copper IUDs are also spermicidal.  Hormonal IUDs slowly release progestins to limit ovulation.  Development of silicone during WWII led to silicon rod experimentation as a form of drug delivery.  Progestin-delivering silicon rods were first used in the US from the early 1980s.  Depo Provera (progestin-type long-acting injection) introduced in 1959 in the US and approved for contraceptive purposes in 1992.  In the 1960s, researchers in the US and Europe began investigating methods of administering medications and steroids through the vagina with a plastic ring.  The NuvaRing was one of the first monthly vaginal rings used for contraception - provides a self-administered method of birth control which can be more accessible for some users.

Answer 29

The research literature on oral contraception-related deaths is nonconclusive.  However, this could be affected by medical or coronial unwillingness to attribute deaths to the Pill:  Death of Maria Santa, aged 17, 2016, UK  Experienced massive headaches and sought medical attention 4 times  Died of blood clot on brain two days after collapsing  Two doctors testified to inquest that blood clot was probably caused by oral contraceptive  BUT: coroner Simon Nelson recorded a conclusion of death by natural causes  Off-label prescription may also affect recording of deaths caused by Pill-type medications.  Risks of CVD deaths / blood clots increase with a combination of the Pill and smoking.

Answer 30

Skovlund et al (2016), Association of hormonal contraception with depression, JAMA Psychiatry. (September 28, 2016; doi:10.1001/jamapsychiatry.2016.2387) de Wit et al (2021). Hormonal contraceptive use and depressive symptoms: systematic review and network meta-analysis of randomised trials. BJPsych open, 7(4), e110. https://doi.org/10.1192/bjo.2021.64

Answer 31

 1953: Australian doctor John Billings discovered link between cervical mucus states and fertility in women.  Developed first ‘fertility awareness’ approach to conception and contraception.  ‘Fertility awareness’ combines calendar and observation of physiological signs of fertility to avoid intercourse at fertile times:  Elevated basal body temperature on waking  Cervical mucus state (‘egg white’ = highly fertile)  Sexual desire  Front breast tenderness  Physical symptoms: headaches, constipation, gas, bloating  Mittelschmerz (ovulation pain; usually unilateral; sharp or dull)

Answer 32

 We 'are' our hormones.  Women's bodies are still not well understood by medical science.  Hormonal contraceptives change many aspects of women's lives and their perceptions.  How does the Pill affect mate selection?

Answer 33

 dimethandrolone undecanoate (DMAU) and 11-β methyl nortestosterone dodecylcarbonate ( 11βMNTDC)  These are progestogenic-androgens - single molecules with two functions.  The progestogenic function should lower pituitary production of gonadotropin hormones (FSH and LH) - like the Pill in women.  Inhibiting LH leads to lower testosterone in the testis – theoretically, sperm production should be inhibited by this.  The androgenic function supports sexual and other bodily functions in men that need adequate testosterone levels.  These progestogenic-androgens have good oral bioavailability = a single daily pill is possible.

Answer 34

 December 2023:YourChoice Therapeutics, Inc. began dosing male volunteers in a Phase One clinical study of YCT-529, a drug candidate designed to offer the first hormone-free male birth control pill.  Retinoic acid receptor-alpha (RAR-alpha) inhibitor -YCT-529 prevents sperm production by blocking access to vitamin A.  YCT-529 was 99% effective in preventing mouse pregnancies and decreasing monkey sperm counts after two weeks of dosing.  Fully reversible in animal models.

Answer 35

 Attempts to prevent unwanted pregnancy are as old as humanity.  External- and internal-use products developed in the early 20th century were more effective than primitive methods.  The Pill was the first chemical attempt to suppress ovulation.  The Pill was tested and approved under questionable conditions  There are known serious side-effects to the use of the Pill which are considered less risky than pregnancy.  What's happening with hormonal contraception today?

Hormonal Drugs Flashcards

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